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García-Gorrita C, Soriano JM, Merino-Torres JF, San Onofre N. Anthropometric Trajectories and Dietary Compliance During a Personalized Ketogenic Program. Nutrients 2025; 17:1475. [PMID: 40362784 PMCID: PMC12073587 DOI: 10.3390/nu17091475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 04/22/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND/OBJECTIVES Ketogenic diets (KDs) have gained attention for their potential to promote weight loss and metabolic improvements. However, data on long-term body composition changes and adherence rates in real-world settings remain limited. OBJECTIVE This study aimed to assess the effects of a personalized ketogenic dietary program on anthropometric parameters over a 9-month period and to evaluate adherence across time. METHODS A total of 491 adults participated in a longitudinal intervention involving a structured ketogenic nutrition plan with follow-up at 3, 6, and 9 months. Body weight, fat mass (FM), skeletal muscle mass (SMM), and other composition metrics were measured at each visit. RESULTS Significant reductions in body weight (-12.6 kg) and fat mass (-10.3 kg) were observed after 3 months (p < 0.001), with minimal changes at 6 months and partial regain by Month 9. SMM remained relatively stable throughout the study. Retention dropped substantially after 3 months, dropping from 487 to 115 participants at Month 6 and 41 at Month 9. Despite this, participants who completed the program maintained significant anthropometric improvements. CONCLUSIONS A well-formulated ketogenic diet may promote rapid fat loss while preserving lean mass in the short term. However, long-term adherence poses significant challenges. Strategies to enhance dietary sustainability and retention are essential for maximizing the benefits of KDs in clinical practice.
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Affiliation(s)
- Cayetano García-Gorrita
- Food & Health Lab, Institute of Materials Science, University of Valencia, 46980 Paterna, Spain;
| | - Jose M. Soriano
- Food & Health Lab, Institute of Materials Science, University of Valencia, 46980 Paterna, Spain;
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, University of Valencia-Health Research Institute La Fe, 46026 Valencia, Spain;
| | - Juan F. Merino-Torres
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, University of Valencia-Health Research Institute La Fe, 46026 Valencia, Spain;
- Department of Medicine, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
- Department of Endocrinology and Nutrition, University and Polytechnic Hospital La Fe, 46026 Valencia, Spain
| | - Nadia San Onofre
- NUTRALiSS Research Group, Faculty of Health Sciences, Universitat Oberta de Catalunya, Rambla del Poblenou 156, 08018 Barcelona, Spain;
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Sandby K, Krarup T, Chabanova E, Geiker NRW, Magkos F. Liver Fat Accumulation Is Associated With Increased Insulin Secretion Independent of Total, Visceral, and Pancreatic Fat. J Clin Endocrinol Metab 2025; 110:e1395-e1403. [PMID: 39150984 DOI: 10.1210/clinem/dgae572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/15/2024] [Accepted: 08/14/2024] [Indexed: 08/18/2024]
Abstract
CONTEXT Studies in heterogeneous groups of people with respect to sex, body mass index (BMI), and glycemic status (normoglycemia, impaired glucose tolerance, diabetes), indicate no relationship between liver fat accumulation and pancreatic insulin secretion. OBJECTIVE This work aimed to better understand the association of liver fat with insulin secretion. METHODS A cross-sectional analysis was conducted of 61 men with abdominal obesity who had high liver fat (HLF, ≥ 5.6% by magnetic resonance spectroscopy, n = 28) or low liver fat (LLF, n = 33), but were balanced on BMI, total body fat, visceral adipose tissue (VAT), and pancreatic fat. A frequently sampled 5-hour oral glucose tolerance test with 11 samples, in conjunction with mathematical modeling, was used to compute indices of insulin sensitivity and insulin secretion (oral minimal model). RESULTS Compared to individuals with LLF, those with HLF had significantly greater fasting glucose, insulin, C-peptide, and triglycerides; lower high-density lipoprotein cholesterol; but similar glycated hemoglobin A1c. Areas under the 5-hour curve for glucose, insulin, and C-peptide were greater in the HLF group than the LLF group (by ∼10%, ∼38%, and ∼28%, respectively); fasting and total postprandial insulin secretion rates were approximately 37% and approximately 50% greater, respectively (all P < .05); whereas the insulinogenic index was not different. HLF participants had lower whole-body and hepatic insulin sensitivity, disposition index, and total insulin clearance than LLF participants (all P < .05). CONCLUSION Accumulation of liver fat is associated with increased insulin secretion independently of total adiposity, abdominal fat distribution, and pancreatic fat. Thereby, hyperinsulinemia in fatty liver disease is partly because of insulin hypersecretion and partly because of impaired insulin clearance.
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Affiliation(s)
- Karoline Sandby
- Department of Nutrition, Exercise and Sports, University of Copenhagen, 1958 Frederiksberg C, Denmark
| | - Thure Krarup
- Department of Nutrition, Exercise and Sports, University of Copenhagen, 1958 Frederiksberg C, Denmark
- Department of Endocrinology, Copenhagen University Hospital Bispebjerg and Frederiksberg, 2400 Copenhagen NV, Denmark
| | - Elizaveta Chabanova
- Department of Radiology, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark
| | - Nina R W Geiker
- Department of Nutrition, Exercise and Sports, University of Copenhagen, 1958 Frederiksberg C, Denmark
- Centre for Childhood Health, 2300 Islands Brygge, Denmark
| | - Faidon Magkos
- Department of Nutrition, Exercise and Sports, University of Copenhagen, 1958 Frederiksberg C, Denmark
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Wang ZZ, Ma GL, Xu B, Chen X, Yang BW, Qin XK, Duan WL, Feng MS, Yin H, Sun K, Zhu LG. Association between A body shape index and bone mineral density in middle-aged and elderly adults: a retrospective analysis of NHANES 2005-2018. Front Endocrinol (Lausanne) 2025; 16:1506841. [PMID: 40260279 PMCID: PMC12009725 DOI: 10.3389/fendo.2025.1506841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 03/20/2025] [Indexed: 04/23/2025] Open
Abstract
Introduction Despite accumulating evidence on central obesity and osteoporosis, the role of a body shape index (ABSI), a nonlinear index quantifying body shape via body mass index (BMI), waist circumference (WC), and height, remains controversial and underexplored. Although recent meta-analyses suggest central obesity may modulate fracture risk bidirectionally, no research has comprehensively compared ABSI with traditional adiposity metrics, such as BMI, WC, and waist-to-height ratio (WHtR), to predict site-specific changes in bone mineral density (BMD) across anatomical regions. Methods This study utilized National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018, involving 12,421 participants. ABSI was computed using the formula: ABSI = WC/(BMI²/³ × Height¹/²). BMD was assessed at four sites-the total femur (TF), femoral neck (FN), trochanter (TR), and intertrochanter (IN) regions-via dual-energy X-ray absorptiometry (DXA). The association between ABSI and BMD was analyzed via multiple regression models and a generalized additive model (GAM). To compare ABSI's predictive efficacy with conventional adiposity indices, regression analyses juxtaposed ABSI against BMI, WC, and WHtR in assessing correlations with site-specific BMD. Results After full covariate adjustment, a significant negative association was observed between ABSI and BMD in four femoral regions (P< 0.01). Smoothed curve fitting revealed a significant nonlinear relationship and threshold effect between ABSI and BMD among middle-aged and older individuals. Additionally, an inverted J-shaped curve was observed between ABSI and BMD in all four femoral regions. Meanwhile, ABSI showed significant negative associations with BMD across all femoral sites (β = -0.27 to -0.31, p-trend< 0.000001), whereas BMI, WC, and WHtR exhibited positive correlations (WHtR showing the strongest effect: β = 0.41-0.69). This highlights ABSI's ability to detect central adiposity-related bone loss obscured by conventional obesity metrics. Conclusion ABSI's robust inverse associations with femoral BMD (β = -0.27 to -0.31), persisting across nonlinear threshold analyses, establish it as a novel biomarker of central adiposity-related skeletal fragility. Unlike conventional indices reflecting mechanical loading benefits (BMI β = 0.008-0.012; WC β = 0.003-0.005; WHtR β = 0.41-0.69), ABSI specifically captures visceral fat-driven metabolic disorder-a critical pathway for osteoporosis risk stratification in normal-weight and obese populations.
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Affiliation(s)
- Zhi-Zhuang Wang
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guo-Liang Ma
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Bo Xu
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xin Chen
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Bo-Wen Yang
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiao-Kuan Qin
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wei-Li Duan
- Nanyang Hospital, Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine (Dushan Hospital District), Henan, China
- Nanyang Key Laboratory of Orthopedic Biomechanics of Traditional Chinese Medicine, Henan, China
| | - Min-Shan Feng
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - He Yin
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Kai Sun
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Li-Guo Zhu
- Department of Spine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Bone Setting Technology of Traditional Chinese Medicine, Beijing, China
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Gao X, Wang T, Li J, Li W, Zhu L, Zhu S, Song Z, Li P. Effect of Roux-en-Y gastric bypass on patients with type 2 diabetes mellitus and body mass index of 27.5-35 kg/m 2-a single center retrospective cohort study. BMC Surg 2025; 25:135. [PMID: 40186119 PMCID: PMC11969988 DOI: 10.1186/s12893-025-02879-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 03/26/2025] [Indexed: 04/07/2025] Open
Abstract
INTRODUCTION While Roux-en-Y gastric bypass (RYGB) has been extensively studied in patients with type 2 diabetes mellitus (T2DM) and preserved islet function, the significance of insulin resistance in guiding RYGB treatment remains unclear. This study aimed to evaluate the efficacy of RYGB in T2DM patients with a low body mass index (BMI, 27.5-35 kg/m²), insulin resistance, and impaired β-cell function. METHODS A retrospective cohort of 34 T2DM patients with low BMI who underwent RYGB at our institution was analyzed. Insulin resistance was assessed using hyperinsulinemic euglycemic clamp. The indicators related to glucose and lipid metabolism were also assessed and collected at baseline and 12 months postoperatively. RESULTS Significant reductions in BMI and HbA1c were observed within 12 months post-surgery (P < 0.05). Fasting plasma glucose decreased from 9.40 ± 3.12 mmol/L to 5.87 ± 2.67 mmol/L (P < 0.05). Complete remission rates were 31.25% for T2DM, 100% for hypertriglyceridemia, and 70% for hypertension. Multivariable logistic analysis identified shorter diabetes duration (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.83-0.95, P = 0.025), higher BMI (OR 1.14, 95% CI 1.06-1.34, P = 0.033), and lower peripheral glucose disposal rate (OR 0.95, 95% CI 0.93-0.97, P = 0.043) as independent predictors of diabetes remission. CONCLUSIONS Patients with T2DM and low BMI who have insulin resistance may still benefit from RYGB, even if they exhibit impaired β cell function. Shorter duration of diabetes, higher BMI and lower peripheral glucose disposal rate were independent predictors of diabetes remission after RYGB.
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Affiliation(s)
- Xiang Gao
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Tao Wang
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Jiahao Li
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Weizheng Li
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Liyong Zhu
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Shaihong Zhu
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Zhi Song
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
| | - Pengzhou Li
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
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Warmke N, Bridge KI, Ozber CH, Smith J, Platt F, Haywood NJ, Skromna A, Makava N, Yuldasheva NY, Wheatcroft S, Kearney MT, Cubbon RM, Griffin KJ. Insulin receptor signalling in PDGFRβ-expressing cells influences systemic metabolism and negatively impacts lipid storage. Biochem Biophys Res Commun 2024; 735:150799. [PMID: 39406023 DOI: 10.1016/j.bbrc.2024.150799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 09/19/2024] [Accepted: 10/07/2024] [Indexed: 11/05/2024]
Abstract
Pericytes are vascular mural cells that support the microvasculature; their dysfunction contributes to diabetic retinopathy and has been linked to obesity in humans. To explore the role of pericyte insulin signalling on systemic metabolism we utilised male mice from our previously described PIR-/- (PIRKO) mouse line which has insulin receptor (Insr) knockout in PDGFRβ-expressing cells. These animals exhibit systemic insulin resistance from as early as 8-weeks of age, despite no change in body weight or activity level, and show altered body composition and hepatosteatosis. When challenged with high fat diet, PIR-/- remain insulin resistant but are protected from weight gain with reduced adipose tissue expansion across all depots and altered adipose morphology. Exhibiting parallels with the metabolically-obese-normal-weight (MONW) human phenotype, the PIR-/- line underlines the importance of pericyte biology in the development of both diabetes and obesity and establishes the angiopoietin (Ang)/Tie signalling pathway as a focus for future research.
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Affiliation(s)
- Nele Warmke
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Katherine I Bridge
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Claire H Ozber
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK; Leeds Institute of Medical Research at St James' Hospital, Faculty of Medicine and Health, University of Leeds, Beckett Street, LS9 7TF, UK
| | - Jessica Smith
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Fiona Platt
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Natalie J Haywood
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Anna Skromna
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Natallia Makava
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Nadira Y Yuldasheva
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Stephen Wheatcroft
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Mark T Kearney
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Richard M Cubbon
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
| | - Kathryn J Griffin
- Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
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Schulhof A, Frishman WH. Alternative Perspectives on Obesity and Hypertension. Cardiol Rev 2024:00045415-990000000-00353. [PMID: 39436088 DOI: 10.1097/crd.0000000000000802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2024]
Abstract
It is known that obesity and hypertension have a relationship with one another. Often, obesity is thought to directly cause hypertension, with a list of mechanisms commonly cited. This, however, does not do the relationship justice. Not only can the directionality of the relationship be flipped, but the mechanisms may be misattributed confounders, themselves. Beyond this, some argue that the results of trials using glucagon-like-peptide-1 receptor agonist (GLP1R) medications suggest a causal relationship between obesity and hypertension, but this will be debunked. The relationship is far from linear, and mainstream literature often excludes key confounders that will be discussed in this article including food insecurity, mental health, socioeconomic status (SES), and weight stigma and discrimination. The factors used to measure the risk of hypertension as well as the measurements of hypertension, itself, need to be reexamined. For instance, there may be a high amount of "false positives" among the diagnosed. Finally, current research needs to be critically evaluated for forms of weight centrism and weight bias, deciphering improper assumptions from true, evidence-based science.
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Affiliation(s)
- Atara Schulhof
- From the Departments of Cardiology and Medicine, New York Medical College, Westchester Medical Center, Valhalla, NY
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Essa BS, Meena MQ. Potential of Fasting C-peptide to Glucose Ratio and Triglyceride Glucose Index as Markers for β-Cell Dysfunction and Insulin Resistance in Patients With Type 2 Diabetes on Insulin Therapy. Cureus 2024; 16:e66543. [PMID: 39252700 PMCID: PMC11381477 DOI: 10.7759/cureus.66543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/09/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Pathogenesis of type 2 diabetes mellitus (T2DM) is combined from initial insulin resistance (IR) and subsequent β-cell dysfunction. Insulin therapy can replace β-cell function in advanced stages. However excessive insulin therapy increases IR and may expose the patients to risk of cardiovascular disease. We aim to assess β-cell function and IR in patients with type 2 diabetes on insulin therapy by fasting C-peptide to glucose ratio (FCPGR), and triglyceride glucose (TyG) index respectively to support treatment plans. METHOD A cross-sectional study was conducted at the Galiawa Diabetes and Endocrinology Teaching Center in Erbil City, Iraq, from June 2023 to January 2024. A convenient sample of 100 patients with T2DM on insulin-based therapy were included after obtaining informed written consent and excluding conditions such as acute illness, uncertain type of diabetes, etc. Each patient was evaluated for anthropometric parameters and current treatment details. Biochemical tests were then carried out to calculate metabolic syndrome (MetS) index score, FCPGR, and TyG index. Finally, patients were divided into four subgroups according to their FCPGR and TyG index and the data were analyzed statistically. RESULT The data showed those patients with sufficient β-cell function were 60 (60%), and patients with high TyG index were 95 (95%). There was a significant negative correlation between FCPGR and hemoglobin A1c (HbA1c) (p-value=0.001), while there was a positive correlation between TyG index and HbA1C (p-value=0.001). None of these markers were correlated with BMI (p-value=0.297, and 0.976), duration of T2DM (p-value=0.258, and 0.458), and dose of insulin therapy (p-value=0.901, and 0.477). Patients with sufficient β-cell function and high TyG index had the lowest HbA1C. CONCLUSION The study provides valuable insights into the utility of FCPGR and TyG index as biomarkers for β-cell function and insulin resistance in T2DM patients on insulin therapy. The significant correlation with HbA1C underscores their potential in clinical practice. However, the lack of correlation with BMI, disease duration, and insulin dose suggests that further investigation is needed to fully understand these biomarkers' implications across diverse patient profiles.
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Affiliation(s)
- Breshan S Essa
- Endocrinology and Diabetes, Ninawa Health Directorate, Mosul, IRQ
| | - Mohammed Q Meena
- Medicine, College of Medicine, Hawler Medical University, Erbil, IRQ
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Barbaro F, Conza GD, Quartulli FP, Quarantini E, Quarantini M, Zini N, Fabbri C, Mosca S, Caravelli S, Mosca M, Vescovi P, Sprio S, Tampieri A, Toni R. Correlation between tooth decay and insulin resistance in normal weight males prompts a role for myo-inositol as a regenerative factor in dentistry and oral surgery: a feasibility study. Front Bioeng Biotechnol 2024; 12:1374135. [PMID: 39144484 PMCID: PMC11321979 DOI: 10.3389/fbioe.2024.1374135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 07/01/2024] [Indexed: 08/16/2024] Open
Abstract
Background In an era of precision and stratified medicine, homogeneity in population-based cohorts, stringent causative entry, and pattern analysis of datasets are key elements to investigate medical treatments. Adhering to these principles, we collected in vivo and in vitro data pointing to an insulin-sensitizing/insulin-mimetic effect of myo-inositol (MYO) relevant to cell regeneration in dentistry and oral surgery. Confirmation of this possibility was obtained by in silico analysis of the relation between in vivo and in vitro results (the so-called bed-to-benchside reverse translational approach). Results Fourteen subjects over the 266 screened were young adult, normal weight, euglycemic, sedentary males having normal appetite, free diet, with a regular three-times-a-day eating schedule, standard dental hygiene, and negligible malocclusion/enamel defects. Occlusal caries were detected by fluorescence videoscanning, whereas body composition and energy balance were estimated with plicometry, predictive equations, and handgrip. Statistically significant correlations (Pearson r coefficient) were found between the number of occlusal caries and anthropometric indexes predicting insulin resistance (IR) in relation to the abdominal/visceral fat mass, fat-free mass, muscular strength, and energy expenditure adjusted to the fat and muscle stores. This indicated a role for IR in affecting dentin reparative processes. Consistently, in vitro administration of MYO to HUVEC and Swiss NIH3T3 cells in concentrations corresponding to those administered in vivo to reduce IR resulted in statistically significant cell replication (ANOVA/Turkey tests), suggesting that MYO has the potential to counteract inhibitory effects of IR on dental vascular and stromal cells turnover. Finally, in in silico experiments, quantitative evaluation (WOE and information value) of a bioinformatic Clinical Outcome Pathway confirmed that in vitro trophic effects of MYO could be transferred in vivo with high predictability, providing robust credence of its efficacy for oral health. Conclusion Our reverse bed-to-benchside data indicate that MYO might antagonize the detrimental effects of IR on tooth decay. This provides feasibility for clinical studies on MYO as a regenerative factor in dentistry and oral surgery, including dysmetabolic/aging conditions, bone reconstruction in oral destructive/necrotic disorders, dental implants, and for empowering the efficacy of a number of tissue engineering methodologies in dentistry and oral surgery.
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Affiliation(s)
- Fulvio Barbaro
- Department of Medicine and Surgery - DIMEC, Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S.), Museum and Historical Library of Biomedicine - BIOMED, University of Parma, Parma, Italy
| | - Giusy Di Conza
- Department of Medicine and Surgery - DIMEC, Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S.), Museum and Historical Library of Biomedicine - BIOMED, University of Parma, Parma, Italy
| | - Francesca Pia Quartulli
- Department of Medicine and Surgery - DIMEC, Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S.), Museum and Historical Library of Biomedicine - BIOMED, University of Parma, Parma, Italy
| | - Enrico Quarantini
- Odontostomatology Unit, and R&D Center for Artificial Intelligence in Biomedicine and Odontostomatology (A.I.B.O), Galliera Medical Center, San Venanzio di Galliera, Italy
| | - Marco Quarantini
- Odontostomatology Unit, and R&D Center for Artificial Intelligence in Biomedicine and Odontostomatology (A.I.B.O), Galliera Medical Center, San Venanzio di Galliera, Italy
| | - Nicoletta Zini
- CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Unit of Bologna, Bologna, Italy
| | - Celine Fabbri
- Course on Odontostomatology, University Vita-Salute San Raffaele, Milan, Italy
| | - Salvatore Mosca
- Course on Disorders of the Locomotor System, Fellow Program in Orthopaedics and Traumatology, University Vita-Salute San Raffaele, Milan, Italy
| | - Silvio Caravelli
- O.U. Orthopedics Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Massimiliano Mosca
- O.U. Orthopedics Bentivoglio, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Paolo Vescovi
- Department of Medicine and Surgery - DIMEC, Odontostomatology Section, University of Parma, Parma, Italy
| | | | | | - Roberto Toni
- CNR - ISSMC, Faenza, Italy
- Academy of Sciences of the Institute of Bologna, Section IV - Medical Sciences, Bologna, Italy
- Endocrinology, Diabetes, and Nutrition Disorders Outpatient Clinic - OSTEONET (Osteoporosis, Nutrition, Endocrinology, and Innovative Therapies) and R&D Center A.I.B.O, Centro Medico Galliera, San Venanzio di Galliera, Italy
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Tufts Medical Center - Tufts University School of Medicine, Boston, MA, United States
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Cooper ID, Kyriakidou Y, Petagine L, Edwards K, Soto-Mota A, Brookler K, Elliott BT. Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females. Biomedicines 2024; 12:1553. [PMID: 39062126 PMCID: PMC11274887 DOI: 10.3390/biomedicines12071553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/08/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer's disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.5 kg/m2 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9 years) maintaining nutritional ketosis (NK) for an average of 3.9 years (± 2.3) who underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Ketosis suppression significantly increased insulin, 1.83-fold (p = 0.0006); glucose, 1.17-fold (p = 0.0088); homeostasis model assessment for insulin resistance (HOMA-IR), 2.13-fold (p = 0.0008); leptin, 3.35-fold (p = 0.0010); total osteocalcin, 1.63-fold (p = 0.0138); and uncarboxylated osteocalcin, 1.98-fold (p = 0.0417) and significantly decreased beta-hydroxybutyrate, 13.50-fold (p = 0.0012) and glucagon-like peptide-1 (GLP-1), 2.40-fold (p = 0.0209). Sustained NK showed no adverse health effects and may mitigate hyperinsulinemia. All biomarkers returned to basal P1 levels after removing the intervention for SuK, indicating that metabolic flexibility was maintained with long-term euketonaemia.
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Affiliation(s)
- Isabella D. Cooper
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (B.T.E.)
| | - Yvoni Kyriakidou
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (B.T.E.)
| | - Lucy Petagine
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (B.T.E.)
| | - Kurtis Edwards
- Cancer Biomarkers and Mechanisms Group, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK;
| | - Adrian Soto-Mota
- Metabolic Diseases Research Unit, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City 14080, Mexico;
- School of Medicine, Tecnologico de Monterrey, Mexico City 14380, Mexico
| | - Kenneth Brookler
- Retired former Research Collaborator, Aerospace Medicine and Vestibular Research Laboratory, Mayo Clinic, Scottsdale, AZ 85259, USA;
| | - Bradley T. Elliott
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (B.T.E.)
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10
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Chen Y, Feuerstahler L, Martinez-Steele E, Buckley JP, Liu SH. Phthalate mixtures and insulin resistance: an item response theory approach to quantify exposure burden to phthalate mixtures. JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY 2024; 34:581-590. [PMID: 36966251 PMCID: PMC10580272 DOI: 10.1038/s41370-023-00535-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 02/27/2023] [Accepted: 03/09/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND Molar sums are often used to quantify total phthalate exposure, but they do not capture patterns of exposure to multiple phthalates. OBJECTIVE To introduce an exposure burden score method for quantifying exposure to phthalate metabolites and examine the association between phthalate burden scores and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). METHODS We applied item response theory (IRT) to data from 3474 adults aged 20-60 years in the 2013-2018 National Health and Examination Survey (NHANES) to quantify latent phthalate exposure burden from 12 phthalate metabolites. We compared model fits of three IRT models that used different a priori groupings (general phthalate burden; low molecular weight (LMW) and high molecular weight (HMW) burdens; and LMW, HMW and DEHP burden), and used the best fitting model to estimate phthalate exposure burden scores. Regression models assessed the covariate-adjusted association between phthalate burden scores and HOMA-IR. We compared findings to those using molar sums. In secondary analyses, we examined how the IRT model could be used for data harmonization when a subset of participants are missing some phthalate metabolites, and accounted for measurement error of the phthalate burden scores in estimating associations with HOMA-IR through a resampling approach using plausible value imputation. RESULTS A three correlated factors model (LMW, HMW and DEHP burdens) provided the best fit. One interquartile range (IQR) increase in DEHP burden score was associated with 0.094 (95% CI: 0.022, 0.164, p = 0.010) increase in log HOMA-IR, co-adjusted for LMW and HMW burden scores. Findings were consistent when using log molar sums. Associations of phthalate burden and insulin resistance were also consistent when participants were simulated to be missing some phthalate metabolites, and when we accounted for measurement error in estimating burden scores. CONCLUSION Both phthalate molar sums and burden scores are sensitive to associations with insulin resistance. Phthalate burden scores may be useful for data harmonization.
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Affiliation(s)
- Yitong Chen
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | - Jessie P Buckley
- Department of Environmental Health and Engineering, John Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Shelley H Liu
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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11
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Rakhmat II, Nugraha GI, Ariyanto EF, Pratiwi YS, Linasari D, Fatimah SN, Ghozali M, Syamsunarno MRAA, Akbar MR, Achmad TH. Strong Association of Metabolic Parameters with ADMA and VCAM-1 in Normo-Weight Subjects with Metabolic Syndrome. Diabetes Metab Syndr Obes 2024; 17:833-839. [PMID: 38406267 PMCID: PMC10888057 DOI: 10.2147/dmso.s448650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 02/11/2024] [Indexed: 02/27/2024] Open
Abstract
Background Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and is linked to obesity. Subjects with MetS who have normo-weight potentially show higher mortality and morbidity. Purpose This study aims to reveal the critical essential metabolic parameters associated with endothelial dysfunction in MetS subjects with normo-weight compared to obese. Patients and Methods The study was designed using a case-control approach. Ninety-nine MetS subjects (34 Normo-weight and 65 obese) from the urban population were enrolled in this study. The components of MetS are based on NCEP/ATP III criteria. Asymmetric dimethylarginine (ADMA) and vascular cell adhesion molecule 1 (VCAM-1) as markers for endothelial dysfunction were measured in both groups. Results Fasting blood glucose (FBG) levels were higher in the normo-weight group (143.38 ± 79.8 mg/dL) compared to the obese group (120.89 ± 46.5 mg/dL). High-density lipoprotein cholesterol (HDL-c) levels in the normo-weight group were lower (42.82 ± 10.1 mg/dL) compared to obesity (45.74 ± 9.3 mg/dL), while triacylglycerol (TAG) levels were higher in the obese (197.25 ± 110.5 mg/dL) compared to the normo-weight group (167.03 ± 98.4 mg/dL), although the differences were statistically not significant (all p > 0.05). The difference between ADMA and VCAM-1 levels was statistically not significant in both groups. Correlation between MetS components with endothelial dysfunction parameters shows that metabolic parameters correlate strongly. Interestingly, a stronger correlation between FBG and ADMA was observed in normo-weight (r = 0.519) compared to obese groups (r = 0.445). In addition, TAG consistently shows a significant correlation with ADMA and VCAM-1 in normo-weight groups. Conclusion Metabolic parameters, especially FBG and TAG, correlate strongly with endothelial dysfunction parameters in normo-weight subjects with metabolic syndrome.
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Affiliation(s)
- Iis Inayati Rakhmat
- Doctoral Study Program Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Biochemistry, Faculty of Medicine, Universitas Jenderal Achmad Yani, Cimahi, West Java, Indonesia
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
| | - Gaga Irawan Nugraha
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
| | - Eko Fuji Ariyanto
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
| | - Yuni Susanti Pratiwi
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
| | - Desy Linasari
- Department of Community Medicine, Faculty of Medicine, Universitas Jenderal Achmad Yani, Cimahi, West Java, Indonesia
| | - Siti Nur Fatimah
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
| | - Mohammad Ghozali
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
| | - Mas Rizky A A Syamsunarno
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
| | - Mohammad Rizki Akbar
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Padjadjaran-Hasan Sadikin General Hospital, Bandung, West Java, Indonesia
| | - Tri Hanggono Achmad
- Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia
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12
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Soto A, Spongberg C, Martinino A, Giovinazzo F. Exploring the Multifaceted Landscape of MASLD: A Comprehensive Synthesis of Recent Studies, from Pathophysiology to Organoids and Beyond. Biomedicines 2024; 12:397. [PMID: 38397999 PMCID: PMC10886580 DOI: 10.3390/biomedicines12020397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/04/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a widespread contributor to chronic liver disease globally. A recent consensus on renaming liver disease was established, and metabolic dysfunction-associated steatotic liver disease, MASLD, was chosen as the replacement for NAFLD. The disease's range extends from the less severe MASLD, previously known as non-alcoholic fatty liver (NAFL), to the more intense metabolic dysfunction-associated steatohepatitis (MASH), previously known as non-alcoholic steatohepatitis (NASH), characterized by inflammation and apoptosis. This research project endeavors to comprehensively synthesize the most recent studies on MASLD, encompassing a wide spectrum of topics such as pathophysiology, risk factors, dietary influences, lifestyle management, genetics, epigenetics, therapeutic approaches, and the prospective trajectory of MASLD, particularly exploring its connection with organoids.
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Affiliation(s)
- Allison Soto
- Department of Surgery, University of Illinois College of Medicine, Chicago, IL 60607, USA;
| | - Colby Spongberg
- Touro College of Osteopathic Medicine, Great Falls, MT 59405, USA
| | | | - Francesco Giovinazzo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
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13
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Zhang L, Vella A, Nair KS, Jensen MD. Characteristics of Normal Weight Insulin-Resistant Adults with Unfavorable Health Outcomes. Metab Syndr Relat Disord 2024. [PMID: 38227797 DOI: 10.1089/met.2023.0154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024] Open
Abstract
Background: Insulin resistance can be present in otherwise healthy, normal weight adults. Whether there are phenotype/sex-differences between normal weight insulin-resistant (NWIR) and normal weight insulin-sensitive (NWIS) Caucasians and whether there are differences in adverse health outcomes are unknown. Our goal was to define phenotypes and intermediate-term health outcomes of NWIR versus NWIS Caucasian adults. Methods: We analyzed data from 227 healthy volunteers body mass index 18 to <25.0 kg/m2 who underwent insulin clamp studies between January 1987 and January 2017 at Mayo Clinic to identify those in the top (NWIS, n = 56) and bottom (NWIR, n = 56) quartiles of insulin action. We compared the phenotypical characteristics and were able to collect medical records data for 80% of NWIS and 88% of NWIR to identify time to onset of hypertension, hyperglycemia, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and all cause death; the follow-up averaged 11 (4, 20) years. Results: Body fat was significantly greater and peak VO2 was significantly less in both NWIS than NWIR males and females. Only in females was abdominal subcutaneous fat by computed tomography significantly greater in NWIR than NWIS. In NWIR males high-density lipoprotein-cholesterol and fat free mass were significantly less, and fasting insulin was greater than NWIS males. For the entire NWIS population, Kaplan-Meier disease-free survival analysis showed longer times free of hypertension, hyperglycemia, and some cardiovascular diseases than for NWIR. Conclusions: There are sex-specific phenotypes of NWIR in Caucasian adults. NWIR may be associated with accelerated onset of some adverse medical outcomes.
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Affiliation(s)
- Lili Zhang
- Division of Endocrinology, Department of Medicine, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA
| | - Adrian Vella
- Division of Endocrinology, Department of Medicine, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA
| | - K Sreekumaran Nair
- Division of Endocrinology, Department of Medicine, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael D Jensen
- Division of Endocrinology, Department of Medicine, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA
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14
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Blackmore K, Houchen CJ, Simonyan H, Arestakesyan H, Stark AK, Dow SA, Kim HR, Jeong JK, Popratiloff A, Young CN. A forebrain-hypothalamic ER stress driven circuit mediates hepatic steatosis during obesity. Mol Metab 2024; 79:101858. [PMID: 38141847 PMCID: PMC10809102 DOI: 10.1016/j.molmet.2023.101858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 10/25/2023] [Accepted: 12/19/2023] [Indexed: 12/25/2023] Open
Abstract
OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) affects 1 in 3 adults and contributes to advanced liver injury and cardiometabolic disease. While recent evidence points to involvement of the brain in NAFLD, the downstream neural circuits and neuronal molecular mechanisms involved in this response, remain unclear. Here, we investigated the role of a unique forebrain-hypothalamic circuit in NAFLD. METHODS Chemogenetic activation and inhibition of circumventricular subfornical organ (SFO) neurons that project to the paraventricular nucleus of the hypothalamus (PVN; SFO→PVN) in mice were used to study the role of SFO→PVN signaling in NAFLD. Novel scanning electron microscopy techniques, histological approaches, molecular biology techniques, and viral methodologies were further used to delineate the role of endoplasmic reticulum (ER) stress within this circuit in driving NAFLD. RESULTS In lean animals, acute chemogenetic activation of SFO→PVN neurons was sufficient to cause hepatic steatosis in a liver sympathetic nerve dependent manner. Conversely, inhibition of this forebrain-hypothalamic circuit rescued obesity-associated NAFLD. Furthermore, dietary NAFLD is associated with marked ER ultrastructural alterations and ER stress in the PVN, which was blunted following reductions in excitatory signaling from the SFO. Finally, selective inhibition of PVN ER stress reduced hepatic steatosis during obesity. CONCLUSIONS Collectively, these findings characterize a previously unrecognized forebrain-hypothalamic-ER stress circuit that is involved in hepatic steatosis, which may point to future therapeutic strategies for NAFLD.
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Affiliation(s)
- Katherine Blackmore
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Claire J Houchen
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Hayk Simonyan
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Hovhannes Arestakesyan
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Alyssa K Stark
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Samantha A Dow
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Han Rae Kim
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Jin Kwon Jeong
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA
| | - Anastas Popratiloff
- Nanofabrication and Imaging Center, George Washington University, Washington, DC, 20037, USA
| | - Colin N Young
- Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.
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15
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Almuraikhy S, Doudin A, Domling A, Althani AAJF, Elrayess MA. Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals. J Cell Mol Med 2024; 28:e18015. [PMID: 37938877 PMCID: PMC10805515 DOI: 10.1111/jcmm.18015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 11/10/2023] Open
Abstract
Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.
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Affiliation(s)
- Shamma Almuraikhy
- Biomedical Research CenterQatar UniversityDohaQatar
- Groningen Research Institute of Pharmacy, Drug DesignGroningen UniversityGroningenThe Netherlands
| | - Asmaa Doudin
- Biomedical Research CenterQatar UniversityDohaQatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug DesignGroningen UniversityGroningenThe Netherlands
| | - Asmaa Ali J. F. Althani
- Biomedical Research CenterQatar UniversityDohaQatar
- Department of Biomedical Sciences, College of Health Science, QU HealthQatar UniversityDohaQatar
| | - Mohamed A. Elrayess
- Biomedical Research CenterQatar UniversityDohaQatar
- College of Pharmacy, QU HealthQatar UniversityDohaQatar
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16
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Domouzoglou EM, Vlahos AP, Papafaklis MI, Cholevas VK, Chaliasos N, Siomou E, Michalis LK, Tsatsoulis A, Naka KK. Role of FGF21 and Leptin for the Diagnosis of Metabolic Health in Children with and without Obesity. J Pers Med 2023; 13:1680. [PMID: 38138907 PMCID: PMC10744927 DOI: 10.3390/jpm13121680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/27/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023] Open
Abstract
Obesity and unfavorable metabolic profiles increase the risk for cardiovascular complications in adults. Although it is important to distinguish different metabolic health states at an early stage, there are limited data on the related value of biomarkers in childhood. We aimed to identify biomarkers for the detection of different metabolic health states in children with and without obesity. The serum levels of metabolic regulators (fibroblast growth factor 21 [FGF21], leptin, adiponectin and insulin-like growth factor binding protein 1) and vascular indices (flow-mediated dilation [FMD] and carotid intima-media thickness) were assessed in 78 children. Differences between the metabolically healthy and unhealthy state within children with normal weight (MHN vs. MUN), and within children with overweight/obesity (MHO vs. MUO) were investigated; the discriminatory power of the biomarkers was studied. Both MUN and MUO groups expressed altered lipid and glucose homeostasis compared to their healthy counterparts. The metabolic unhealthy state in children with normal weight was linked to higher FGF21 levels which had good discriminatory ability (area under the curve [AUC]: 0.71, 95% CI: 0.54-0.88; p = 0.044). In overweight/obese children, leptin was increased in the metabolically unhealthy subgroup (AUC: 0.81, 95% CI: 0.68-0.95; p = 0.01). There was a decrease in FMD indicating worse endothelial function in overweight/obese children versus those with normal weight. Distinct states of metabolic health exist in both children with normal weight and overweight/obese children. FGF21 and leptin may help to identify the metabolic unhealthy state in children with normal weight and in overweight/obese children, respectively, early in life.
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Affiliation(s)
- Eleni M. Domouzoglou
- Child Health Department, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece
| | - Antonios P. Vlahos
- Child Health Department, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece
| | - Michail I. Papafaklis
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece; (M.I.P.); (K.K.N.)
| | - Vasileios K. Cholevas
- Child Health Department, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece
| | - Nikolaos Chaliasos
- Child Health Department, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece
| | - Ekaterini Siomou
- Child Health Department, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece
| | - Lampros K. Michalis
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece; (M.I.P.); (K.K.N.)
| | - Agathocles Tsatsoulis
- Department of Endocrinology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece
| | - Katerina K. Naka
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Stavrou Niarchou, 45110 Ioannina, Greece; (M.I.P.); (K.K.N.)
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17
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Pelczyńska M, Miller-Kasprzak E, Piątkowski M, Mazurek R, Klause M, Suchecka A, Bucoń M, Bogdański P. The Role of Adipokines and Myokines in the Pathogenesis of Different Obesity Phenotypes-New Perspectives. Antioxidants (Basel) 2023; 12:2046. [PMID: 38136166 PMCID: PMC10740719 DOI: 10.3390/antiox12122046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/19/2023] [Accepted: 11/25/2023] [Indexed: 12/24/2023] Open
Abstract
Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.
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Affiliation(s)
- Marta Pelczyńska
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland; (E.M.-K.); (P.B.)
| | - Ewa Miller-Kasprzak
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland; (E.M.-K.); (P.B.)
| | - Marcin Piątkowski
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Roksana Mazurek
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Mateusz Klause
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Anna Suchecka
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Magdalena Bucoń
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Paweł Bogdański
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland; (E.M.-K.); (P.B.)
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18
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Jung S, Nam JY. Sex Differences Associated with Weekend Catch-Up Sleep and Waist-to-Height-Ratio among South Korean Adults Using Korea National Health and Nutrition Examination Survey 2016-2021 Data. Healthcare (Basel) 2023; 11:2889. [PMID: 37958033 PMCID: PMC10648526 DOI: 10.3390/healthcare11212889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/30/2023] [Accepted: 11/01/2023] [Indexed: 11/15/2023] Open
Abstract
The global surge in obesity rates is closely linked to the rise in sleep deprivation and prevalence of sleep disorders. This study aimed to investigate the association between weekend catch-up sleep (CUS) and obesity among Korean adults. Using multiple logistic regression analysis, we analyzed the data of 6790 adults aged >19 years obtained from the Korea National Health and Nutrition Examination Survey 2016-2021. In the subgroup analysis, we conducted multiple logistic regression analysis to determine the association between weekend CUS and obesity, stratified by sex. Women were significantly more likely to be obese than men (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.46-0.61). Obesity was associated with 1 ≤ weekend CUS < 2 (OR = 0.86, 95% CI = 0.75-0.99) but not with weekend CUS ≤ 0. Compared to men, women had a lower obesity risk when engaging in weekend supplementary sleep that was 1 ≤ weekend CUS < 2 (OR = 0.78, 95% CI = 0.63-0.97). Our findings revealed that weekend CUS was associated with obesity. Our findings suggest that weekend CUS may offer a form of biological protection against obesity, and they contribute to a better understanding of this association and may serve as a basis for better obesity management.
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Affiliation(s)
| | - Jin Young Nam
- Department of Healthcare Management, Eulji University, Seongnam-si 13135, Republic of Korea;
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Ding Y, Deng Q, Yang M, Niu H, Wang Z, Xia S. Clinical Classification of Obesity and Implications for Metabolic Dysfunction-Associated Fatty Liver Disease and Treatment. Diabetes Metab Syndr Obes 2023; 16:3303-3329. [PMID: 37905232 PMCID: PMC10613411 DOI: 10.2147/dmso.s431251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 10/10/2023] [Indexed: 11/02/2023] Open
Abstract
Obesity,and metabolic dysfunction-associated fatty liver disease (MAFLD) have reached epidemic proportions globally. Obesity and MAFLD frequently coexist and act synergistically to increase the risk of adverse clinical outcomes (both hepatic and extrahepatic). Type 2 diabetes mellitus (T2DM) is the most important risk factor for rapid progression of steatohepatitis and advanced fibrosis. Conversely, the later stages of MAFLD are associated with an increased risk of T2DM incident. According to the proposed criteria, MAFLD is diagnosed in patients with liver steatosis and in at least one in three: overweight or obese, T2DM, or signs of metabolic dysregulation if they are of normal weight. However, the clinical classification and correlation between obesity and MAFLD is more complex than expected. In addition, treatment for obesity and MAFLD are associated with a reduced risk of T2DM, suggesting that liver-based treatments could reduce the risk of developing T2DM. This review describes the clinical classification of obesity and MAFLD, discusses the clinical features of various types of obesity and MAFLD, emphasizes the role of visceral obesity and insulin resistance (IR) in the development of MAFLD,and summarizes the existing treatments for obesity and MAFLD that reduce the risk of developing T2DM.
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Affiliation(s)
- Yuping Ding
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Quanjun Deng
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Mei Yang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Haiyan Niu
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Zuoyu Wang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Shihai Xia
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
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Beyene HB, Giles C, Huynh K, Wang T, Cinel M, Mellett NA, Olshansky G, Meikle TG, Watts GF, Hung J, Hui J, Cadby G, Beilby J, Blangero J, Moses EK, Shaw JE, Magliano DJ, Meikle PJ. Metabolic phenotyping of BMI to characterize cardiometabolic risk: evidence from large population-based cohorts. Nat Commun 2023; 14:6280. [PMID: 37805498 PMCID: PMC10560260 DOI: 10.1038/s41467-023-41963-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 09/26/2023] [Indexed: 10/09/2023] Open
Abstract
Obesity is a risk factor for type 2 diabetes and cardiovascular disease. However, a substantial proportion of patients with these conditions have a seemingly normal body mass index (BMI). Conversely, not all obese individuals present with metabolic disorders giving rise to the concept of "metabolically healthy obese". We use lipidomic-based models for BMI to calculate a metabolic BMI score (mBMI) as a measure of metabolic dysregulation associated with obesity. Using the difference between mBMI and BMI (mBMIΔ), we identify individuals with a similar BMI but differing in their metabolic health and disease risk profiles. Exercise and diet associate with mBMIΔ suggesting the ability to modify mBMI with lifestyle intervention. Our findings show that, the mBMI score captures information on metabolic dysregulation that is independent of the measured BMI and so provides an opportunity to assess metabolic health to identify "at risk" individuals for targeted intervention and monitoring.
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Affiliation(s)
- Habtamu B Beyene
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
- Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia
- Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia
| | - Corey Giles
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia
- Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia
| | - Kevin Huynh
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia
- Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia
| | - Tingting Wang
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia
- Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia
| | - Michelle Cinel
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | | | | | - Thomas G Meikle
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia
| | - Gerald F Watts
- School of Medicine, University of Western Australia, Perth, WA, Australia
- Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, WA, Australia
| | - Joseph Hung
- School of Medicine, University of Western Australia, Perth, WA, Australia
| | - Jennie Hui
- PathWest Laboratory Medicine of Western Australia, Nedlands, WA, Australia
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- School of Population and Global Health, University of Western Australia, Crawley, WA, Australia
| | - Gemma Cadby
- School of Population and Global Health, University of Western Australia, Crawley, WA, Australia
| | - John Beilby
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
| | - John Blangero
- South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - Eric K Moses
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - Jonathan E Shaw
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Dianna J Magliano
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
| | - Peter J Meikle
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
- Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia.
- Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia.
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21
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Preda A, Carbone F, Tirandi A, Montecucco F, Liberale L. Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management. Rev Endocr Metab Disord 2023; 24:901-919. [PMID: 37358728 PMCID: PMC10492705 DOI: 10.1007/s11154-023-09813-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/31/2023] [Indexed: 06/27/2023]
Abstract
Obesity epidemic reached the dimensions of a real global health crisis with more than one billion people worldwide living with obesity. Multiple obesity-related mechanisms cause structural, functional, humoral, and hemodynamic alterations with cardiovascular (CV) deleterious effects. A correct assessment of the cardiovascular risk in people with obesity is critical for reducing mortality and preserving quality of life. The correct identification of the obesity status remains difficult as recent evidence suggest that different phenotypes of obesity exist, each one associated with different degrees of CV risk. Diagnosis of obesity cannot depend only on anthropometric parameters but should include a precise assessment of the metabolic status. Recently, the World Heart Federation and World Obesity Federation provided an action plan for management of obesity-related CV risk and mortality, stressing for the instauration of comprehensive structured programs encompassing multidisciplinary teams. In this review we aim at providing an updated summary regarding the different obesity phenotypes, their specific effects on CV risk and differences in clinical management.
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Affiliation(s)
| | - Federico Carbone
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy
- Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132, Genoa, Italy
| | - Amedeo Tirandi
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy
- Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132, Genoa, Italy
| | - Fabrizio Montecucco
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy.
- Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132, Genoa, Italy.
| | - Luca Liberale
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy
- Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132, Genoa, Italy
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22
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Longo M, Zatterale F, Spinelli R, Naderi J, Parrillo L, Florese P, Nigro C, Leone A, Moccia A, Desiderio A, Raciti GA, Miele C, Smith U, Beguinot F. Altered H3K4me3 profile at the TFAM promoter causes mitochondrial alterations in preadipocytes from first-degree relatives of type 2 diabetics. Clin Epigenetics 2023; 15:144. [PMID: 37679776 PMCID: PMC10486065 DOI: 10.1186/s13148-023-01556-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 08/14/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND First-degree relatives of type 2 diabetics (FDR) exhibit a high risk of developing type 2 diabetes (T2D) and feature subcutaneous adipocyte hypertrophy, independent of obesity. In FDR, adipose cell abnormalities contribute to early insulin-resistance and are determined by adipocyte precursor cells (APCs) early senescence and impaired recruitment into the adipogenic pathway. Epigenetic mechanisms signal adipocyte differentiation, leading us to hypothesize that abnormal epigenetic modifications cause adipocyte dysfunction and enhance T2D risk. To test this hypothesis, we examined the genome-wide histone profile in APCs from the subcutaneous adipose tissue of healthy FDR. RESULTS Sequencing-data analysis revealed 2644 regions differentially enriched in lysine 4 tri-methylated H3-histone (H3K4me3) in FDR compared to controls (CTRL) with significant enrichment in mitochondrial-related genes. These included TFAM, which regulates mitochondrial DNA (mtDNA) content and stability. In FDR APCs, a significant reduction in H3K4me3 abundance at the TFAM promoter was accompanied by a reduction in TFAM mRNA and protein levels. FDR APCs also exhibited reduced mtDNA content and mitochondrial-genome transcription. In parallel, FDR APCs exhibited impaired differentiation and TFAM induction during adipogenesis. In CTRL APCs, TFAM-siRNA reduced mtDNA content, mitochondrial transcription and adipocyte differentiation in parallel with upregulation of the CDKN1A and ZMAT3 senescence genes. Furthermore, TFAM-siRNA significantly expanded hydrogen peroxide (H2O2)-induced senescence, while H2O2 did not affect TFAM expression. CONCLUSIONS Histone modifications regulate APCs ability to differentiate in mature cells, at least in part by modulating TFAM expression and affecting mitochondrial function. Reduced H3K4me3 enrichment at the TFAM promoter renders human APCs senescent and dysfunctional, increasing T2D risk.
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Affiliation(s)
- Michele Longo
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Federica Zatterale
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Rosa Spinelli
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Jamal Naderi
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Luca Parrillo
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Pasqualina Florese
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy
| | - Cecilia Nigro
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Alessia Leone
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Augusta Moccia
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy
| | - Antonella Desiderio
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Gregory A Raciti
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy.
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy.
| | - Claudia Miele
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
| | - Ulf Smith
- Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Francesco Beguinot
- Department of Translational Medicine, Federico II University of Naples, Naples, Italy.
- URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy.
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23
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Kent DE, Jacob C, Kinney BM. Retrospective analysis of high-intensity focused electromagnetic procedure synchronized with radiofrequency energy for visceral fat reduction. J Cosmet Dermatol 2023; 22:2485-2491. [PMID: 37154787 DOI: 10.1111/jocd.15784] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 03/20/2023] [Accepted: 04/09/2023] [Indexed: 05/10/2023]
Abstract
BACKGROUND Visceral adipose tissue (VAT), present in the abdominal cavity, oftentimes contributes to an unpleasant aesthetic appearance and can be correlated with serious health issues. High-intensity focused electromagnetic field (HIFEM) technology with synchronized radiofrequency (RF) was recently used for abdominal body shaping through subcutaneous fat reduction and muscle growth. AIM This study aimed to assess the effect of HIFEM + RF technology on VAT tissue. METHODS Data of 16 men and 24 women (22-62 years, 21.2-34.3 kg/cm2 ) from the original study were retrospectively reviewed. All subjects received three 30-min HIFEM + RF abdominal treatments once weekly for three consecutive weeks. The VAT area was measured in the axial plane of MRI scans at two levels: L4-L5 vertebrae and 5 cm above this level. The VAT was identified, segmented, and calculated, yielding total area in square centimeters per scan at both specified levels. RESULTS By thoughtful review of the subject's post-treatment MRI scans, no other changes in the abdominal cavity were found except for VAT. The evaluation showed a VAT reduction of 17.8% (p < 0.001) on average at 3-month follow-up, maintaining the results up to 6 months (-17.3%). Averaging the values obtained from both measured levels, the VAT, occupied an area of 100.2 ± 73.3 cm2 at the baseline. At the 3-month follow-up, the subjects achieved an average reduction of 17.9 cm2 , preserving the results at 6 months (-17.6 ± 17.3 cm). CONCLUSION This retrospective analysis of MRI images objectively documented the effect of HIFEM + RF abdominal therapy on VAT. The data indicates considerable VAT reduction without serious adverse events following the HIFEM + RF procedure.
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Affiliation(s)
- David E Kent
- Skin Care Physicians of Georgia, Macon, Georgia, USA
| | - Carolyn Jacob
- Chicago Cosmetic Surgery and Dermatology, Chicago, Illinois, USA
| | - Brian M Kinney
- USC Keck School of Medicine, Los Angeles, California, USA
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24
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Ye J, Guo K, Li X, Yang L, Zhou Z. The Prevalence of Metabolically Unhealthy Normal Weight and Its Influence on the Risk of Diabetes. J Clin Endocrinol Metab 2023; 108:2240-2247. [PMID: 36916473 DOI: 10.1210/clinem/dgad152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 03/08/2023] [Accepted: 03/08/2023] [Indexed: 03/16/2023]
Abstract
CONTEXT Diabetes is a major health problem and metabolically unhealthy is an important risk factor. OBJECTIVE To conduct the first nationally representative study on epidemiological data of metabolically unhealthy normal weight (MUNW) focused only on nondiabetic subjects and determine the predictive effect on diabetes in China. METHODS A longitudinal study was conducted using data from the Rich Healthcare Group in China. Metabolic status was determined by the revised National Cholesterol Education Program Adult Treatment Panel III criteria, and individuals with 2 or more criteria were categorized as MUNW and diagnosed with metabolic syndrome (MetS) if they met 3 or more. RESULTS Of a total of 63 830 nondiabetic normal-weight individuals, 8935 (14.0%) were classified as MUNW and 1916 (3.00%) were diagnosed with MetS. After adjusting for potential confounders, individuals with MUNW had a greater diabetes risk (4.234, 95% CI 3.089-5.803) than those without MUNW during an average of 3.10 years of follow-up. Also, the multivariable-adjusted hazard ratios for developing diabetes were 3.069 (95% CI 1.790-5.263), 7.990 (95% CI 4.668-13.677), and 11.950 (95% CI 6.618-21.579) for participants with 1, 2, and 3 or more components, respectively, compared with those without any components. Further analyses suggested that the number of MetS components present is associated with the risk of diabetes, especially in metabolically unhealthy normal-weight young male adults. Multivariable-adjusted hazard ratios (95% CI) for incident diabetes among individuals with 1, 2, and at least 3 components were 4.45 (1.45-13.72), 9.82 (3.05-31.64), and 15.13 (3.70-61.84) for participants aged ≤44 years, and 3.55 (1.81-6.97), 8.52 (4.34-16.73), and 13.69 (6.51-28.77) for male participants, respectively. CONCLUSIONS The prevalence of MUNW is 14% in Chinese normal-weight nondiabetic individuals, and active intervention is necessary for this category of people. The presence of MUNW significantly increases the risk of diabetes, and the risk of diabetes is associated with the number of MetS components present in the patient.
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Affiliation(s)
- Jianan Ye
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Keyu Guo
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Lin Yang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, Second Xiangya Hospital of Central South University, Changsha, 410011, China
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25
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Lahav Y, Kfir A, Gepner Y. The paradox of obesity with normal weight; a cross-sectional study. Front Nutr 2023; 10:1173488. [PMID: 37360304 PMCID: PMC10287971 DOI: 10.3389/fnut.2023.1173488] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 05/23/2023] [Indexed: 06/28/2023] Open
Abstract
Objective To evaluate the prevalence of excessive adiposity among normal-weight individuals, and their cardiometabolic risk. Methods This cross-sectional study included 3,001 participants (ages 20-95, 52% men, BMI 28.0 ± 5.5 kg/m2) who completed an anthropometric evaluation, dual x-ray absorptiometry (DXA) scan to measure body composition, and cardiometabolic blood markers. Excess adiposity was defined as ≥25% for men and ≥ 35% for women. Results Of the entire study participants, 967 were in normal BMI (18.5-24.9 kg/m2) with a wide body fat distribution (4-49%). Of them, 26% of men and 38% of women were classified with excess adiposity. As compared to normal-weight lean participants, normal-weight obese men and women had higher triglycerides (76.5 ± 37.3 vs. 101.2 ± 50.3 mg/dL, p = 0.004 and 84 ± 44.2 vs. 101.4 ± 91.1 mg/dL, p = 0.030; respectively) and elevated low-density lipoprotein cholesterol (103.3 ± 31.7 vs. 119.6 ± 45.5 mg/dL, p = 0.011) and total cholesterol (171.5 ± 40.3 vs. 190.2 ± 39 mg/dL, p = 0.007) for men only. Among NWO, abdominal circumference was prevalent in 60% of the females with NWO (≥88 cm), but only in 4% of males (≥102 cm). Conclusion Higher adiposity, even within normal weight, increases cardiometabolic risk, and abdominal waist circumference misclassified obesity in normal-weight individuals. This study highlights the need for a body composition evaluation to determine cardiometabolic risk for adults with normal body weight.
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Bray GA. Beyond BMI. Nutrients 2023; 15:nu15102254. [PMID: 37242136 DOI: 10.3390/nu15102254] [Citation(s) in RCA: 88] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/04/2023] [Accepted: 05/06/2023] [Indexed: 05/28/2023] Open
Abstract
This review examined the origins of the concept of the BMI in the work of Quetelet in the 19th century and its subsequent adoption and use in tracking the course of the pandemic of obesity during the 20th century. In this respect, it has provided a valuable international epidemiological tool that should be retained. However, as noted in this review, the BMI is deficient in at least three ways. First, it does not measure body fat distribution, which is probably a more important guide to the risk of excess adiposity than the BMI itself. Second, it is not a very good measure of body fat, and thus its application to the diagnosis of obesity or excess adiposity in the individual patient is limited. Finally, the BMI does not provide any insights into the heterogeneity of obesity or its genetic, metabolic, physiological or psychological origins. Some of these mechanisms are traced in this review.
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Affiliation(s)
- George A Bray
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
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27
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Jovanović M, Kovačević S, Brkljačić J, Djordjevic A. Oxidative Stress Linking Obesity and Cancer: Is Obesity a 'Radical Trigger' to Cancer? Int J Mol Sci 2023; 24:ijms24098452. [PMID: 37176160 PMCID: PMC10179114 DOI: 10.3390/ijms24098452] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/24/2023] [Accepted: 05/01/2023] [Indexed: 05/15/2023] Open
Abstract
Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer cells. Other than the increased risk of cancer development, obese cancer patients experience higher mortality rates and reduced therapy efficiency as well. The fact that obesity is considered the second leading preventable cause of cancer prioritizes the research on the mechanisms connecting obesity to cancerogenesis and finding the solutions to break the link. Oxidative stress is integral at different stages of cancer development and advancement in obese patients. Hypocaloric, balanced nutrition, and structured physical activity are some tools for relieving this burden. However, the sensitivity of simultaneously treating cancer and obesity poses a challenge. Further research on the obesity-cancer liaison would offer new perspectives on prevention programs and treatment development.
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Affiliation(s)
- Mirna Jovanović
- Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
| | - Sanja Kovačević
- Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
| | - Jelena Brkljačić
- Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
| | - Ana Djordjevic
- Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
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28
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Almuraikhy S, Anwardeen N, Doudin A, Sellami M, Domling A, Agouni A, Al Thani AA, Elrayess MA. The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals. Int J Mol Sci 2023; 24:ijms24097816. [PMID: 37175541 PMCID: PMC10178125 DOI: 10.3390/ijms24097816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20-30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.
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Affiliation(s)
- Shamma Almuraikhy
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9713 AV Groningen, The Netherlands
| | - Najeha Anwardeen
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Asmma Doudin
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Maha Sellami
- Physical Education Department (PE), College of Education, Qatar University, Doha P.O. Box 2713, Qatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9713 AV Groningen, The Netherlands
| | - Abdelali Agouni
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Asmaa A Al Thani
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- Department of Biomedical Sciences, College of Health Science, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Mohamed A Elrayess
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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Watanabe K, Wilmanski T, Diener C, Earls JC, Zimmer A, Lincoln B, Hadlock JJ, Lovejoy JC, Gibbons SM, Magis AT, Hood L, Price ND, Rappaport N. Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention. Nat Med 2023; 29:996-1008. [PMID: 36941332 PMCID: PMC10115644 DOI: 10.1038/s41591-023-02248-0] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 02/02/2023] [Indexed: 03/23/2023]
Abstract
Multiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations and is a risk factor for multiple chronic diseases. Here we report an atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in body mass index (BMI), as well as multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program (Arivale). Machine learning model predictions of BMI from blood multiomics captured heterogeneous phenotypic states of host metabolism and gut microbiome composition better than BMI, which was also validated in an external cohort (TwinsUK). Moreover, longitudinal analyses identified variable BMI trajectories for different omics measures in response to a healthy lifestyle intervention; metabolomics-inferred BMI decreased to a greater extent than actual BMI, whereas proteomics-inferred BMI exhibited greater resistance to change. Our analyses further identified blood analyte-analyte associations that were modified by metabolomics-inferred BMI and partially reversed in individuals with metabolic obesity during the intervention. Taken together, our findings provide a blood atlas of the molecular perturbations associated with changes in obesity status, serving as a resource to quantify metabolic health for predictive and preventive medicine.
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Affiliation(s)
| | | | | | - John C Earls
- Institute for Systems Biology, Seattle, WA, USA
- Thorne HealthTech, New York, NY, USA
| | - Anat Zimmer
- Institute for Systems Biology, Seattle, WA, USA
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | | | | | | | - Sean M Gibbons
- Institute for Systems Biology, Seattle, WA, USA
- Department of Bioengineering, University of Washington, Seattle, WA, USA
- eScience Institute, University of Washington, Seattle, WA, USA
| | | | - Leroy Hood
- Institute for Systems Biology, Seattle, WA, USA
- Department of Bioengineering, University of Washington, Seattle, WA, USA
- Phenome Health, Seattle, WA, USA
- Department of Immunology, University of Washington, Seattle, WA, USA
- Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA, USA
| | - Nathan D Price
- Institute for Systems Biology, Seattle, WA, USA
- Thorne HealthTech, New York, NY, USA
- Department of Bioengineering, University of Washington, Seattle, WA, USA
- Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA, USA
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Verma A, Jha A, Alagorie AR, Sharma R. Association of anthropometric parameters as a risk factor for development of diabetic retinopathy in patients with diabetes mellitus. Eye (Lond) 2023; 37:303-308. [PMID: 35058601 PMCID: PMC9873787 DOI: 10.1038/s41433-022-01934-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 12/15/2021] [Accepted: 01/11/2022] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To study the relationship of body fat distribution in patients with diabetes mellitus (DM), and its long-term complications like diabetic retinopathy (DR), in Indian population. METHODS This was a prospective, cross-sectional observational study involving 1773 subjects diagnosed with DM and 1778 age and gender-matched individuals. The patients with DM were assessed for the presence and severity of DR. Severe non-proliferative DR and proliferative DR were categorised as sight threatening DR (STDR). Anthropometric parameters, i.e., neck circumference (NC); mid-upper arm circumference (MAC); waist circumference (WC); hip circumference (HC); mid-thigh circumference (MTC) and body mass index (BMI) were measured using standardised technique. RESULTS The mean age was 59.33 ± 9.32 for DM group, and 66.03 ± 11.04 for non-DM group. DM group showed significantly greater NC, WC, and MTC and significantly reduced MAC and weight. HC and BMI were comparable between the groups. There was a significant positive correlation of MAC and WC (with any level of DR) and MAC, WC, and weight (for STDR); and a significant negative correlation of HC and MTC (with any level of DR) and NC, HC, MTC, and BMI (for STDR). Multiple logistic regression analysis confirmed that WC was the single most important predictor for any level of DR and STDR. CONCLUSIONS Association of body fat distribution with DM and DR appears multifactorial. However, central obesity signified by waist circumference appears to be the significant risk related to the development of DR and STDR in Indian population.
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Affiliation(s)
- Aditya Verma
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, College Road 18, Chennai, 600006, India
| | - Ashok Jha
- Department of Ophthalmology, Military Hospital, Gaya, Bihar, 823005, India.
| | | | - Rishi Sharma
- Department of Ophthalmology, Military Hospital, Yol, Himachal Pradesh, 176052, India
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Kouda K, Fujita Y, Nakama C, Ohara K, Tachiki T, Tamaki J, Yura A, Moon JS, Kajita E, Imai N, Uenishi K, Iki M. Association between trunk-to-peripheral fat ratio and renal function in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study. Environ Health Prev Med 2023; 28:30. [PMID: 37183008 DOI: 10.1265/ehpm.22-00279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.
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Affiliation(s)
- Katsuyasu Kouda
- Department of Hygiene and Public Health, Kansai Medical University
| | - Yuki Fujita
- Center for Medical Education, Kindai University Faculty of Medicine
| | - Chikako Nakama
- Department of Hygiene and Public Health, Kansai Medical University
| | - Kumiko Ohara
- Department of Hygiene and Public Health, Kansai Medical University
| | | | - Junko Tamaki
- Department of Hygiene and Public Health, Faculty of Medicine, Osaka Medical and Pharmaceutical University
| | - Akiko Yura
- Department of Public Health, Kindai University Faculty of Medicine
| | | | | | - Nami Imai
- Department of Pharmaceutical and Medical Business Sciences, Nihon Pharmaceutical University
| | - Kazuhiro Uenishi
- Laboratory of Physiological Nutrition, Kagawa Nutrition University
| | - Masayuki Iki
- Department of Public Health, Kindai University Faculty of Medicine
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Xie CH, Chen LW, Lin CL, Hu CC, Chien CH. Serum Uric Acid but Not Ferritin Level Is Associated with Hepatic Fibrosis in Lean Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease: A Community-Based Study. J Pers Med 2022; 12:jpm12122009. [PMID: 36556230 PMCID: PMC9782820 DOI: 10.3390/jpm12122009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 11/27/2022] [Accepted: 12/01/2022] [Indexed: 12/09/2022] Open
Abstract
Elevated serum ferritin and uric acid levels are common in patients with fatty liver disease. This study assessed the association between serum ferritin and uric acid levels and liver fibrosis in subjects with lean metabolic dysfunction-associated fatty liver disease (MAFLD). This cross-sectional study used data from a community screening examination for metabolic syndrome from December 2018 to September 2019 at Keelung Chang Gung Memorial Hospital. Subjects with lean MAFLD were defined as those with a body mass index (BMI) < 23 kg/m2 and hepatic steatosis according to the MAFLD criteria. A total of 182 lean subjects were included and were divided into lean MAFLD and lean healthy groups. Serum ferritin and uric acid concentrations were positively correlated with liver fibrosis, regardless of whether FIB-4, APRI, or NFS were used as references. Univariate logistic regression analysis showed that age and uric acid were associated with advanced liver fibrosis. After adjusting for potential confounders, only uric acid level was statistically significant in predicting the advanced liver fibrosis (OR = 6.907 (1.111−42.94), p = 0.038) in the lean MAFLD group. We found that an elevated serum uric acid level is an independent factor associated with advanced liver fibrosis in lean MAFLD subjects by noninvasive fibrosis scores.
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Affiliation(s)
- Cheng-Han Xie
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
| | - Li-Wei Chen
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
- Community Medicine Research Center, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
- Correspondence: ; Tel.: +886-2-24313131 (ext. 6203); Fax: +886-2-24335342
| | - Chih-Lang Lin
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
- Community Medicine Research Center, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
| | - Ching-Chih Hu
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
- Community Medicine Research Center, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
| | - Cheng-Hung Chien
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
- Community Medicine Research Center, Chang-Gung Memorial Hospital and University, Keelung 204, Taiwan
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Kurşunoğlu NE, Sarer Yurekli BP. Endocrine disruptor chemicals as obesogen and diabetogen: Clinical and mechanistic evidence. World J Clin Cases 2022; 10:11226-11239. [PMID: 36387809 PMCID: PMC9649566 DOI: 10.12998/wjcc.v10.i31.11226] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/19/2022] [Accepted: 09/27/2022] [Indexed: 02/05/2023] Open
Abstract
Obesity is becoming an inevitable pandemic all over the world. The World Obesity Federation predicts in the 2022 World Obesity Atlas that one billion people worldwide, including 1 in 5 women and 1 in 7 men, will be living with obesity by 2030. Moreover, the prevalence of diabetes is increasing worldwide, and diabetes is becoming more of a public health problem. Increased insulin resistance due to obesity and deficiency in insulin secretion are the two main causes of type 2 diabetes mellitus (T2DM). An exogenous chemical or mixture of chemicals that interferes with any aspect of hormone action was defined as endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA), the first known EDC, was synthesized and was considered to be estrogenic. Global production of BPA has increased progressively from 5 to 8 million tons (MT) between 2010 and 2016. Furthermore, researchers estimated that the production should reach 10.2 MT by 2022. The human population is exposed to EDCs in daily life in such forms as pesticides/herbicides, industrial and household products, plastics, detergents, and personal care products. The term obesogen was used for chemicals that promote weight gain and obesity by increasing the number of adipocytes and fat storage in existing adipocytes, changing the energy balance, and finally regulating appetite and satiety. Besides the obesogenic effect, EDCs can cause T2DM through alteration in ß cell function and morphology and insulin resistance. In this review, we provide clinical and mechanistic evidence regarding EDCs as obesogen and diabetogen. However, those studies are not enough methodologically to indicate causality. In this respect, randomized clinical trials are needed to investigate the association between obesogen, diabetogen and the related metabolic clinical picture.
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Gao L, Zhang P, Wang Y, Zhang W, Zhao J, Liu Y, Liu J, He S. Relationship between body composition and bone mineral density in postmenopausal women with type 2 diabetes mellitus. BMC Musculoskelet Disord 2022; 23:893. [PMID: 36192772 PMCID: PMC9528089 DOI: 10.1186/s12891-022-05814-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 09/09/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The aim of the study were to analyze the lumbar volumetric bone mineral density (BMD), fat distribution and changes of skeletal muscle with quantitative computed tomography (QCT) in postmenopausal women with type 2 diabetes mellitus (T2DM), and to evaluate the relationship between body composition and BMD. METHODS One hundred seventy-seven postmenopausal women with T2DM and 136 postmenopausal women without diabetes were included in the study and were divided into two groups according to age, 50-65 years age group and over 65 years of age group. The lumbar BMD (L1-L3), visceral fat mass (VFM), visceral fat area (VFA), subcutaneous fat mass (SFM), subcutaneous fat area (SFA), psoas major mass (PMM) and psoas major area (PMA) of each group were compared. Univariable and multivariable linear regression analysis were used to analyze the contribution of each variable to BMD in postmenopausal women with T2DM. RESULTS In women aged 50-65, the patients in the T2DM group had higher body mass index (BMI), VFM, VFA, and SFM (p < 0.05), compared with non-T2DM group. Over 65 years old, the BMI, BMD, VFM, VFA, and SFM was found to be much higher in participants with T2DM than in non-T2DM group (p < 0.05). Compared with women aged in 50-65 years old, those over 65 years old had higher VFA and VFM and lower BMD (p < 0.05), whether in the T2DM group or the non-T2DM group. Age, VFA and VFM were negatively correlated with BMD (r = -0.590, p ≤ 0.001; r = -0.179, p = 0.017; r = -0.155, p = 0.040, respectively). After adjusting for age, VFM and VFA were no longer correlated with BMD. No correlations between fat distribution or psoas major muscle and BMD in postmenopausal women with T2DM were observed. CONCLUSIONS T2DM can affect abdominal fat deposition in postmenopausal women. Postmenopausal elderly women with diabetes have higher BMD than normal elderly women. There was no correlation between fat distribution or psoas major and BMD in postmenopausal women with diabetes mellitus.
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Affiliation(s)
- Lei Gao
- Department of CT/MRI, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China
| | - Ping Zhang
- Department of CT/MRI, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China
| | - Yan Wang
- Department of Endocrinology, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China.
| | - Wei Zhang
- Department of Radiology, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China.
| | - Jian Zhao
- Department of CT/MRI, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China
| | - Ying Liu
- Department of CT/MRI, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China
| | - Jing Liu
- Department of Radiology, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China
| | - Shaoqiang He
- Department of Radiology, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei Province, China
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AlMuraikhy S, Anwardeen N, Naeem A, Sellami M, Domling A, Agouni A, Elrayess MA. Comparing the Metabolic Profiles Associated with Fitness Status between Insulin-Sensitive and Insulin-Resistant Non-Obese Individuals. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph191912169. [PMID: 36231474 PMCID: PMC9564877 DOI: 10.3390/ijerph191912169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 05/27/2023]
Abstract
(1) Background: Young non-obese insulin-resistant (IR) individuals could be at risk of developing metabolic diseases including type 2 diabetes mellitus. The protective effect of physical activity in this apparently healthy group is expected but not well characterized. In this study, clinically relevant metabolic profiles were determined and compared among active and sedentary insulin-sensitive (IS) and IR young non-obese individuals. (2) Methods: Data obtained from Qatar Biobank for 2110 young (20-30 years old) non-obese (BMI ≤ 30) healthy participants were divided into four groups, insulin-sensitive active (ISA, 30.7%), insulin-sensitive sedentary (ISS, 21.4%), insulin-resistant active (IRA, 20%), and insulin-resistant sedentary (IRS, 23.3%), using the homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires. The effect of physical activity on 66 clinically relevant biochemical tests was compared among the four groups using linear models. (3) Results: Overall, non-obese IR participants had significantly (p ≤ 0.001) worse vital signs, blood sugar profiles, inflammatory markers, liver function, lipid profiles, and vitamin D levels than their IS counterparts. Physical activity was positively associated with left handgrip (p ≤ 0.01) and levels of creatine kinase (p ≤ 0.001) and creatine kinase-2 (p ≤ 0.001) in both IS and IR subjects. Furthermore, physical activity was positively associated with levels of creatinine (p ≤ 0.01) and total vitamin D (p = 0.006) in the IR group and AST (p = 0.001), folate (p = 0.001), and hematocrit (p = 0.007) in the IS group. Conversely, physical inactivity was negatively associated with the white blood cell count (p = 0.001) and an absolute number of lymphocytes (p = 0.003) in the IR subjects and with triglycerides (p = 0.005) and GGT-2 (p ≤ 0.001) in the IS counterparts. (4) Conclusions: An independent effect of moderate physical activity was observed in non-obese apparently healthy individuals a with different HOMA-IR index. The effect was marked by an improved health profile including higher vitamin D and lower inflammatory markers in IRA compared to IRS, and a higher oxygen carrying capacity and lipid profile in ISA compared to the ISS counterparts.
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Affiliation(s)
- Shamma AlMuraikhy
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9712 CP Groningen, The Netherlands
| | - Najeha Anwardeen
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Aisha Naeem
- Ministry of Public Health, Doha P.O. Box 42, Qatar
- Department of Oncology and Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Rd., NW, Washington, DC 20007, USA
| | - Maha Sellami
- Physical Education Department (PE), College of Education, Qatar University, Doha P.O. Box 2713, Qatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9712 CP Groningen, The Netherlands
| | - Abdelali Agouni
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Mohamed A. Elrayess
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity. Int J Mol Sci 2022; 23:ijms231911142. [PMID: 36232443 PMCID: PMC9569927 DOI: 10.3390/ijms231911142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/08/2022] [Accepted: 09/16/2022] [Indexed: 12/02/2022] Open
Abstract
Impaired adipogenesis is associated with the development of insulin resistance and an increased risk of type 2 diabetes (T2D). GATA Binding Protein 3 (GATA3) is implicated in impaired adipogenesis and the onset of insulin resistance. Therefore, we hypothesize that inhibition of GATA3 could promote adipogenesis, restore healthy fat distribution, and enhance insulin signaling. Primary human preadipocytes were treated with GATA3 inhibitor (DNAzyme hgd40). Cell proliferation, adipogenic capacity, gene expression, and insulin signaling were measured following well-established protocols. BALB/c mice were treated with DNAzyme hgd40 over a period of 2 weeks. Liposomes loaded with DNAzyme hgd40, pioglitazone (positive), or vehicle (negative) controls were administered subcutaneously every 2 days at the right thigh. At the end of the study, adipose tissues were collected and weighed from the site of injection, the opposite side, and the omental depot. Antioxidant enzyme (superoxide dismutase and catalase) activities were assessed in animals’ sera, and gene expression was measured using well-established protocols. In vitro GATA3 inhibition induced the adipogenesis of primary human preadipocytes and enhanced insulin signaling through the reduced expression of p70S6K. In vivo GATA3 inhibition promoted adipogenesis at the site of injection and reduced MCP-1 expression. GATA3 inhibition also reduced omental tissue size and PPARγ expression. These findings suggest that modulating GATA3 expression offers a potential therapeutic benefit by correcting impaired adipogenesis, promoting healthy fat distribution, improving insulin sensitivity, and potentially lowering the risk of T2D.
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Shen FC, Chen ME, Wu WT, Kuo IC, Niu SW, Lee JJ, Hung CC, Chang JM, Hwang SJ. Normal weight and waist obesity indicated by increased total body fat associated with all-cause mortality in stage 3–5 chronic kidney disease. Front Nutr 2022; 9:982519. [PMID: 36185692 PMCID: PMC9523665 DOI: 10.3389/fnut.2022.982519] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/25/2022] [Indexed: 11/13/2022] Open
Abstract
Patients with chronic kidney disease (CKD) demonstrate a survival benefit with a high body mass index (BMI); this is the obesity paradox. Central obesity has a higher prognostic value than BMI, even in those with normal weight. Whether total body fat percentage (TBF%) provides more information than BMI and waist circumference (WC) remains unknown. We included 3,262 Asian patients with stage 3–5 CKD and divided these patients by TBF% and waist-to-height ratio (WHtR) quartiles (Q1–Q4). TBF% was associated with BMI, WC, nutritional markers, and C-reactive protein. In all patients, BMI but not TBF% or WHtR demonstrated a survival paradox. In patients with BMI <25 kg/m2, but not in those with BMI ≥ 25 kg/m2, TBF% Q4 and WHtR Q4 were associated with all-cause mortality, with hazard ratios [HRs; 95% confidence intervals (CIs)] of 2.35 (1.31–4.22) and 1.38 (1.06–1.80), respectively. The HRs of TBF% Q4 for all-cause mortality were 2.90 (1.50–5.58) in patients with a normal WC and 3.81 (1.93–7.50) in patients with normal weight and normal WC (All P for interaction < 0.05). In conclusion, TBF% can predict all-cause mortality in patients with advanced CKD and a normal weight, normal WC, or both.
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Affiliation(s)
- Feng-Ching Shen
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mei-En Chen
- Department of Nutrition and Dietetics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wei-Tsung Wu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - I-Ching Kuo
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sheng-Wen Niu
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Jung Lee
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Chih Hung
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- *Correspondence: Chi-Chih Hung
| | - Jer-Ming Chang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shang-Jyh Hwang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Zhang F, Han Y, Wang H, Li Y, Yan Z. Diagnostic test accuracy of waist-to-height ratio as a screening tool for cardiovascular risk in children and adolescents: a meta-analysis. Ann Hum Biol 2022; 49:217-227. [PMID: 36121693 DOI: 10.1080/03014460.2022.2126523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
CONTEXT Waist-to-height ratio (WHtR) is a controversial evaluation index of cardiovascular risk factors (CVRFs) in children and adolescents. OBJECTIVE To assess the accuracy of WHtR as a measure to screen for clusters of at least one CVRF (CVRF1), two CVRFs (CVRF2), and three CVRFs (CVRF3) in different ages, sexes, regions and cut-offs. METHODS The PubMed, Web of Science, EBSCOhost, Springer, Taylor & Francis Online, Wiley Online Library, Wanfang, and CNKI databases were searched for eligible publications up to June 2021. The QUADAS-2 checklist was used to assess the methodology of the included studies. RESULTS Twenty-two studies that evaluated 85281 children and adolescents aged 5-19 years were included in the meta-analysis. The AUSROC values were 0.56 (95% CI: 0.54-0.57), 0.82 (95% CI: 0.81-0.83), and 0.89 (95% CI: 0.89-0.90) for CVRF1, CVRF2, and CVRF3, respectively. Higher AUSROC values were found for adolescents (12-19 years), that is, 0.91 (95% CI: 0.88-0.93), 0.90 (95% CI: 0.87-0.92) for males, and 0.91 (95% CI: 0.90-0.91) for a cut-off of ≥ 0.51 in the identification of CVRF3. CONCLUSION WHtR can be used as an accurate screening tool for CVRF3 and CVRF2 in children and adolescents, and it is recommended to select different cut-offs according to different ages, sexes, and regions.
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Affiliation(s)
- Fusheng Zhang
- College of Physical Education and Health, Guangxi Normal University, Guilin, China.,School of Physical Education, Zhaotong University, Zhaotong, China
| | - Yanbai Han
- College of Physical Education and Health, Guangxi Normal University, Guilin, China
| | - Hongli Wang
- College of Physical Education and Health, Guangxi Normal University, Guilin, China
| | - Yong Li
- College of Physical Education and Health, Guangxi Normal University, Guilin, China
| | - Zhiwei Yan
- Department of Sports Rehabilitation, College of Human Kinesiology, Shenyang Sport University, Shenyang, China
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Chen YC, Li WC, Ke PH, Chen IC, Yu W, Huang HY, Xiong XJ, Chen JY. Association between metabolic body composition status and vitamin D deficiency: A cross-sectional study. Front Nutr 2022; 9:940183. [PMID: 35967768 PMCID: PMC9365955 DOI: 10.3389/fnut.2022.940183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/08/2022] [Indexed: 11/13/2022] Open
Abstract
This study aimed to investigate the risk of vitamin D deficiency in a relatively healthy Asian population, with (i) metabolically healthy normal weight (MHNW) (homeostasis model assessment-insulin resistance [HOMA-IR] < 2. 5 without metabolic syndrome [MS], body mass index [BMI] < 25), (ii) metabolically healthy obesity (MHO) (HOMA-IR < 2.5, without MS, BMI ≥ 25), (iii) metabolically unhealthy normal weight (MUNW) (HOMA-IR ≥ 2.5, or with MS, BMI < 25), and (iv) metabolically unhealthy obesity (MUO) (HOMA-IR ≥ 2.5, or with MS, BMI ≥ 25) stratified by age and sex. This cross-sectional study involved 6,655 participants aged ≥ 18 years who underwent health checkups between 2013 and 2016 at the Chang Gung Memorial Hospital. Cardiometabolic and inflammatory markers including anthropometric variables, glycemic indices, lipid profiles, high-sensitivity C-reactive protein (hs-CRP), and serum 25-hydroxy vitamin D levels, were retrospectively investigated. Compared to the MHNW group, the MHO group showed a higher odds ratio (OR) [1.35, 95% confidence interval (CI) 1.05-1.73] for vitamin D deficiency in men aged < 50 years. By contrast, in men aged > 50 years, the risk of vitamin D deficiency was higher in the MUO group (OR 1.44, 95% CI 1.05-1.97). Among women aged < and ≥ 50 years, the MUO group demonstrated the highest risk for vitamin D deficiency, OR 2.33 vs. 1.54, respectively. Our study revealed that in women of all ages and men aged > 50 years, MUO is associated with vitamin D deficiency and elevated levels of metabolic biomarkers. Among men aged < 50 years, MHO had the highest OR for vitamin D deficiency.
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Affiliation(s)
- Yi-Chuan Chen
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Wen-Cheng Li
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,College of Medicine, Chang-Gung University, Taoyuan, Taiwan.,Department of Health Management, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, China
| | - Pin-Hsuan Ke
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - I-Chun Chen
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Wei Yu
- Department of Health Management, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, China
| | - Hsiung-Ying Huang
- Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, China
| | - Xue-Jie Xiong
- Department of Oncology, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, China
| | - Jau-Yuan Chen
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,College of Medicine, Chang-Gung University, Taoyuan, Taiwan
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Reynés B, Cifre M, Palou A, Oliver P. Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats. Nutrients 2022; 14:nu14112277. [PMID: 35684076 PMCID: PMC9183119 DOI: 10.3390/nu14112277] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 11/16/2022] Open
Abstract
Perinatal nutrition has a well-known influence on obesity susceptibility. We previously demonstrated the protective anti-obesity effects of perinatal leptin administration. Celastrol is a natural compound acting as a leptin sensitizer with anti-obesity effects when administered in adult animals. Here, we aimed to determine if perinatal treatment with leptin, celastrol, or their combination was able to improve metabolic health in animals fed an isocaloric high-fat (HF) diet. Leptin and/or celastrol or their vehicle were administered orally to rats during the suckling period. After weaning, animals were chronically pair-fed with an HF diet provided isocaloric to the intake of a normal-fat diet by control animals to avoid obesity. Isocaloric HF feeding in vehicle-treated animals resulted in metabolic features characteristic of the metabolically obese, normal-weight (MONW) phenotype, i.e., obesity-related disturbances without increased body weight. Leptin treatment prevented liver fat deposition and insulin resistance, induced greater insulin and leptin signaling capacity, decreased gene expression of orexigenic signals at the hypothalamic level, and induced browning in retroperitoneal adipose tissue. However, celastrol treatment did not provide any protective effect and resulted in greater size of the retroperitoneal adipose depot, higher circulating glucose and insulin levels, and decreased leptin sensitivity capacity in adipose tissue. The co-administration of leptin ameliorated the negative effects of celastrol on the retroperitoneal depot, inducing browning and decreasing its size. In conclusion, the perinatal administration of leptin, but not celastrol, provided protection against the consequences of dietary unbalances leading to an MONW phenotype in adulthood.
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Affiliation(s)
- Bàrbara Reynés
- Nutrigenomics, Biomarkers and Risk Evaluation Group, University of the Balearic Islands, 07122 Palma, Spain; (B.R.); (M.C.); (P.O.)
- Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain
| | - Margalida Cifre
- Nutrigenomics, Biomarkers and Risk Evaluation Group, University of the Balearic Islands, 07122 Palma, Spain; (B.R.); (M.C.); (P.O.)
- CIBER of Pathophysiology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Andreu Palou
- Nutrigenomics, Biomarkers and Risk Evaluation Group, University of the Balearic Islands, 07122 Palma, Spain; (B.R.); (M.C.); (P.O.)
- Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain
- CIBER of Pathophysiology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: ; Tel.: +34-971-173-170
| | - Paula Oliver
- Nutrigenomics, Biomarkers and Risk Evaluation Group, University of the Balearic Islands, 07122 Palma, Spain; (B.R.); (M.C.); (P.O.)
- Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain
- CIBER of Pathophysiology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
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De Fano M, Bartolini D, Tortoioli C, Vermigli C, Malara M, Galli F, Murdolo G. Adipose Tissue Plasticity in Response to Pathophysiological Cues: A Connecting Link between Obesity and Its Associated Comorbidities. Int J Mol Sci 2022; 23:ijms23105511. [PMID: 35628322 PMCID: PMC9141504 DOI: 10.3390/ijms23105511] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/10/2022] [Accepted: 05/13/2022] [Indexed: 12/10/2022] Open
Abstract
Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiotropism and high remodeling capacity. Although the expansion of fat mass, by definition, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardiovascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells, low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orchestrated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new adipocytes appears to be the main instigator of the adipose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an altered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This “adipocentric view” extends the previous “expandability hypothesis”, which implies a reduced plasticity of the adipose organ at the nexus between unhealthy fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation, inflammation and cellular senescence as a novel triad orchestrating the conspiracy to adipose dysfunction. Finally, we discuss the scientific rationale for proposing adipose organ plasticity as a target to curb/prevent adiposity-linked cardio-metabolic complications.
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Affiliation(s)
- Michelatonio De Fano
- Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy; (M.D.F.); (C.T.); (C.V.); (M.M.)
| | - Desirèe Bartolini
- Department of Pharmaceutical Sciences, Human Anatomy Laboratory, University of Perugia, 06132 Perugia, Italy; (D.B.); (F.G.)
| | - Cristina Tortoioli
- Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy; (M.D.F.); (C.T.); (C.V.); (M.M.)
| | - Cristiana Vermigli
- Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy; (M.D.F.); (C.T.); (C.V.); (M.M.)
| | - Massimo Malara
- Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy; (M.D.F.); (C.T.); (C.V.); (M.M.)
| | - Francesco Galli
- Department of Pharmaceutical Sciences, Human Anatomy Laboratory, University of Perugia, 06132 Perugia, Italy; (D.B.); (F.G.)
| | - Giuseppe Murdolo
- Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy; (M.D.F.); (C.T.); (C.V.); (M.M.)
- Correspondence: ; Tel.: +39-(0)75-578-3301; Fax: +39-75-573-0855
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Vipin VA, Blesson CS, Yallampalli C. Maternal low protein diet and fetal programming of lean type 2 diabetes. World J Diabetes 2022; 13:185-202. [PMID: 35432755 PMCID: PMC8984567 DOI: 10.4239/wjd.v13.i3.185] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/30/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood. Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy, and impaired nutrition has been an immense issue across the globe. In recent years, type 2 diabetes (T2D) has reached epidemic proportion and is a severe public health problem in many countries. Although plenty of research has already been conducted to tackle T2D which is associated with obesity, little is known regarding the etiology and pathophysiology of lean T2D, a variant of T2D. Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D, although other mechanisms might also contribute to the pathology. Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype. In addition, clear sex-specific disease prevalence was observed in different studies. Consequently, more research is essential for the understanding of the etiology and pathophysiology of lean T2D, which might help to develop better disease prevention and treatment strategies. This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.
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Affiliation(s)
- Vidyadharan Alukkal Vipin
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States
| | - Chellakkan Selvanesan Blesson
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States
- Family Fertility Center, Texas Children's Hospital, Houston, TX 77030, United States
| | - Chandra Yallampalli
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States
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43
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Pujia R, Tarsitano MG, Arturi F, De Lorenzo A, Lenzi A, Pujia A, Montalcini T. Advances in Phenotyping Obesity and in Its Dietary and Pharmacological Treatment: A Narrative Review. Front Nutr 2022; 9:804719. [PMID: 35242796 PMCID: PMC8885626 DOI: 10.3389/fnut.2022.804719] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/21/2022] [Indexed: 12/20/2022] Open
Abstract
In recent times, it has become evident that there are individuals who, from a metabolic point of view, are affected by obesity but have a normal body mass index. There are also metabolically healthy individuals with a high body mass index who are thus are considered as to be affected by obesity obese. Understanding that individuals with obesity are phenotypically heterogeneous is a relatively novel concept which, although present in the scientific literature, unfortunately has not yet had an impact in clinical practice. However, common dietary approaches are not effective in treating large numbers of obese patients with obesity. This narrative review, based on the material searched via PubMed and the Web of Science up to October 2021, proposes a downsizing of the role of the body mass index in identifying the individual with "true obesity" since it is only partially useful, and suggests a new approach which also integrates the body composition and assessment of metabolic parameters. This approach leads to personalized therapies that work best for each obesity phenotype in reducing the risk of non-communicable diseases.
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Affiliation(s)
- Roberta Pujia
- Department of Medical and Surgical Science Nutrition Unit, University Magna Grecia, Catanzaro, Italy
| | - Maria Grazia Tarsitano
- Department of Medical and Surgical Science Nutrition Unit, University Magna Grecia, Catanzaro, Italy
| | - Franco Arturi
- Department of Medical and Surgical Science Nutrition Unit, University Magna Grecia, Catanzaro, Italy
| | - Antonino De Lorenzo
- Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy
| | - Andrea Lenzi
- Department of Experimental Medicine, University La Sapienza, Rome, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Science Nutrition Unit, University Magna Grecia, Catanzaro, Italy
| | - Tiziana Montalcini
- Department of Clinical and Experimental Medicine, Nutrition Unit, University Magna Grecia, Catanzaro, Italy
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Metabolic Obesity in People with Normal Body Weight (MONW)-Review of Diagnostic Criteria. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19020624. [PMID: 35055447 PMCID: PMC8776153 DOI: 10.3390/ijerph19020624] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/26/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022]
Abstract
Disorders of metabolic obesity with normal body weight (MONW) are widely recognized risk factors for the development of cardiovascular diseases and type 2 diabetes. Despite this, MONW is not diagnosed in clinical practice. There is no consensus on the definition of MONW, and measuring the degree of insulin resistance or obesity among apparently healthy, non-obese patients is not widely applicable. The awareness of the relationship between metabolic disorders such as MONW and a higher risk of mortality from cardiovascular causes and other related diseases prompts the need for action to be taken aimed at creating appropriate diagnostic models that will allow for the effective detection of those with metabolic abnormalities among people with normal body weight. Such actions are decisive in the prevention and treatment of diseases. Therefore, the purpose of this article is to review the MONW diagnostic criteria used over the years.
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Jose N, P K V, Kulirankal KG. Study of Endothelial Dysfunction in Patients With Non-alcoholic Fatty Liver Disease. Cureus 2021; 13:e20515. [PMID: 34950560 PMCID: PMC8687804 DOI: 10.7759/cureus.20515] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2021] [Indexed: 11/20/2022] Open
Abstract
Background Metabolic syndrome (syndrome X) is the name for a group of risk factors that raises your risk for heart disease and other health problems, such as diabetes and stroke. Dilatation of blood vessels following stress is a function of vasodilators produced by the endothelium. Flow-mediated vasodilation assesses endothelial function. In the case of endothelial dysfunction, flow-mediated vasodilation is impaired, resulting in decreased or even absence of vasodilation following stress. The easy availability of ultrasound machines nowadays and the non-invasive nature of the test make this a practical test for assessing endothelial dysfunction and the risk of cardiovascular diseases. Various studies have confirmed the presence of impaired flow-mediated vasodilation in patients with coronary artery disease. However, the presence of impaired flow-mediated vasodilation in individuals with risk factors but no cardiovascular diseases can prove that this can be used to predict individuals at risk. This study tries to confirm the presence of endothelial dysfunction in patients with non-alcoholic fatty liver disease (NAFLD) attending a tertiary center hospital in Kochi. Objectives The study's main aim is to compare flow-mediated dilatation in patients with NAFLD and normal individuals. Materials and methods The comparative study was conducted among 50 patients attending various outpatient departments in Amrita Institute of Medical Sciences, Kochi. History and examination of cases and controls and relevant investigations were done after obtaining consent. In addition, both groups underwent measurement of flow-mediated vasodilation in the radiology department. Data were entered in Microsoft Excel and were analyzed using SPSS. Results Flow-mediated vasodilation was found to be less in patients with fatty liver (7.37 ± 2.75) when compared to individuals with normal liver (12.41 ± 3.71). In addition, flow-mediated vasodilatation was inversely proportional to BMI and age. Conclusion This study has proved that there will be endothelial dysfunction in NAFLD, as shown by the decrease in flow-mediated vasodilation when compared with normal liver.
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Affiliation(s)
- Nijin Jose
- Internal Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, IND
| | - Vasant P K
- Internal Medicine, Amrita Institute of Medical Sciences, Kochi, IND
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Ezemaduka Okoli CB, Woldu HG, Peterson CA. Low Urinary Iodine Concentration Is Associated with Increased Risk for Elevated Plasma Glucose in Females: An Analysis of NHANES 2011-12. Nutrients 2021; 13:4523. [PMID: 34960073 PMCID: PMC8708116 DOI: 10.3390/nu13124523] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/13/2021] [Accepted: 12/15/2021] [Indexed: 12/17/2022] Open
Abstract
Iodine intake in the US has declined in recent years. Iodine insufficiency increases the risk for inadequate thyroid hormone production and there is growing evidence that sub-clinical hypothyroidism may be disruptive to metabolic health, including insulin resistance (IR). We investigated the association between urinary iodine concentrations (UIC), a measurement of iodine status, and IR in adults. Data from 1286 US adults (≥20 years) in the NHANES 2011-2012 were analyzed. Two subgroups (low = UIC < 100 µg/L and normal = UIC ≥ 100 µg/L) were compared for markers of IR, including fasting plasma glucose (FPG) and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1C). Chi-square test, both linear and logistic regression models were used. In males, there were no significant associations between UIC and markers of IR; however, females with normal UIC had greater risks for elevated HOMA-IR (AOR = 0.56, 95% CI= 0.32-0.99) and HbA1C (AOR = 0.56, 95% CI = 0.34-0.90), while females with low UIC had a greater risk for FPG ≥ 5.6 mmol/L (AOR = 1.73, 95% CI = 1.09-2.72). Results only partially support our hypothesis that UIC is associated with the odds of IR in adults. The finding of an increased risk for elevated FPG, a marker of prediabetes, in female adults with low iodine status requires further investigation.
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Affiliation(s)
| | - Henok G. Woldu
- Department of Health Management and Informatics, School of Medicine, University of Missouri, Columbia, MO 65211, USA;
| | - Catherine A. Peterson
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
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Gallegos-Cabriales EC, Rodriguez-Ayala E, Laviada-Molina HA, Nava-Gonzalez EJ, Salinas-Osornio RA, Orozco L, Leal-Berumen I, Castillo-Pineda JC, Gonzalez-Lopez L, Escudero-Lourdes C, Cornejo-Barrera J, Escalante-Araiza F, Huerta-Avila EE, Buenfil-Rello FA, Peschard VG, Silva E, Veloz-Garza RA, Martinez-Hernandez A, Barajas-Olmos FM, Molina-Segui F, Gonzalez-Ramirez L, Arjona-Villicaña RD, Hernandez-Escalante VM, Gaytan-Saucedo JF, Vaquera Z, Acebo-Martinez M, Murillo-Ramirez A, Diaz-Tena SP, Figueroa-Nuñez B, Valencia-Rendon ME, Garzon-Zamora R, Viveros-Paredes JM, Valdovinos-Chavez SB, Comuzzie AG, Haack K, Thorsell AA, Han X, Cole SA, Bastarrachea RA. Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults. BIOLOGY 2021; 10:1342. [PMID: 34943258 PMCID: PMC8698545 DOI: 10.3390/biology10121342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/11/2021] [Accepted: 12/12/2021] [Indexed: 11/16/2022]
Abstract
We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.
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Affiliation(s)
- Esther C. Gallegos-Cabriales
- Facultad de Enfermería, Universidad Autónoma de Nuevo León (UANL), Monterrey 64460, Mexico; (E.C.G.-C.); (R.A.V.-G.); (S.B.V.-C.)
| | - Ernesto Rodriguez-Ayala
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
| | - Hugo A. Laviada-Molina
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | | | - Rocío A. Salinas-Osornio
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Lorena Orozco
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Irene Leal-Berumen
- Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, Chihuahua 31125, Mexico;
| | - Juan Carlos Castillo-Pineda
- Departamento de Nutrición Humana, Universidad Latina de América, Morelia 58170, Mexico; (J.C.C.-P.); (A.M.-R.); (S.P.D.-T.)
| | - Laura Gonzalez-Lopez
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Claudia Escudero-Lourdes
- Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosi 78240, Mexico; (C.E.-L.); (M.A.-M.)
| | - Judith Cornejo-Barrera
- Departamento de Enseñanza, Postgrado e Investigación, Hospital Infantil de Tamaulipas, Ciudad Victoria 87150, Mexico;
| | - Fabiola Escalante-Araiza
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Eira E. Huerta-Avila
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Fatima A. Buenfil-Rello
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Vanessa-Giselle Peschard
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
| | - Eliud Silva
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, Lomas Anahuac 52786, Mexico; (E.R.-A.); (F.E.-A.); (V.-G.P.); (E.S.)
| | - Rosa A. Veloz-Garza
- Facultad de Enfermería, Universidad Autónoma de Nuevo León (UANL), Monterrey 64460, Mexico; (E.C.G.-C.); (R.A.V.-G.); (S.B.V.-C.)
| | - Angelica Martinez-Hernandez
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Francisco M. Barajas-Olmos
- Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, SS, Ciudad de México 14610, Mexico; (L.O.); (E.E.H.-A.); (A.M.-H.); (F.M.B.-O.)
| | - Fernanda Molina-Segui
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Lucia Gonzalez-Ramirez
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Ruy D. Arjona-Villicaña
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Victor M. Hernandez-Escalante
- Escuela de Ciencias de la Salud, Universidad Marista de Mérida, Mérida 97300, Mexico; (H.A.L.-M.); (F.M.-S.); (L.G.-R.); (R.D.A.-V.); (V.M.H.-E.)
| | - Janeth F. Gaytan-Saucedo
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Zoila Vaquera
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Monica Acebo-Martinez
- Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosi 78240, Mexico; (C.E.-L.); (M.A.-M.)
| | - Areli Murillo-Ramirez
- Departamento de Nutrición Humana, Universidad Latina de América, Morelia 58170, Mexico; (J.C.C.-P.); (A.M.-R.); (S.P.D.-T.)
| | - Sara P. Diaz-Tena
- Departamento de Nutrición Humana, Universidad Latina de América, Morelia 58170, Mexico; (J.C.C.-P.); (A.M.-R.); (S.P.D.-T.)
| | - Benigno Figueroa-Nuñez
- Clínica de Enfermedades Crónicas y Procedimientos Especiales (CECYPE), Morelia 58249, Mexico;
| | - Melesio E. Valencia-Rendon
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Rafael Garzon-Zamora
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Juan Manuel Viveros-Paredes
- Departamento de Nutrición, Universidad del Valle de Atemajac (UNIVA), Zapopan 45050, Mexico; (R.A.S.-O.); (L.G.-L.); (M.E.V.-R.); (R.G.-Z.); (J.M.V.-P.)
| | - Salvador B. Valdovinos-Chavez
- Facultad de Enfermería, Universidad Autónoma de Nuevo León (UANL), Monterrey 64460, Mexico; (E.C.G.-C.); (R.A.V.-G.); (S.B.V.-C.)
| | | | - Karin Haack
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | | | - Xianlin Han
- Department of Medicine, Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA;
| | - Shelley A. Cole
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
| | - Raul A. Bastarrachea
- Population Health Program, Southwest National Primate Research Center (SNPRC), Texas Biomedical Research Institute, San Antonio, TX 78227-0549, USA; (F.A.B.-R.); (J.F.G.-S.); (Z.V.); (K.H.); (S.A.C.)
- Sansum Diabetes Research Institute, Santa Barbara, CA 93105, USA;
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Khalil M, Hayek S, Khalil N, Serale N, Vergani L, Calasso M, De Angelis M, Portincasa P. Role of Sumac (Rhus coriaria L.) in the management of metabolic syndrome and related disorders: Focus on NAFLD-atherosclerosis interplay. J Funct Foods 2021; 87:104811. [DOI: 10.1016/j.jff.2021.104811] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Lee G, Choi S, Park SM. Association of waist circumference with muscle and fat mass in adults with a normal body mass index. Nutr Res Pract 2021; 15:604-612. [PMID: 34603608 PMCID: PMC8446684 DOI: 10.4162/nrp.2021.15.5.604] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 09/21/2020] [Accepted: 10/26/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/OBJECTIVES We aimed to investigate the association of waist circumference (WC) with body composition among individuals with a normal body mass index (BMI) to distinguish muscle and fat mass, as both affect health differently. SUBJECTS/METHODS We analyzed dual-energy X-ray absorptiometry data (derived from the Korean National Health and Nutrition Survey, which includes information on fat and lean mass) of 7,493 adults with a normal BMI. Subjects were categorized into four groups of increasing WC. The fourth group was defined as being centrally obese. Each number of subjects are as follows: 1,870, 695, 231, and 39 among men and 3,054, 1,100, 406, and 98 among women. We conducted a sex-stratified linear regression analysis of body composition according to WC group after adjustments for covariates. RESULTS We observed a positive association of body fat with increasing WC in both men and women (all P for trend: < 0.001). The adjusted mean values for percent body fat with 95% confidence intervals (CIs) according to the four WC groups in ascending order were 17.8 (17.5–18.3), 21.0 (20.6–21.5), 22.1 (21.5–22.8), and 25.1 (24.2–26.1) in men and 29.7 (29.4–30.0), 32.0 (31.6–32.3), 32.9 (32.4–33.4), and 34.7 (33.2–36.1) in women. However, there was an inverted J-shaped association between muscle mass and WC. The fourth group had a higher percent body fat and lower muscle mass than other groups. The adjusted mean values for appendicular skeletal muscle mass index (kg/m2) with 95% CIs according to the four WC groups in ascending order were 7.55 (7.51–7.59), 7.62 (7.56–7.68), 7.65 (7.56–7.74), and 7.22 (7.04–7.41) in men and 5.83 (5.80–5.85), 5.96 (5.92–6.00), 6.03 (5.96–6.10), and 5.88 (5.73–6.03). CONCLUSIONS There was a positive association between body fat and WC among individuals with normal BMI; conversely there was an inverted J-shaped association between lean body mass and WC. Our findings support the WC measurement should be included in obesity evaluations for adults with a normal BMI.
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Affiliation(s)
- Gyeongsil Lee
- Department of Family Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Seulggie Choi
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
| | - Sang Min Park
- Department of Family Medicine, Seoul National University Hospital, Seoul 03080, Korea.,Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
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Okubo S, Shindoh J, Kobayashi Y, Umino R, Akabane M, Kojima K, Hashimoto M. Adipose Tissue Distribution Predicts Prognosis of Cirrhotic Patients Undergoing Hepatectomy for Hepatocellular Carcinoma. Ann Surg Oncol 2021; 28:6738-6746. [PMID: 33554286 DOI: 10.1245/s10434-021-09658-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/09/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Body composition data are reportedly correlated with patient prognosis for various cancers. However, little is known about the prognostic impact of adipose tissue distribution among patients with hepatocellular carcinoma (HCC). METHODS Data for 181 consecutive cirrhotic patients who underwent hepatectomy for HCC were retrospectively reviewed. The clinical significance of the visceral-to-subcutaneous adipose tissue ratio (VSR) was investigated through analysis of short- and long-term surgical outcomes. RESULTS Of the 181 patients, 60 (33%) were classified as the high-VSR group and 121 (67%) as the low-VSR group. Although VSR was not correlated with a risk of postoperative morbidity, multivariate analysis confirmed that a higher VSR was significantly correlated with a shorter time to interventional failure (hazard ratio [HR] 2.24; P = 0.008) and overall survival (HR 2.65; P = 0.001) independently of American Joint Committed on Cancer stage or preoperative nutritional status. Analysis of the recurrence patterns showed that the proportion of unresectable recurrence at the initial recurrence event was significantly higher in the high-VSR group (39% vs. 18%; P = 0.025). The yearly transition probabilities, defined by a Markov model from postoperative R0 status to advanced disease or death (7.6% vs. 1.5%, P < 0.001) and early recurrence stage to advanced disease or death (15.4% vs. 2.8%, P = 0.004), were higher in the high-VSR group, suggesting that patients with a higher VSR are vulnerable to disease progression. CONCLUSION A high VSR was found to be an independent predictor of disease progression and poor prognosis for HCC patients with underlying liver cirrhosis having resection for HCC.
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Affiliation(s)
- Satoshi Okubo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Yuta Kobayashi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Ryosuke Umino
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Miho Akabane
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Kazutaka Kojima
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Masaji Hashimoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
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