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Corrao S, Calvo L, Granà W, Scibetta S, Mirarchi L, Amodeo S, Falcone F, Argano C. Metabolic dysfunction-associated steatotic liver disease: A pathophysiology and clinical framework to face the present and the future. Nutr Metab Cardiovasc Dis 2025; 35:103702. [PMID: 39358105 DOI: 10.1016/j.numecd.2024.07.019] [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: 05/10/2024] [Revised: 07/16/2024] [Accepted: 07/29/2024] [Indexed: 10/04/2024]
Abstract
AIMS This review aims to provide a straightforward conceptual framework for the knowledge and understanding of Metabolic dysfunction-associated steatotic liver disease (MASLD) in the broad spectrum of steatotic liver disease and to point out the need to consider metabolic dysfunction and comorbidities as interrelated factors for a holistic approach to fatty liver disease. DATA SYNTHESIS MASLD is the new proposed term for steatotic liver disease that replaces the old terminology of non-alcoholic fatty liver disease. This term focused on the relationship between metabolic alteration and hepatic steatosis, reflecting a growing comprehension of the association between metabolic dysfunction and hepatic steatosis. Numerous factors and conditions contribute to the underlying mechanisms, including central obesity, insulin resistance, adiponectin, lipid metabolism, liver function, dietary influences, the composition of intestinal microbiota, and genetic factors. The development of the condition, however, involves a more intricate network of components, such as neurotensin and Advanced Glycation End Products, highlighting the complexity of its pathogenesis. CONCLUSIONS MASLD must be regarded as a complex clinical problem in which only a holistic approach can win through the coordination of multi-professional and multi-speciality interventions.
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Affiliation(s)
- Salvatore Corrao
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy; Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties [PROMISE], University of Palermo, Italy.
| | - Luigi Calvo
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Walter Granà
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Salvatore Scibetta
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Luigi Mirarchi
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Simona Amodeo
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Fabio Falcone
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy; Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties [PROMISE], University of Palermo, Italy
| | - Christiano Argano
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
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Susca N, Leone P, Prete M, Cozzio S, Racanelli V. Adipose failure through adipocyte overload and autoimmunity. Autoimmun Rev 2024; 23:103502. [PMID: 38101692 DOI: 10.1016/j.autrev.2023.103502] [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: 11/21/2023] [Accepted: 12/10/2023] [Indexed: 12/17/2023]
Abstract
Metabolic syndrome poses a great worldwide threat to the health of the patients. Increased visceral adiposity is recognized as the main determinant of the detrimental clinical effects of insulin resistance. Inflammation and immune system activation in the adipose tissue (AT) have a central role in the pathophysiology of metabolic syndrome, but the mechanisms linking increased adiposity to immunity in the AT remain in part elusive. In this review, we support the central role of adipocyte overload and relative adipose failure as key determinants in triggering immune aggression to AT. This provides a mechanistic explanation of the relative metabolic wellness of metabolically normal obese people and the disruption in insulin signaling in metabolically obese lean people.
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Affiliation(s)
- Nicola Susca
- Department of Interdisciplinary Medicine, School of Medicine, 'Aldo Moro' University of Bari, 70124 Bari, Italy
| | - Patrizia Leone
- Department of Interdisciplinary Medicine, School of Medicine, 'Aldo Moro' University of Bari, 70124 Bari, Italy
| | - Marcella Prete
- Department of Interdisciplinary Medicine, School of Medicine, 'Aldo Moro' University of Bari, 70124 Bari, Italy
| | - Susanna Cozzio
- U.O. di Medicina Interna, Ospedale di Rovereto, Azienda Sanitaria per i Servizi Provinciali di Trento, Trento, Italy
| | - Vito Racanelli
- Centre for Medical Sciences - CISMed, University of Trento and Department of Internal Medicine, Santa Chiara Hospital, Trento, Italy.
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Trevellin E, Bettini S, Pilatone A, Vettor R, Milan G. Obesity, the Adipose Organ and Cancer in Humans: Association or Causation? Biomedicines 2023; 11:biomedicines11051319. [PMID: 37238992 DOI: 10.3390/biomedicines11051319] [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: 02/14/2023] [Revised: 04/18/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open
Abstract
Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause-effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to the immunometabolism and secretome. Moreover, AT and cancer share similar morpho-functional units which regulate tissue expansion: the adiponiche and tumour-niche, respectively. Through direct and indirect interactions involving different cellular types and molecular mechanisms, the obesity-altered adiponiche contributes to cancer development, progression, metastasis and chemoresistance. Moreover, modifications to the gut microbiome and circadian rhythm disruption also play important roles. Clinical studies clearly demonstrate that weight loss is associated with a decreased risk of developing obesity-related cancers, matching the reverse-causality criteria and providing a causality correlation between the two variables. Here, we provide an overview of the methodological, epidemiological and pathophysiological aspects, with a special focus on clinical implications for cancer risk and prognosis and potential therapeutic interventions.
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Affiliation(s)
- Elisabetta Trevellin
- Center for the Study and Integrated Treatment of Obesity (CeSTIO), Internal Medicine 3, Department of Medicine, University Hospital of Padova, 35128 Padova, Italy
| | - Silvia Bettini
- Center for the Study and Integrated Treatment of Obesity (CeSTIO), Internal Medicine 3, Department of Medicine, University Hospital of Padova, 35128 Padova, Italy
| | - Anna Pilatone
- Center for the Study and Integrated Treatment of Obesity (CeSTIO), Internal Medicine 3, Department of Medicine, University Hospital of Padova, 35128 Padova, Italy
| | - Roberto Vettor
- Center for the Study and Integrated Treatment of Obesity (CeSTIO), Internal Medicine 3, Department of Medicine, University Hospital of Padova, 35128 Padova, Italy
| | - Gabriella Milan
- Center for the Study and Integrated Treatment of Obesity (CeSTIO), Internal Medicine 3, Department of Medicine, University Hospital of Padova, 35128 Padova, Italy
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Stone M, Lukaczer D, D’Adamo CR, Dotson N, Volkov A, Minich D, Metti D, Leary M, Class M, Carullo M, Lundquist E, Eck B, Ordovas J, Lamb J, Bland J. LIFEHOUSE’s Functional Nutrition Examination (Physical Exam, Anthropometrics, and Selected Biomarkers) Informs Personalized Wellness Interventions. J Pers Med 2023; 13:jpm13040594. [PMID: 37108980 PMCID: PMC10145881 DOI: 10.3390/jpm13040594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 03/21/2023] [Accepted: 03/24/2023] [Indexed: 03/31/2023] Open
Abstract
Each individual has a unique and interacting set of genetic, lifestyle, and environmental factors that are reflected in their physical exam and laboratory biomarkers and significantly impact their experience of health. Patterns of nutrient deficiency signs and biomarker levels below health-promoting thresholds have been identified in national nutrition surveys. However, identifying these patterns remains a challenge in clinical medicine for many reasons, including clinician training and education, clinical time restraints, and the belief that these signs are both rare and recognizable only in cases of severe nutritional deficiencies. With an increased interest in prevention and limited resources for comprehensive diagnostic evaluations, a functional nutrition evaluation may augment patient-centered screening evaluations and personalized wellness programs. During LIFEHOUSE, we have documented physical exam, anthropometric, and biomarker findings that may increase the recognition of these wellness-challenging patterns in a population of 369 adult employees working in two occupational areas: administrative/sales and manufacturing/warehouse. Distinct and significant physical exam differences and constellations of biomarker abnormalities were identified. We present these patterns of physical exam findings, anthropometrics, and advanced biomarkers to assist clinicians in diagnostic and therapeutic interventions that may stem the loss of function that precedes the development of the non-communicable chronic diseases of aging.
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Bays HE, Bindlish S, Clayton TL. Obesity, diabetes mellitus, and cardiometabolic risk: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2023. OBESITY PILLARS 2023; 5:100056. [PMID: 37990743 PMCID: PMC10661981 DOI: 10.1016/j.obpill.2023.100056] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 01/25/2023] [Indexed: 11/23/2023]
Abstract
Background This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) is intended to provide clinicians an overview of type 2 diabetes mellitus (T2DM), an obesity-related cardiometabolic risk factor. Methods The scientific support for this CPS is based upon published citations and clinical perspectives of OMA authors. Results Topics include T2DM and obesity as cardiometabolic risk factors, definitions of obesity and adiposopathy, and mechanisms for how obesity causes insulin resistance and beta cell dysfunction. Adipose tissue is an active immune and endocrine organ, whose adiposopathic obesity-mediated dysfunction contributes to metabolic abnormalities often encountered in clinical practice, including hyperglycemia (e.g., pre-diabetes mellitus and T2DM). The determination as to whether adiposopathy ultimately leads to clinical metabolic disease depends on crosstalk interactions and biometabolic responses of non-adipose tissue organs such as liver, muscle, pancreas, kidney, and brain. Conclusions This review is intended to assist clinicians in the care of patients with the disease of obesity and T2DM. This CPS provides a simplified overview of how obesity may cause insulin resistance, pre-diabetes, and T2DM. It also provides an algorithmic approach towards treatment of a patient with obesity and T2DM, with "treat obesity first" as a priority. Finally, treatment of obesity and T2DM might best focus upon therapies that not only improve the weight of patients, but also improve the health outcomes of patients (e.g., cardiovascular disease and cancer).
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Affiliation(s)
- Harold Edward Bays
- Louisville Metabolic and Atherosclerosis Research Center, University of Louisville School of Medicine, 3288 Illinois Avenue, Louisville, KY, 40213, USA
| | - Shagun Bindlish
- Diabetology, One Medical, Adjunct Faculty Touro University, CA, USA
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Bigarella LG, Ballardin AC, Couto LS, de Ávila ACP, Ballotin VR, Ingracio AR, Martini MP. The Impact of Obesity on Plastic Surgery Outcomes: A Systematic Review and Meta-analysis. Aesthet Surg J 2022; 42:795-807. [PMID: 35037936 DOI: 10.1093/asj/sjab397] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Obesity is a potential risk factor for complications in plastic surgeries. However, the data presented by primary studies are contradictory. OBJECTIVES The aim of this study was to summarize and clarify the divergences in the literature to provide a better understanding of the impact of obesity in different plastic surgery procedures. METHODS We conducted a systematic review and meta-analysis of the impact of obesity on plastic surgery outcomes. Searches were conducted in MEDLINE, LILACS, SciELO, Scopus, Embase, Web of Science, Opengrey.eu, and the Cochrane Database of Systematic Reviews. The primary outcomes assessed were surgical complications, medical complications, and reoperation rates. The secondary outcome assessed was patient satisfaction. Subgroup analysis was performed to investigate the impact of each BMI category on the outcomes. RESULTS Ninety-three articles were included in the qualitative synthesis, and 91 were used in the meta-analysis. Obese participants were 1.62 times more likely to present any of the primary outcomes (95% CI, 1.48-1.77; P < 0.00001). The highest increase in risk among plastic surgery types was observed in cosmetic procedures (risk ratio [RR], 1.80; 95% CI, 1.43-2.32; P < 0.00001). Compared with normal-weight participants, overweight participants presented a significantly increased RR for complications (RR, 1.16; 95% CI, 1.07-1.27; P = 0.0004). Most authors found no relation between BMI and overall patient satisfaction. CONCLUSIONS Obesity leads to more complications and greater incidence of reoperation compared with nonobese patients undergoing plastic surgeries. However, this effect is not evident in reconstructive surgeries in areas of the body other than the breast.
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Affiliation(s)
| | | | - Luísa Serafini Couto
- School of Medicine, Universidade de Caxias do Sul (UCS) , Caxias do Sul , Brazil
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Thomas MC. The clustering of Cardiovascular, Renal, Adipo-Metabolic Eye and Liver disease with type 2 diabetes. Metabolism 2022; 128:154961. [PMID: 34958818 DOI: 10.1016/j.metabol.2021.154961] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 11/25/2021] [Accepted: 12/13/2021] [Indexed: 12/21/2022]
Abstract
Type 2 diabetes is associated with an increased risk of cardiovascular disease, heart failure, chronic kidney disease, fatty liver disease, eye and foot disease. But equally, these conditions are associated with an increased risk of type 2 diabetes. Rather than being simply considered complications of diabetes, as exists within a 'pure' type 1 diabetes paradigm, both type 2 diabetes and its comorbidities are primarily caused by a failure to efficiently sequester excess energy leading to the accumulation of sick fat (adiposopathy). Type 2 diabetes is a symptom of a chronic disease complex, just as cardiovascular, renal, eye, foot and/or liver disease, are. In addition, each of these conditions feed forward so that dysfunction in one system accelerates dysfunction in another, partly through their shared pathogenesis and partly due dysfunction that follows in their wake. This review will explore the sticky, brittle conglomeration of CArdiac, Renal, Adipo-Metabolic, Eye and Liver disease (hereafter collectively known as CARAMEL disease) that is coincident in most patients with type 2 diabetes and contextualise the recent changes in diabetes guidelines that now specifically focus on identifying and aggressively managing these high-risk individuals with it.
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Affiliation(s)
- M C Thomas
- Department of Diabetes, Monash University, Melbourne, Australia.
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Bays HE, Shrestha A, Niranjan V, Khanna M, Kambhamettu L. Obesity Pillars Roundtable: Obesity and South Asians. OBESITY PILLARS (ONLINE) 2022; 1:100006. [PMID: 37990701 PMCID: PMC10661885 DOI: 10.1016/j.obpill.2021.100006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/23/2021] [Accepted: 12/23/2021] [Indexed: 11/23/2023]
Abstract
Background Compared to other races/ethnicities, individuals from South Asia with obesity are strikingly susceptible to the presence of CVD risk factors and onset of CVD events - in part due to adiposopathic anatomic and metabolic responses to positive caloric balance. Pathogenic endocrine and immune effects of adipocyte hypertrophy and visceral fat accumulation both directly and indirectly promote among the most common metabolic diseases encountered in clinical practice - many being major cardiovascular disease (CVD) risk factors. This is especially applicable to those from South Asia - largely due to genetics, epigenetics, unhealthful nutrition, and physical inactivity. Methods This roundtable discussion included 4 obesity specialists engaged in the clinical management of obesity among patients of South Asian descent. Results Patients with obesity from South Asia have increased adipocyte size, fewer (functional) adipocytes, and increased visceral adiposity accompanied by functional endocrine and immune abnormalities. This helps explain the increased CVD risk factors and increased CVD risk among this unique population. These CVD risk factors include increased prevalence of metabolic syndrome (even at lower body mass index relative to other races), insulin resistance, type 2 diabetes mellitus, increased lipoprotein (a), and adiposopathic dyslipidemia [(i.e., elevated triglyceride levels, reduced high density lipoprotein cholesterol levels, increased low density lipoprotein (LDL) particle number, and increased prevalence of smaller and denser LDL particles]. Conclusion The four panelists of this roundtable discussion describe their practical diagnostic processes and treatment plans for patients from South Asia, with an emphasis on a patient-centered approach to obesity in this unique population.
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Affiliation(s)
- Harold Edward Bays
- Diplomate of American Board of Obesity Medicine, Medical Director/President Louisville Metabolic and Atherosclerosis Research Center, Clinical Associate Professor/University of Louisville Medical School, 3288 Illinois Avenue, Louisville, KY, 40213, USA
| | - Amardeep Shrestha
- Diplomate American Board of Obesity Medicine, Family Medical Clinic, Internal Medicine, Primary Care and Obesity Medicine, 1480 N Green Mount Road # 200, O'Fallon, IL, 62269, USA
| | - Varalakshmi Niranjan
- Diplomate of American Board of Obesity Medicine Assistant Professor, Division of Internal Medicine, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT, 06032, USA
| | - Monu Khanna
- Diplomate American Board of Obesity Medicine, Internal Medicine, Extended Care and Rehabilitation Services, VA St Louis Health Care System, Jefferson Barracks Division, 1 Jefferson Barracks Drive, St Louis, MO, 63125, USA
| | - Lalitha Kambhamettu
- Internal Medicine, Diplomate of American Board of Obesity Medicine, Wilmington VA Medical Center, 1601 Kirkwood Highway, Wilmington, DE, 19805, USA
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Blüher M, Müller-Wieland D. Editorial: Adipose tissue dysfunction. Front Endocrinol (Lausanne) 2022; 13:999188. [PMID: 36060968 PMCID: PMC9428705 DOI: 10.3389/fendo.2022.999188] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital, Leipzig, Germany
- Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
- *Correspondence: Matthias Blüher, ; Dirk Müller-Wieland,
| | - Dirk Müller-Wieland
- Department of Cardiology, Angiology and Intensive Care Medicine, University Hospital Aachen, Aachen, Germany
- *Correspondence: Matthias Blüher, ; Dirk Müller-Wieland,
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Asbaghi O, Naeini F, Ashtary-Larky D, Moradi S, Zakeri N, Eslampour E, Kelishadi MR, Naeini AA. Effects of chromium supplementation on lipid profile in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of randomized controlled trials. J Trace Elem Med Biol 2021; 66:126741. [PMID: 33813266 DOI: 10.1016/j.jtemb.2021.126741] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/27/2021] [Accepted: 03/04/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The purpose of this study was to determine the influence of chromium supplementation on lipid profile in patients with type 2 diabetes mellitus (T2DM). METHODS A systematic search was performed in Scopus, Embase, Web of Science, the Cochrane library and PubMed databases to find randomized controlled trials (RCTs) related to the effect of chromium supplementation on lipid profile in patients with T2DM, up to June 2020. Meta-analyses were performed using the random-effects model, and I2 index was used to evaluate heterogeneity. RESULTS The primary search yielded 725 publications. 24 RCTs (with 28 effect size) were eligible. Our meta-analysis indicated that chromium supplementation resulted in a significant decrease in serum levels of triglyceride (TG) (MD: -6.54 mg/dl, 95 % CI: -13.08 to -0.00, P = 0.050) and total cholesterol (TC) (WMD: -7.77 mg/dl, 95 % CI: -11.35 to -4.18, P < 0.001). Furthermore, chromium significantly increases high-density lipoprotein (HDL) (WMD: 2.23 mg/dl, 95 % CI: 0.07-4.40, P = 0.043) level. However, chromium supplementation did not have significant effects on low-density lipoprotein (LDL) (WMD: -8.54 mg/dl, 95 % CI: -19.58 to 2.49, P = 0.129) level. CONCLUSION Chromium supplementation may significantly improve lipid profile in patients with T2DM by decreasing TG and TC and increasing HDL. However, based on our analysis, chromium failed to affect LDL. It should be noted that the lipid-lowering properties of chromium supplementation were small and may not reach clinical importance.
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Affiliation(s)
- Omid Asbaghi
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
| | - Damoon Ashtary-Larky
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sajjad Moradi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran; Halal Research Centre of IRI, FDA, Tehran, Iran
| | - Nazanin Zakeri
- Nutrition Research Center, Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Eslampour
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Mahnaz Rezaei Kelishadi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirmansour Alavi Naeini
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
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Saxena A, Mathur N, Tiwari P, Mathur SK. Whole transcriptome RNA-seq reveals key regulatory factors involved in type 2 diabetes pathology in peripheral fat of Asian Indians. Sci Rep 2021; 11:10632. [PMID: 34017037 PMCID: PMC8137704 DOI: 10.1038/s41598-021-90148-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/06/2021] [Indexed: 01/04/2023] Open
Abstract
The prevalence of Type 2 Diabetes has reached an epidemic proportion particularly in south Asian countries. We have earlier shown that the anatomical fat distribution, termed 'thin fat phenotype' in this population indeed plays a major role for their T2D-predisposition it is indeed the sick fat or adiposopathy, which is the root cause of metabolic syndrome and diabetes and affects both-peripheral, as well as visceral adipose tissue compartments. In present study, we have attempted to unravel the altered regulatory mechanisms at the level of transcription factors, and miRNAs those may likely accounts to T2D pathophysiology in femoral subcutaneous adipose tissue. We prioritized transcription factors and protein kinases as likely upstream regulators of obtained differentially expressed genes in this RNA-seq study. An inferred network of these upstream regulators was then derived and the role of TFs and miRNAs in T2D pathophysiology was explored. In conclusions, this RNS-Seq study finds that peripheral subcutaneous adipose tissue among Asian Indians show pathology characterized by altered lipid, glucose and protein metabolism, adipogenesis defect and inflammation. A network of regulatory transcription factors, protein kinases and microRNAs have been imputed which converge on the process of adipogenesis. As the majority of these genes also showed altered expression in diabetics and some of them are also circulatory, therefore they deserve further investigation for potential clinical diagnostic and therapeutic applications.
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Affiliation(s)
- Aditya Saxena
- Department of Computer Engineering and Applications, Institute of Engineering and Technology, GLA University, Mathura, 281406, India
| | - Nitish Mathur
- Department of Endocrinology, Sawai Man Singh Medical College and Hospital, Jaipur, 302004, India
| | - Pradeep Tiwari
- Department of Endocrinology, Sawai Man Singh Medical College and Hospital, Jaipur, 302004, India
- Department of Chemistry, School of Basic Sciences, Manipal University Jaipur, Jaipur, 303007, India
| | - Sandeep Kumar Mathur
- Department of Endocrinology, Sawai Man Singh Medical College and Hospital, Jaipur, 302004, India.
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Guolla L, Morrison KM, Barr RD. Adiposity in Survivors of Cancer in Childhood: How is it Measured and Why Does it Matter? J Pediatr Hematol Oncol 2021; 43:1-11. [PMID: 33122586 DOI: 10.1097/mph.0000000000001988] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Survival of cancer in childhood is increasingly common with modern therapeutic protocols but leads frequently to adverse long-term impacts on health, including metabolic and cardiovascular disease. Changes in body composition, especially an increase in fat mass and a decrease in muscle mass, are found early in patients with pediatric cancer, persist long after treatment has been completed and seem to contribute to the development of chronic disease. This review details the effects of such changes in body composition and reviews the underlying pathophysiology of the development of sarcopenic obesity and its adverse metabolic impact. The authors discuss the particular challenges in identifying obesity accurately in survivors of pediatric cancer using available measurement techniques, given that common measures, such as body mass index, do not distinguish between muscle and adipose tissue or assess their distribution. The authors highlight the importance of a harmonized approach to the assessment of body composition in pediatric cancer survivors and early identification of risk using "gold-standard" measurements. This will improve our understanding of the significance of adiposity and sarcopenia in this population, help identify thresholds predictive of metabolic risk, and ultimately prevent or ameliorate the long-term metabolic and cardiovascular impacts on health experienced by survivors of cancer in childhood.
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Affiliation(s)
| | - Katherine M Morrison
- Department of Pediatrics, McMaster University
- McMaster Children's Hospital, Hamilton Health Sciences, Hamilton, ON, Canada
| | - Ronald D Barr
- Department of Pediatrics, McMaster University
- McMaster Children's Hospital, Hamilton Health Sciences, Hamilton, ON, Canada
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Obesity Indices to Use for Identifying Metabolic Syndrome among Rural Adults in South Africa. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17228321. [PMID: 33187051 PMCID: PMC7696649 DOI: 10.3390/ijerph17228321] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/03/2020] [Accepted: 07/05/2020] [Indexed: 01/16/2023]
Abstract
Metabolic syndrome (MetS) is a cluster of metabolic conditions that aggravate the likelihood of cardiovascular diseases and type 2 diabetes mellitus. This study was aimed to identify the best obesity index to determine MetS. This was a cross-sectional study and part of the Ellisras Longitudinal Study where 593 (289 males and 304 females) adults aged 22–30 years took part. Confirmatory factor analysis was used to test the single-factor models of MetS defined by mid arterial pressure, fasting blood glucose, triglycerides and commonly selected obesity indices such as Neck circumference (NC), Body mass index (BMI), Waist circumference (WC) and Waist to height ratio (WHtR) as indicators of MetS. It was found that a single model fit built based on WC and WHtR suggested a better fit index than NC and BMI in males, whereas, a model built on NC obtained a better fit index for females than other factor models. In conclusion, the result of the present study suggests that in rural Ellisras adult’s, WC and WHtR are the best obesity indices for determining MetS in males and NC in females than other indices. Hence, longitudinal studies are recommended to allow causality to be drawn between obesity indices and MetS.
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The Transcriptomic Evidence on the Role of Abdominal Visceral vs. Subcutaneous Adipose Tissue in the Pathophysiology of Diabetes in Asian Indians Indicates the Involvement of Both. Biomolecules 2020; 10:biom10091230. [PMID: 32847136 PMCID: PMC7563456 DOI: 10.3390/biom10091230] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/28/2020] [Accepted: 08/18/2020] [Indexed: 12/14/2022] Open
Abstract
The roles of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) in the molecular pathogenesis type-2 diabetics (T2D) among Asian Indians showing a "thin fat" phenotype largely remains obscure. In this study, we generated transcription profiles in biopsies of these adipose depots obtained during surgery in 19 diabetics (M: F ratio, 8:11) and 16 (M: F ratio 5:11) age- and BMI-matched non-diabetics. Gene set enrichment analysis (GSEA) was used for comparing transcription profile and showed that 19 gene sets, enriching inflammation and immune system-related pathways, were upregulated in diabetics with F.D.R. <25% and >25%, respectively, in VAT and SAT. Moreover, 13 out of the 19 significantly enriched pathways in VAT were among the top 20 pathways in SAT. On comparison of VAT vs. SAT among diabetics, none of the gene sets were found significant at F.D.R. <25%. The Weighted Gene Correlation Analysis (WGCNA) analysis of the correlation between measures of average gene expression and overall connectivity between VAT and SAT was significantly positive. Several modules of co-expressed genes in both the depots showed a bidirectional correlation with various diabetes-related intermediate phenotypic traits. They enriched several diabetes pathogenicity marker pathways, such as inflammation, adipogenesis, etc. It is concluded that, in Asian Indians, diabetes pathology inflicts similar molecular alternations in VAT and SAT, which are more intense in the former. Both adipose depots possibly play a role in the pathophysiology of T2D, and whether it is protective or pathogenic also depends on the nature of modules of co-expressed genes contained in them.
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15
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Zhang L, Yuan M, An Z, Zhao X, Wu H, Li H, Wang Y, Sun B, Li H, Ding S, Zeng X, Chao L, Li P, Wu W. Prediction of hypertension, hyperglycemia and dyslipidemia from retinal fundus photographs via deep learning: A cross-sectional study of chronic diseases in central China. PLoS One 2020; 15:e0233166. [PMID: 32407418 PMCID: PMC7224473 DOI: 10.1371/journal.pone.0233166] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Accepted: 04/29/2020] [Indexed: 12/31/2022] Open
Abstract
Retinal fundus photography provides a non-invasive approach for identifying early microcirculatory alterations of chronic diseases prior to the onset of overt clinical complications. Here, we developed neural network models to predict hypertension, hyperglycemia, dyslipidemia, and a range of risk factors from retinal fundus images obtained from a cross-sectional study of chronic diseases in rural areas of Xinxiang County, Henan, in central China. 1222 high-quality retinal images and over 50 measurements of anthropometry and biochemical parameters were generated from 625 subjects. The models in this study achieved an area under the ROC curve (AUC) of 0.880 in predicting hyperglycemia, of 0.766 in predicting hypertension, and of 0.703 in predicting dyslipidemia. In addition, these models can predict with AUC>0.7 several blood test erythrocyte parameters, including hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and a cluster of cardiovascular disease (CVD) risk factors. Taken together, deep learning approaches are feasible for predicting hypertension, dyslipidemia, diabetes, and risks of other chronic diseases.
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Affiliation(s)
- Li Zhang
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Mengya Yuan
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Zhen An
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Xiangmei Zhao
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Hui Wu
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Haibin Li
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Ya Wang
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Beibei Sun
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Huijun Li
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Shibin Ding
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Xiang Zeng
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Ling Chao
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Pan Li
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
- * E-mail: (PL); (WW)
| | - Weidong Wu
- School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
- * E-mail: (PL); (WW)
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Heiston EM, Eichner NZ, Gilbertson NM, Malin SK. Exercise improves adiposopathy, insulin sensitivity and metabolic syndrome severity independent of intensity. Exp Physiol 2020; 105:632-640. [PMID: 32020676 DOI: 10.1113/ep088158] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 01/20/2020] [Indexed: 12/16/2022]
Abstract
NEW FINDINGS What is the central question of this study? What are the effects of work-matched continuous versus high-intensity interval training for 2 weeks on adiposopathy and cardiometabolic risk in obese adults with prediabetes? What is the main finding and its importance? Independent of intensity, short-term exercise improves adiposopathy and insulin sensitivity. While both exercise intensities reduced fasting leptin concentrations and metabolic syndrome severity, only interval training elevated total adiponectin. In contrast to previous work, neither condition altered high-molecular weight adiponectin. Collectively, these data suggest that short-term exercise can improve adipokine profiles, which may aid in reducing cardiometabolic risk prior to clinically meaningful weight loss in adults with prediabetes. ABSTRACT Individuals with prediabetes who are overweight and obese are at an increased risk of developing endocrine disruption of fat tissue, known as adiposopathy. While short-term exercise improves adipokine profiles, the effects of exercise intensity when matched for energy expenditure on adiposopathy are unknown. We hypothesized that high-intensity exercise would elicit greater changes in adiposopathy compared to moderate exercise. Twenty-eight overweight and obese adults (age: 60.9 ± 8.4 years; BMI: 33.0 ± 5.4 kg m-2 ) with prediabetes were randomized to twelve 60-min sessions of either moderate-continuous (CONT; n = 14) or high-intensity interval (INT; n = 14) exercise training. Total and high molecular weight (HMW) adiponectin and leptin were collected to assess adiposopathy (ratio of total adiponectin to leptin; A/L). Insulin sensitivity (SIIS ) was determined using a 75 g oral glucose tolerance test before and after training. Cardiometabolic risk factors were measured and a z-score was calculated to determine metabolic syndrome (MetS) severity. CONT and INT increased A/L (P < 0.01) and decreased leptin (P < 0.01) and MetS severity (P = 0.04). Neither intervention altered circulating levels of HMW adiponectin (P = 0.76) and only INT increased total adiponectin levels (P = 0.02). Both intensities increased insulin sensitivity (P < 0.01), which was associated with improvements in A/L (r = 0.47, P = 0.01). Additionally, increases in A/L tended to relate to decreased MetS severity (r = -0.36, P = 0.09). Short-term exercise intensity, when matched for energy expenditure, does not differentially affect improvements in adiposopathy in overweight and obese adults with prediabetes. Further, 12 bouts of exercise improved insulin sensitivity and MetS severity, suggesting that improving adipokine profiles may aid in reducing cardiometabolic risk.
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Affiliation(s)
- Emily M Heiston
- Department of Kinesiology, University of Virginia, Charlottesville, VA, USA
| | - Natalie Zm Eichner
- Department of Kinesiology, University of Virginia, Charlottesville, VA, USA
| | | | - Steven K Malin
- Department of Kinesiology, University of Virginia, Charlottesville, VA, USA
- Division of Endocrinology & Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA, USA
- Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA
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17
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Saxena A, Sachin K. A Network Biology Approach for Assessing the Role of Pathologic Adipose Tissues in Insulin Resistance Using Meta-analysis of Microarray Datasets. Curr Genomics 2018; 19:630-666. [PMID: 30386174 PMCID: PMC6194434 DOI: 10.2174/1389202919666180726125645] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 05/10/2018] [Accepted: 07/16/2018] [Indexed: 11/22/2022] Open
Abstract
Background The role of adipose tissue in Insulin resistance (IR) and Type 2 Diabetes (T2D) has well been received in the biomedical community; being a precursor of T2D, identification of the molecular basis of IR is therefore, vital to elucidate T2D- pathogenesis and meta-analysis of previously conducted microarray studies provides an inexpensive approach to achieve this end. Methods In this study, we have carried out a statistical meta-analysis of 157 microarray datasets from five independent studies and identified a meta-signature of 1,511 genes; their functional meaning was elucidated by integrated pathways-analysis. Further, a protein-protein interaction network was constructed and key genes along with their high confidence transcriptional- and epigenetic-mediators were identified using a network biology approach. Results Various inflammation- and immune system-related pathways such as TGF-β signaling, IL7 signaling, Neutrophil degranulation, and Chemokine signaling etc. were enriched in sick adipose tissues; identified transcription factors, and microRNAs were also found to regulate processes relevant to IR/T2D pathophysiology. Conclusion This study endorses the development of effective bioinformatics workflow and further grants an indication for the acceptance of adiposopathy as the root mechanistic pathology that poses risk for development of type 2 diabetes; concept of adipospathy in place of metabolic syndrome will open the possibility to design drugs, those will ameliorate adipose functions and hence proved to be more effective against Type 2 Diabetes.
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Affiliation(s)
- Aditya Saxena
- 1Department of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura (U.P.), India; 2Uttarakhand Technical University, Dehradun (U.K.), India; 3Department of Biochemistry and Biotechnology, S.B.S. (PG) Institute of Biomedical Sciences & Research, Dehradun (U.K.), India
| | - Kumar Sachin
- 1Department of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura (U.P.), India; 2Uttarakhand Technical University, Dehradun (U.K.), India; 3Department of Biochemistry and Biotechnology, S.B.S. (PG) Institute of Biomedical Sciences & Research, Dehradun (U.K.), India
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18
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Kouli GM, Panagiotakos DB, Kyrou I, Georgousopoulou EN, Chrysohoou C, Tsigos C, Tousoulis D, Pitsavos C. Visceral adiposity index and 10-year cardiovascular disease incidence: The ATTICA study. Nutr Metab Cardiovasc Dis 2017; 27:881-889. [PMID: 28851556 DOI: 10.1016/j.numecd.2017.06.015] [Citation(s) in RCA: 104] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 05/11/2017] [Accepted: 06/26/2017] [Indexed: 11/25/2022]
Abstract
BACKGROUND AND AIMS Visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue accumulation/dysfunction. Our aim was to evaluate potential associations between the VAI and the 10-year cardiovascular disease (CVD) incidence. METHODS AND RESULTS During 2001-2002, 3042 Greek adults (1514 men; age: ≥18 years) without previous CVD were recruited into the ATTICA study, whilst the 10-year study follow-up was performed in 2011-2012, recording the fatal/non-fatal CVD incidence in 2020 (1010 men) participants. The baseline VAI scores for these participants were calculated based on anthropometric and lipid variables, while VAI tertiles were extracted for further analyses. During the study follow-up a total of 317 CVD events (15.7%) were observed. At baseline, the participants' age and the prevalence of hypertension, diabetes, hypercholesterolemia and metabolic syndrome increased significantly across the VAI tertiles. After adjusting for multiple confounders, VAI exhibited a significantly independent positive association with the 10-year CVD incidence (OR = 1.05, 95%CI: 1.01, 1.10), whereas the association of the body mass index (HR = 1.03, 95%CI: 0.99, 1.08), or the waist circumference (HR = 1.01, 95%CI: 0.99, 1.02) was less prominent. Sex-specific analysis further showed that VAI remained significantly predictive of CVD in men alone (HR = 1.06, 95%CI: 1.00, 1.11) but not in women (HR = 1.06, 95%CI: 0.96, 1.10). CONCLUSIONS Our findings show for the first time in a large-sample, long-term, prospective study in Europe that the VAI is independently associated with elevated 10-year CVD risk, particularly in men. This suggests that the VAI may be utilized as an additional indicator of long-term CVD risk for Caucasian/Mediterranean men without previous CVD.
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Affiliation(s)
- G-M Kouli
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - D B Panagiotakos
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
| | - I Kyrou
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Aston Medical Research Institute, Aston Medical School, Aston University, B4 7ET Birmingham, UK; WISDEM, University Hospital Coventry and Warwickshire NHS Trust, CV2 2DX Coventry, UK; Translational & Experimental Medicine, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, CV4 7AL Coventry, UK
| | - E N Georgousopoulou
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - C Chrysohoou
- First Cardiology Clinic, School of Medicine, University of Athens, Greece
| | - C Tsigos
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - D Tousoulis
- First Cardiology Clinic, School of Medicine, University of Athens, Greece
| | - C Pitsavos
- First Cardiology Clinic, School of Medicine, University of Athens, Greece
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19
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Abdolali B, Mojtaba E, Shahram S, Heshmatollah P, Mohammadali S. Adiponectin/TNF-α Ratio Following a Selected Aerobic Training in Sedentary Adult Obese Men. AVICENNA JOURNAL OF MEDICAL BIOCHEMISTRY 2017. [DOI: 10.15171/ajmb.2017.05] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background: Based on clinical studies, low adiponectin and high tumor necrosis factor alpha (TNF-α) are associated with obesity and related diseases such as type 2 diabetes and insulin resistance. Objectives: In this study, we aimed to investigate the effect of an aerobic training program on adiponectin, TNF-α, and adiponectin/TNF-α ratio in adult obese men. Patients and Methods: For this purpose, 24 sedentary adult obese men matched for age (38 ± 3.23 years) and body mass index (31.94 ± 3.26 kg/m2 ) were selected and divided into exercise (aerobic training) and control groups. Exercise subjects participated in an aerobic exercise training intervention for 12 weeks (3 times/week) and the control group did not participate in aerobic intervention. Anthropometric and biochemical data including fasting serum adiponectin, TNF-α, and adiponectin/TNF-α ratio were measured before and after aerobic training for each participant in each group. Data were analyzed by both independent and paired sample t test. Results: Compared to pre-training, fasting serum adiponectin decreased significantly (P = .019), but serum TNF-α was not changed by aerobic training (P = .057). A significant increase was observed in adiponectin/TNF-α ratio in exercise subjects after aerobic training (P = .008). Conclusions: Based on these data, we conclude that aerobic training intervention is associated with improved inflammatory profile in obese subjects.
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Affiliation(s)
- Banaeifar Abdolali
- Assistant Professor of Exercise Physiology, South Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Eizadi Mojtaba
- Assistant Professor of Exercise Physiology, Saveh Branch, Islamic Azad University, Saveh, Iran
| | - Sohaily Shahram
- Assistant Professor of Exercise Physiology, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran
| | - Parsyan Heshmatollah
- Assistant Professor of Exercise Physiology, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran
| | - Sayedhossainii Mohammadali
- Master of Sciences of Physical Education and Sport Sciences, Parand Branch, Islamic Azad University, Tehran, Iran
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20
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Alvero-Cruz JR, Fernández Vázquez R, García Vega MDM, García Lavigne JA, Rodríguez Linares MV, Martínez Blanco J. [Sensitivity and specificity of abdominal adiposity with metabolic syndrome in the elderly]. Rev Esp Geriatr Gerontol 2017; 52:128-134. [PMID: 28012616 DOI: 10.1016/j.regg.2016.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Revised: 10/26/2016] [Accepted: 11/03/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVES It is recognised that abdominal adiposity is associated with cardiovascular risk factors, such as intolerance to glucose, hypertension and dyslipidaemia. The objective of the present study was to assess the relationship of trunk fat and visceral fat index, obtained by anthropometric and bioelectrical impedance, with metabolic syndrome (SM) in an elderly population. METHODS The study included 208 subjects (78 men and 130 women) with a mean age of 82.5 years. Abdominal obesity was assessed by anthropometry and bioelectrical impedance. ROC curves were calculated in order to assess the ability of these variables to diagnose metabolic syndrome. RESULTS There are differences between men and women in body mass index, waist to height ratio, waist circumference, and bioelectrical impedance measurements as trunk fat and visceral fat (p<.05). Also, found differences in anthropometric indices and variables and abdominal bioelectrical impedance between subjects with and without SM (p<.05) and only exist differences in blood glucose, triglycerides and HDL cholesterol (p<.05). There are significant correlations between anthropometric variables and abdominal bioelectrical impedance (p<.05). Areas under the curve (AUC) of waist to height index, waist circumference, sagittal abdominal diameter, and trunk fat were greater than 0.8 (all p<.01), and in women did not exceed values of 0.65. The cut-off points obtained for BMI were 26.81 and 23.53kg/m2, 102 and 91cm for waist circumference, 22.1 and 20.7cm for sagittal abdominal diameter, 34% and 43.7% for trunk fat, and 17 and 11.5 for visceral fat ratio in men and women, respectively. CONCLUSIONS There are different levels of predictive ability for metabolic syndrome according to gender. Trunk fat and visceral fat index and anthropometric measures have higher predictive ability for metabolic syndrome in men than in women.
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Affiliation(s)
- José Ramón Alvero-Cruz
- Departamento de Fisiología Humana, Histología, Anatomía Patológica y Educación Física y Deportiva, Facultad de Medicina, Universidad de Málaga Andalucía Tech., Málaga, España; Instituto de Investigaciones Biomédicas de Málaga, Málaga, España.
| | - Rosalía Fernández Vázquez
- Departamento de Fisiología Humana, Histología, Anatomía Patológica y Educación Física y Deportiva, Facultad de Medicina, Universidad de Málaga Andalucía Tech., Málaga, España
| | | | | | | | - Javier Martínez Blanco
- Unidad de Residencias del Distrito Sanitario Costa del Sol, Consejería de Salud de la Junta de Andalucía-Málaga, Málaga, España
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Fitness, adiposopathy, and adiposity are independent predictors of insulin sensitivity in middle-aged men without diabetes. J Physiol Biochem 2016; 72:435-44. [PMID: 27139423 DOI: 10.1007/s13105-016-0488-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 04/12/2016] [Indexed: 10/21/2022]
Abstract
Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI] <25 kg/m(2)), sedentary with obesity (BMI > 30 kg/m(2)), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = -0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R (2) = 0.61). While adiposopathy was also an independent and significant contributor (partial R (2) = 0.10), waist circumference added little power to the model (partial R (2) = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes.
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De Lorenzo A, Soldati L, Sarlo F, Calvani M, Di Lorenzo N, Di Renzo L. New obesity classification criteria as a tool for bariatric surgery indication. World J Gastroenterol 2016; 22:681-703. [PMID: 26811617 PMCID: PMC4716069 DOI: 10.3748/wjg.v22.i2.681] [Citation(s) in RCA: 170] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 10/05/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy (‘‘sick fat’’) clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described: (1) normal weight obese (NWO); (2) metabolically obese normal weight; (3) metabolically healthy obese; and (4) metabolically unhealthy obese or “at risk” obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention.
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Bays HE, Jones PH, Jacobson TA, Cohen DE, Orringer CE, Kothari S, Azagury DE, Morton J, Nguyen NT, Westman EC, Horn DB, Scinta W, Primack C. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT. J Clin Lipidol 2016; 10:33-57. [DOI: 10.1016/j.jacl.2015.12.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023]
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GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance. PLoS One 2014; 9:e109540. [PMID: 25299671 PMCID: PMC4192353 DOI: 10.1371/journal.pone.0109540] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2014] [Accepted: 09/10/2014] [Indexed: 01/26/2023] Open
Abstract
Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhood obesity, hyperinsulinemia, and type 2 diabetes. Here we investigated the role of Alms1 disruption in AT expansion and insulin responsiveness in a murine model for Alström Syndrome. A gene trap insertion in Alms1 on the insulin sensitive C57BL6/Ei genetic background leads to early hyperinsulinemia and a progressive increase in body weight. At 6 weeks of age, before the onset of the metabolic disease, the mutant mice had enlarged fat depots with hypertrophic adipocytes, but without signs of inflammation. Expression of lipogenic enzymes was increased. Pre-adipocytes isolated from mutant animals demonstrated normal adipogenic differentiation but gave rise to mature adipocytes with reduced insulin-stimulated glucose uptake. Assessment of whole body glucose homeostasis revealed glucose intolerance. Insulin stimulation resulted in proper AKT phosphorylation in adipose tissue. However, the total amount of glucose transporter 4 (SLC4A2) and its translocation to the plasma membrane were reduced in mutant adipose depots compared to wildtype littermates. Alterations in insulin stimulated trafficking of glucose transporter 4 are an early sign of metabolic dysfunction in Alström mutant mice, providing a possible explanation for the reduced glucose uptake and the compensatory hyperinsulinemia. The metabolic signaling deficits either reside downstream or are independent of AKT activation and suggest a role for ALMS1 in GLUT4 trafficking. Alström mutant mice represent an interesting model for the development of metabolic disease in which adipose tissue with a reduced glucose uptake can expand by de novo lipogenesis to an obese state.
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Gonzalez-Campoy JM, Richardson B, Richardson C, Gonzalez-Cameron D, Ebrahim A, Strobel P, Martinez T, Blaha B, Ransom M, Quinonez-Weislow J, Pierson A, Gonzalez Ahumada M. Bariatric endocrinology: principles of medical practice. Int J Endocrinol 2014; 2014:917813. [PMID: 24899894 PMCID: PMC4036612 DOI: 10.1155/2014/917813] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 03/19/2014] [Accepted: 04/11/2014] [Indexed: 12/11/2022] Open
Abstract
Obesity, is a chronic, biological, preventable, and treatable disease. The accumulation of fat mass causes physical changes (adiposity), metabolic and hormonal changes due to adipose tissue dysfunction (adiposopathy), and psychological changes. Bariatric endocrinology was conceived from the need to address the neuro-endocrinological derangements that are associated with adiposopathy, and from the need to broaden the scope of the management of its complications. In addition to the well-established metabolic complications of overweight and obesity, adiposopathy leads to hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, dysregulation of gut peptides including GLP-1 and ghrelin, the development of an inflammatory milieu, and the strong risk of vascular disease. Therapy for adiposopathy hinges on effectively lowering the ratio of orexigenic to anorexigenic signals reaching the the hypothalamus and other relevant brain regions, favoring a lower caloric intake. Adiposopathy, overweight and obesity should be treated indefinitely with the specific aims to reduce fat mass for the adiposity complications, and to normalize adipose tissue function for the adiposopathic complications. This paper defines the principles of medical practice in bariatric endocrinology-the treatment of overweight and obesity as means to treat adiposopathy and its accompanying metabolic and hormonal derangements.
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Affiliation(s)
- J. Michael Gonzalez-Campoy
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Bruce Richardson
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Conor Richardson
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - David Gonzalez-Cameron
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Ayesha Ebrahim
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Pamela Strobel
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Tiphani Martinez
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Beth Blaha
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Maria Ransom
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Jessica Quinonez-Weislow
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Andrea Pierson
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
| | - Miguel Gonzalez Ahumada
- Minnesota Center for Obesity, Metabolism and Endocrinology (MNCOME), 1185 Town Centre Drive, Suite 220, Eagan, MN 55123, USA
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Abstract
Among lean populations, cardiovascular disease (CVD) is rare. Among those with increased adiposity, CVD is the commonest cause of worldwide death. The "obesity paradox" describes seemingly contrary relationships between body fat and health/ill-health. Multiple obesity paradoxes exist, and include the anatomic obesity paradox, physiologic obesity paradox, demographic obesity paradox, therapeutic obesity paradox, cardiovascular event/procedure obesity paradox, and obesity treatment paradox. Adiposopathy ("sick fat") is defined as adipocyte/adipose tissue dysfunction caused by positive caloric balance and sedentary lifestyle in genetically and environmentally susceptible individuals. Adiposopathy contributes to the commonest metabolic disorders encountered in clinical practice (high glucose levels, high blood pressure, dyslipidemia, etc.), all major CVD risk factors. Ockham's razor is a principle of parsimony which postulates that among competing theories, the hypothesis with the fewest assumptions is the one best selected. Ockham's razor supports adiposopathy as the primary cause of most cases of adiposity-related metabolic diseases, which in turn helps resolve the obesity paradox.
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Affiliation(s)
- Harold Bays
- Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY, 40213, USA,
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Amato MC, Pizzolanti G, Torregrossa V, Misiano G, Milano S, Giordano C. Visceral adiposity index (VAI) is predictive of an altered adipokine profile in patients with type 2 diabetes. PLoS One 2014; 9:e91969. [PMID: 24651545 PMCID: PMC3961281 DOI: 10.1371/journal.pone.0091969] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Accepted: 02/15/2014] [Indexed: 02/08/2023] Open
Abstract
Aims Although there is still no clear definition of “adipose tissue dysfunction” or ATD, the identification of a clinical marker of altered fat distribution and function may provide the needed tools for early identification of a condition of cardiometabolic risk. Our aim was to evaluate the correlations among various anthropometric indices [BMI, Waist Circumference (WC), Hip Circumference (HC), Waist/Hip ratio (WHR), Body Adiposity Index (BAI) and Visceral adiposity Index (VAI)] and several adipocytokines [Visfatin, Resistin, Leptin, Soluble leptin receptors (sOB-R), Adiponectin, Ghrelin, Adipsin, PAI-1, vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF) TNF-α, hs-CRP, IL-6, IL-18] in patients with type 2 diabetes (DM2). Materials and Methods Ninety-one DM2 patients (age: 65.25±6.38 years; 42 men and 49 women) in stable treatment for the last six months with metformin in monotherapy (1.5–2 g/day) were cross-sectionally studied. Clinical, anthropometric, and metabolic parameters were evaluated. Serum adipocytokine levels were assayed with Luminex based kits. Results At the Pearson’s correlation, among all the indices investigated, VAI showed a significant correlation with almost all adipocytokines analyzed [Visfatin, Resistin and hsCRP (all p<0.001); Adiponectin, sOb-R, IL-6, IL-18, HGF (all p<0.010); Ghrelin and VEGF (both p<0.05)]. Through a two-step cluster analysis, 55 patients were identified with the most altered adipocytokine profile (patients with ATD). At a ROC analysis, VAI showed the highest C-statistic [0.767 (95% CI 0.66–0.84)] of all the indices. Conclusions Our study suggests that the VAI, among the most common indexes of adiposity assessment, shows the best correlation with the best known adipocytokines and cardiometabolic risk serum markers. Although to date we are still far from clearly identifying an ATD, the VAI would be an easy tool for clearly mirroring a condition of cardiometabolic risk, in the absence of an overt metabolic syndrome.
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Affiliation(s)
- Marco C. Amato
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), Section of Endocrinology, Diabetology and Metabolism, University of Palermo, Palermo, Italy
| | - Giuseppe Pizzolanti
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), Section of Endocrinology, Diabetology and Metabolism, University of Palermo, Palermo, Italy
| | - Vittoria Torregrossa
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), Section of Endocrinology, Diabetology and Metabolism, University of Palermo, Palermo, Italy
| | - Gabriella Misiano
- Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi (Di.Bi.Me.F), Section of Clinical Pathology, University of Palermo, Palermo, Italy
| | - Salvatore Milano
- Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi (Di.Bi.Me.F), Section of Clinical Pathology, University of Palermo, Palermo, Italy
| | - Carla Giordano
- Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), Section of Endocrinology, Diabetology and Metabolism, University of Palermo, Palermo, Italy
- * E-mail:
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Vest AR, Young JB. Should we target obesity in advanced heart failure? CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2014; 16:284. [PMID: 24482160 DOI: 10.1007/s11936-013-0284-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OPINION STATEMENT Obesity is a risk factor for the development of heart failure (HF), but has been associated with improved survival in patients with established HF. Weight loss should clearly be recommended and supported for obese individuals without cardiac pathology to prevent cardiomyopathy development. Clinical recommendations at the other end of the obesity heart failure spectrum are also relatively clear. Morbidly obese individuals (BMI ≥ 40 kg/m(2)) aged <50 years with severely depressed systolic function and NYHA class III-IV symptoms should be considered for malabsorptive bariatric surgery at an experienced center. The goal is either improved systolic function and symptoms, or sufficient weight loss for heart transplant eligibility. Recommendations for patients falling between these extremes are more challenging. Overweight and mildly obese HF patients (25-35 kg/m(2)) may be somewhat protected from cardiac cachexia and weight loss is not expected to enhance survival, but may offer symptomatic benefits.
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Affiliation(s)
- Amanda R Vest
- Heart and Vascular Institute, Section of Heart Failure, 9500 Euclid Avenue, Mail Code J3-4, Cleveland, OH, 44195, USA,
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Bays HE. Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development. Expert Rev Cardiovasc Ther 2014; 9:265-77. [DOI: 10.1586/erc.10.22] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Bays H. Adiposopathy, metabolic syndrome, quantum physics, general relativity, chaos and the Theory of Everything. Expert Rev Cardiovasc Ther 2014; 3:393-404. [PMID: 15889967 DOI: 10.1586/14779072.3.3.393] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Excessive fat (adiposity) and dysfunctional fat (adiposopathy) constitute the most common worldwide epidemics of our time -- and perhaps of all time. Ongoing efforts to explain how the micro (adipocyte) and macro (body organ) biologic systems interact through function and dysfunction in promoting Type 2 diabetes mellitus, hypertension and dyslipidemia are not unlike the mechanistic and philosophical thinking processes involved in reconciling the micro (quantum physics) and macro (general relativity) theories in physics. Currently, the term metabolic syndrome refers to a constellation of consequences often associated with excess body fat and is an attempt to unify the associations known to exist between the four fundamental metabolic diseases of obesity, hyperglycemia (including Type 2 diabetes mellitus), hypertension and dyslipidemia. However, the association of adiposity with these metabolic disorders is not absolute and the metabolic syndrome does not describe underlying causality, nor does the metabolic syndrome necessarily reflect any reasonably related pathophysiologic process. Just as with quantum physics, general relativity and the four fundamental forces of the universe, the lack of an adequate unifying theory of micro causality and macro consequence is unsatisfying, and in medicine, impairs the development of agents that may globally improve both obesity and obesity-related metabolic disease. Emerging scientific and clinical evidence strongly supports the novel concept that it is not adiposity alone, but rather it is adiposopathy that is the underlying cause of most cases of Type 2 diabetes mellitus, hypertension and dyslipidemia. Adiposopathy is a plausible Theory of Everything for mankind's greatest metabolic epidemics.
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Affiliation(s)
- Harold Bays
- L-MARC Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA.
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Bays HE, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 2014; 6:391-409. [DOI: 10.1586/14779072.6.3.391] [Citation(s) in RCA: 177] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Abstract
Elevated blood levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk for atherosclerotic coronary heart disease (CHD). Atorvastatin is a statin drug that inhibits 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (the rate-limiting step of cholesterol production) and primarily lowers LDL-C levels. Atorvastatin has also been shown to significantly reduce CHD events. However, as with all statins (and all other monotherapy lipid-altering drugs), atorvastatin alone reduces the risk of CHD in only a minority of patients relative to placebo. Conversely, it is low levels of high-density lipoprotein cholesterol that are associated with increased CHD risk. Torcetrapib is a cholesteryl ester transfer protein inhibitor that primarily raises high-density lipoprotein cholesterol levels, and cholesteryl ester transfer protein inhibition has generally been shown to reduce atherosclerosis in rabbits. Taken together, atorvastatin and torcetrapib provide striking improvements in lipid levels, and complementary actions upon important lipid parameters. This review examines the chemistry, mechanism of action, pharmacokinetics, metabolism, safety/tolerability and efficacy of the combination torcetrapib/atorvastatin agent that is currently in development and that provides complementary lipid benefits towards the goal of reducing CHD risk beyond that of atorvastatin alone.
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Affiliation(s)
- Harold Bays
- L-MARC Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA.
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Bays H. Phentermine, topiramate and their combination for the treatment of adiposopathy (‘sick fat’) and metabolic disease. Expert Rev Cardiovasc Ther 2014; 8:1777-801. [DOI: 10.1586/erc.10.125] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Bays HE. Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for ‘sick fat’ and metabolic disease. Expert Rev Cardiovasc Ther 2014; 7:1429-45. [DOI: 10.1586/erc.09.123] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Bays H, Blonde L, Rosenson R. Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients? Expert Rev Cardiovasc Ther 2014; 4:871-95. [PMID: 17173503 DOI: 10.1586/14779072.4.6.871] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
An increase in bodyweight is generally associated with an increased risk of excessive fat-related metabolic diseases (EFRMD), including Type 2 diabetes mellitus, hypertension and dyslipidemia. However, not all patients who are overweight have EFRMD, and not all patients with EFRMD are significantly overweight. The adipocentric paradigm provides the basis for a unifying, pathophysiological process whereby fat gain in susceptible patients leads to fat dysfunction ('sick fat'), and wherein pathological abnormalities in fat function (adiposopathy) are more directly related to the onset of EFRMD than increases in fat mass (adiposity) alone. But just as worsening fat function worsens EFRMD, improved fat function improves EFRMD. Peroxisome proliferator-activated receptor-gamma agonists increase the recruitment, proliferation and differentiation of preadipocytes ('healthy fat') and cause apoptosis of hypertrophic and dysfunctional (including visceral) adipocytes resulting in improved fat function and improved metabolic parameters associated with EFRMD. Weight loss interventions, such as a hypocaloric diet and physical exercise, in addition to agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may have favorable effects upon fat storage (lipogenesis and fat distribution), nutrient metabolism (such as free fatty acids), favorable effects upon adipose tissue factors involved in metabolic processes and inflammation, and enhanced 'cross-talk' with other major organ systems. In some cases, weight loss therapeutic agents may even affect metabolic parameters and adipocyte function independently of weight loss alone, suggesting that the benefit of these agents in improving EFRMD may go beyond their efficacy in weight reduction. This review describes how adiposopathy interventions may affect fat function, and thus improve EFRMD.
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Affiliation(s)
- Harold Bays
- L-MARC Research Center, Medical Director/President, 3288 Illinois Avenue, Louisville, KY 40213, USA.
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Mauro CR, Nguyen BT, Yu P, Tao M, Gao I, Seidman MA, Nguyen LL, Ozaki CK. Inflammatory "adiposopathy" in major amputation patients. Ann Vasc Surg 2013; 27:346-52. [PMID: 23498310 DOI: 10.1016/j.avsg.2012.07.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Revised: 07/11/2012] [Accepted: 07/16/2012] [Indexed: 11/25/2022]
Abstract
BACKGROUND Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation. METHODS AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression. RESULTS Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive. CONCLUSIONS AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes.
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Affiliation(s)
- Christine R Mauro
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
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Kanerva N, Kaartinen NE, Schwab U, Lahti-Koski M, Männistö S. Adherence to the Baltic Sea diet consumed in the Nordic countries is associated with lower abdominal obesity. Br J Nutr 2013; 109:520-8. [PMID: 22575060 DOI: 10.1017/s0007114512001262] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Due to differences in food cultures, dietary quality measures, such as the Mediterranean Diet Score, may not be easily adopted by other countries. Recently, the Baltic Sea Diet Pyramid was developed to illustrate healthy choices for the diet consumed in the Nordic countries. We assessed whether the Baltic Sea Diet Score (BSDS) based on the Pyramid is associated with a decreased risk of obesity and abdominal obesity. The population-based cross-sectional study included 4720 Finns (25-74 years) from the National FINRISK 2007 study. Diet was assessed using a validated FFQ. The score included Nordic fruits and berries, vegetables, cereals, ratio of PUFA:SFA and trans-fatty acids, low-fat milk, fish, red and processed meat, total fat (percentage of energy), and alcohol. Height, weight and waist circumference (WC) were measured and BMI values were calculated. In a multivariable model, men in the highest v. lowest BSDS quintile were more likely to have normal WC (OR 0·48, 95 % CI 0·29, 0·80). In women, this association was similar but not significant (OR 0·65, 95 % CI 0·39, 1·09). The association appeared to be stronger in younger age groups (men: OR 0·23, 95 % CI 0·08, 0·62; women: OR 0·17, 95 % CI 0·05, 0·58) compared with older age groups. Nordic cereals and alcohol were found to be the most important BSDS components related to WC. No association was observed between the BSDS and BMI. The present study suggests that combination of Nordic foods, especially cereals and moderate alcohol consumption, is likely to be inversely associated with abdominal obesity.
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Affiliation(s)
- Noora Kanerva
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, PO Box 30, FI-00270 Helsinki, Finland
| | - Niina E Kaartinen
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, PO Box 30, FI-00270 Helsinki, Finland
| | - Ursula Schwab
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, 70211 Kuopio, Finland
| | | | - Satu Männistö
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, PO Box 30, FI-00270 Helsinki, Finland
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Duntas L, Micic D. Adiposopathy and thyroid disease: tracing the pathway to cardiovascular risk. Expert Rev Cardiovasc Ther 2013; 10:797-803. [PMID: 22894634 DOI: 10.1586/erc.12.47] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Adiposopathy, defined as functionally disturbed adipose tissue mainly composed of large adipocytes and induced by chronic excess of food intake, has been associated with immune, metabolic and endocrine derangements promoting inflammation and, eventually, cardiovascular disease. Adiposopathy may positively influence thyrotropin-stimulating hormone, by raising leptin levels, and triggering autoimmunity. In this regard, it is hypothesized that the increased thyrotropin-stimulating hormone is independent of the negative regulation of the thyroid hormone, thereby constituting a secondary phenomenon and not a causal effect. Replacement therapy with thyroid hormones should therefore be applied following strict individualized consideration. Leptin is involved in the immune response and neuroendocrine appetite regulation, while leptin resistance may further promote autoimmune disease. The lipid derangement in adiposopathy may be aggravated in the presence of hypothyroidism and thus considerably augment cardiovascular risk. Lifestyle-modification counselling, including low-fat dietary intake and regular physical exercise, is today the cornerstone of adiposopathy treatment. Meanwhile, new drug formulations, such as leptin and leptin analogs, 5-HT2C-receptor agonist, and potent thyromimetics, currently comprise a promising armamentarium against adiposity and adiposopathy.
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Affiliation(s)
- Leonidas Duntas
- Endocrine Unit, Evgenidion Hospital, University of Athens Medical School, Athens, Greece.
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Canale MP, Manca di Villahermosa S, Martino G, Rovella V, Noce A, De Lorenzo A, Di Daniele N. Obesity-related metabolic syndrome: mechanisms of sympathetic overactivity. Int J Endocrinol 2013; 2013:865965. [PMID: 24288531 PMCID: PMC3833340 DOI: 10.1155/2013/865965] [Citation(s) in RCA: 140] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 09/10/2013] [Indexed: 12/15/2022] Open
Abstract
The prevalence of the metabolic syndrome has increased worldwide over the past few years. Sympathetic nervous system overactivity is a key mechanism leading to hypertension in patients with the metabolic syndrome. Sympathetic activation can be triggered by reflex mechanisms as arterial baroreceptor impairment, by metabolic factors as insulin resistance, and by dysregulated adipokine production and secretion from visceral fat with a mainly permissive role of leptin and antagonist role of adiponectin. Chronic sympathetic nervous system overactivity contributes to a further decline of insulin sensitivity and creates a vicious circle that may contribute to the development of hypertension and of the metabolic syndrome and favor cardiovascular and kidney disease. Selective renal denervation is an emerging area of interest in the clinical management of obesity-related hypertension. This review focuses on current understanding of some mechanisms through which sympathetic overactivity may be interlaced to the metabolic syndrome, with particular regard to the role of insulin resistance and of some adipokines.
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Affiliation(s)
- Maria Paola Canale
- Division of Hypertension and Nephrology, Department of System Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Simone Manca di Villahermosa
- Division of Hypertension and Nephrology, Department of System Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Giuliana Martino
- Division of Hypertension and Nephrology, Department of System Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Valentina Rovella
- Division of Hypertension and Nephrology, Department of System Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Annalisa Noce
- Division of Hypertension and Nephrology, Department of System Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Antonino De Lorenzo
- Division of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Nicola Di Daniele
- Division of Hypertension and Nephrology, Department of System Medicine, University of Rome Tor Vergata, Rome, Italy
- *Nicola Di Daniele:
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Nguyen B, Tao M, Yu P, Mauro C, Seidman MA, Wang YE, Mitchell J, Ozaki CK. Preoperative diet impacts the adipose tissue response to surgical trauma. Surgery 2012; 153:584-93. [PMID: 23274098 DOI: 10.1016/j.surg.2012.11.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2012] [Accepted: 11/01/2012] [Indexed: 01/24/2023]
Abstract
BACKGROUND Short-term changes in preoperative nutrition can have profound effects on surgery-related outcomes such as ischemia/reperfusion injury in preclinical models. Dietary interventions that lend protection against stress in animal models (eg, fasting, dietary restriction [DR]) impact adipose tissue quality/quantity. Adipose tissue holds high surgical relevance because of its anatomic location and large tissue volume, and it is ubiquitously traumatized during surgery. Yet the response of adipose tissue to trauma under clinically relevant circumstances including dietary status remains poorly defined. We hypothesized that preoperative diet alters the adipose tissue response to surgical trauma. METHODS A novel mouse model of adipose tissue surgical trauma was employed. Dietary conditions (diet-induced obesity [DIO], preoperative DR) were modulated before application of surgical adipose tissue trauma in the context of clinically common scenarios (different ages, simulated bacterial wound contamination). Local/distant adipose tissue phenotypic responses were measured as represented by gene expression of inflammatory, tissue remodeling/growth, and metabolic markers. RESULTS Surgical trauma had a profound effect on adipose tissue phenotype at the site of trauma. Milder but significant distal effects on non-traumatized adipose tissue were also observed. DIO exacerbated the inflammatory aspects of this response, and preoperative DR tended to reverse these changes. Age and lipopolysaccharide (LPS)-simulated bacterial contamination also impacted the adipose tissue response to trauma, with young adult animals and LPS treatment exacerbating the proinflammatory response. CONCLUSION Surgical trauma dramatically impacts both local and distal adipose tissue biology. Short-term preoperative DR may offer a strategy to attenuate this response.
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Affiliation(s)
- Binh Nguyen
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Chandalia M, Davila H, Pan W, Szuszkiewicz M, Tuvdendorj D, Livingston EH, Abate N. Adipose tissue dysfunction in humans: a potential role for the transmembrane protein ENPP1. J Clin Endocrinol Metab 2012; 97:4663-72. [PMID: 23012391 PMCID: PMC3513530 DOI: 10.1210/jc.2012-2018] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
CONTEXT Adipose tissue (AT) helps to regulate body fat partitioning and systemic lipid/glucose metabolism. We have recently reported lipid/glucose metabolism abnormalities and increased liver triglyceride content in an AT-selective transgenic model overexpressing ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), the AdiposeENPP1-Tg mouse. OBJECTIVE The aim of the study was to test the translational hypothesis that AT-ENPP1 overexpression associates with AT dysfunction (changes in AT gene expression, plasma fatty acid, and adipokine levels), increased liver triglyceride deposition, and systemic insulin resistance in humans. DESIGN/SETTING/PARTICIPANTS A total of 134 young normoglycemic men and women were subjected to body composition studies, hyperinsulinemic-euglycemic clamps, and AT needle biopsy. Twenty men also had liver/muscle nuclear magnetic resonance spectroscopy. MAIN OUTCOME MEASURES Predetermined measures included AT expression of ENPP1 and other lipid metabolism/inflammation genes, plasma adipokines, and nonesterified fatty acid (NEFA) levels, liver/muscle triglyceride content, and the systemic glucose disposal rate. RESULTS After statistical adjustment for body fat content, increasing AT-ENPP1 was associated with up-regulation of genes involved in NEFA metabolism and inflammation, increased postabsorptive NEFA levels, decreased plasma adiponectin, increased liver triglyceride content, and systemic insulin resistance in men. In women, there were no changes in plasma adiponectin, NEFAs, or glucose disposal rate associated with increasing AT-ENPP1, despite increased expression of lipid metabolism and inflammation genes in AT. CONCLUSIONS Increased AT-ENPP1 is associated with AT dysfunction, increased liver triglyceride deposition, and systemic insulin resistance in young normoglycemic men. These findings are concordant with the AdiposeENPP1-Tg phenotype and identify a potential target of therapy for health complications of AT dysfunction, including type 2 diabetes and cardiovascular disease.
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Affiliation(s)
- Manisha Chandalia
- Department of Medicine, Division of Endocrinology, University of Texas Medical Branch at Galveston, Texas 77555-1060, USA
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Abstract
To describe the link between adipocytes and cardiometabolic risk and present mechanisms by which obesity contributes to dysglycemia, dyslipidemia, hypertension, and a prothrombotic, inflammatory state favoring atherogenesis. Review of relevant literature compiled via a literature search (PUBMED) of English-language literature publications between 1994 and 2010. Cardiometabolic risk is a term that includes a series of conditions and factors, which contribute to increased risk of developing atherosclerosis. Cardiometabolic risk encompasses traditional coronary risks factors such as smoking, arterial hypertension, diabetes, obesity, elevated cholesterol, old age, male gender, and a positive family history of early coronary events plus additional contributing factors such as insulin resistance, atherogenic dyslipidemia, physical inactivity, unhealthy eating, inflammation, and hypercoagulable state. Adipocyte accumulation and dysfunction contribute to most, if not all, of the cardiometabolic risk factors. A number of different pathologic mechanisms through which adipocytes contribute to cardiometabolic risk and promote atherosclerosis are reviewed. Dysfunctional adipocytes are associated with the development of insulin resistance, hyperglycemia, atherogenic dyslipidemia and arterial hypertension, and favor a prothrombotic and proinflammatory state. Adipocytes dysfunction increases cardiometabolic risk through a variety of mechanisms.
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Impact of uremia on human adipose tissue phenotype. J Surg Res 2012; 179:175-82. [PMID: 23058473 DOI: 10.1016/j.jss.2012.08.043] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Revised: 08/16/2012] [Accepted: 08/22/2012] [Indexed: 12/25/2022]
Abstract
BACKGROUND Recognition of adipose-related signaling in surgery is increasing, although direct interrogation of human adipose has been sparse. Few scenarios rival uremia for health impact. We hypothesized that adipose from uremic patients holds a relatively higher adipose-derived hormone and proinflammatory adipokine signature; we simultaneously evaluated the impact of clinical parameters on adipose phenotype. MATERIALS AND METHODS Adipose was harvested from surgical patients. Histology and protein analyses were completed for select mediators. RESULTS In the overall cohort of 71 patients, the mean age was 63.4 y; 46.4% of patients had diabetes mellitus, 49.2% had hyperlipidemia, and 53.5% had coronary artery disease. Compared with nonuremic patients, uremic patients had one-tenth of the levels of leptin (P < 0.001), one-third of the levels of adiponectin (P < 0.001), and threefold higher levels of resistin (P < 0.001). Females had sixfold higher levels of leptin, 1.5-fold higher levels of adiponectin, and twofold higher levels of tumor necrosis factor alpha but equivalent resistin. There were differences in mediators when stratified by age. In both the obese and nonobese strata, we observed a concordant pattern of association (magnitude or significance) of uremia and leptin, adiponectin, and resistin. No differentials in other mediators emerged on body mass index stratification. Multiple regression analysis for leptin, adiponectin, and resistin (with age, gender, and uremia as independent variables) showed uremia as the highest independent predictor of all the three mediators. CONCLUSIONS Advanced chronic kidney disease is associated with perturbations in adipose-derived hormones (leptin, adiponectin, and resistin). Adipose adiponectin and leptin (in contrast to reported plasma levels) were lower in uremic patients; there is an inverse correlation between adipose resistin and renal function. Compared with other clinical parameters including body mass index, uremia dominates overall in determining adipose phenotype, highlighting the complex biological interplay between uremia and adipose biology.
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Abstract
An estimated 72.5 million American adults are obese, and the growing US obesity epidemic is responsible for substantial increase in morbidity and mortality, as well as increased health care costs. Obesity results from a combination of personal and societal factors, but is often viewed as a character flaw rather than a medical condition. This leads to stigma and discrimination towards obese individuals and decreases the likelihood of effective intervention. Conditions related to obesity are increasingly common, such as metabolic syndrome, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), all of which indicate high risk for type 2 diabetes (T2DM). This paper reviews the progression from obesity to diabetes, identifying physiological changes that occur along this path as well as opportunities for patient identification and disease prevention. Patients with prediabetes (defined as having IFG, IGT or both) and/or metabolic syndrome require interventions designed to preserve insulin sensitivity and β-cell function, both of which start to deteriorate prior to T2DM diagnosis. Lifestyle modification, including both healthy eating choices and increased physical activity, is essential for weight management and diabetes prevention. Although sustained weight loss is often considered by patients and physicians as being impossible to achieve, effective interventions do exist. Specifically, the Diabetes Prevention Program (DPP) and programs modelled along its parameters have shown repeated successes, even with long-term maintenance. Recent setbacks in the development of medications for weight loss further stress the importance of lifestyle management. By viewing obesity as a metabolic disorder rather than a personal weakness, we can work with patients to address this increasingly prevalent condition and improve long-term health outcomes.
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Affiliation(s)
- A J Garber
- Departments of Medicine, Biochemistry and Molecular Biology, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
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Reduced cardiovascular risk following bariatric surgeries is related to a partial recovery from "adiposopathy". Obes Surg 2012; 21:1928-36. [PMID: 21625910 DOI: 10.1007/s11695-011-0447-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND Altered cytokine secretion from dysfunctional adipose tissue or "adiposopathy" is implicated in obesity related inflammation and may mediate reduced cardiovascular disease (CVD) risk in response to weight loss after bariatric surgery. We hypothesized that bariatric surgery reduces CVD risk by favorably altering the pro-inflammatory profile of adipose tissue as a result of weight loss. METHODS In this observational study with repeated measures, 142 patients underwent bariatric surgery of which 45 returned for follow-up at ∼6 months. At both time-points, lipid profiles and levels of plasma adiponectin, leptin, and TNF-α were obtained. Ratios of various adipokine parameters were related to pre- and post- surgical (gastric bypass vs. other restrictive bariatric procedures) lipid ratios. RESULTS Prior to surgery, circulating adiponectin and the adiponectin/TNF-α ratio was strongly associated with CVD risk characterized by levels of triglycerides, HDL, and the TC/HDL, LDL/HDL, and TG/HDL ratios (all P < 0.05). Following bariatric surgery, BMI was decreased by 22%, adiponectin was increased by 93%, and leptin decreased by 50% as compared to baseline (all P < 0.01). TNF-α levels increased by 120% (P < 0.01) following surgery. Post-surgical changes in adiponectin and the leptin/adiponectin ratio were strongly associated with incremental improvements in triglycerides, HDL, and TC/HDL, LDL/HDL and TG/HDL ratios (all P < 0.05). Roux-en-y gastric bypass surgery (RYGB) as compared to other bariatric procedures was associated with more robust improvements in BMI, HDL, and leptin/adiponectin ratio than other gastric restrictive procedures (P < 0.05). CONCLUSIONS Thus, bariatric surgery, especially RYGB, ameliorates CVD risk through a partial recovery from "adiposopathy", distinctively characterized by improved adiponectin and the leptin/adiponectin ratio.
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Rogers C, Moukdar F, McGee MA, Davis B, Buehrer BM, Daniel KW, Collins S, Barakat H, Robidoux J. EGF receptor (ERBB1) abundance in adipose tissue is reduced in insulin-resistant and type 2 diabetic women. J Clin Endocrinol Metab 2012; 97:E329-40. [PMID: 22238402 DOI: 10.1210/jc.2011-1033] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
CONTEXT Indications of adipose tissue dysfunction correlate with systemic insulin resistance and type 2 diabetes. It has been suggested that a defect in adipose tissue turnover may be involved in the development of these disorders. Whether this dysfunction causes or exacerbates systemic insulin resistance is not fully understood. OBJECTIVES, PARTICIPANTS, AND MEASURES: We tested whether the expression of members of the mitogenic ErbB family was reduced in adipose tissue of insulin-resistant individuals and whether ErbB1 and ErbB2 were involved in adipogenesis. Thirty-two women covering a wide range of body mass index values and insulin sensitivity participated in the cross-sectional portion of this study. We also studied preadipocytes isolated from 12 insulin-sensitive individuals to evaluate the impact of ErbB1 or ErbB2 inhibition on adipogenesis in vitro. For this purpose, we measured phospho-ErbB1 and phospho-ErbB2 levels using ELISA and the expression of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ-regulated genes by real-time PCR. RESULTS Among the ErbB family members, only ErbB1 expression was correlated with insulin sensitivity. Additionally, ErbB1 levels correlated positively with PPARγ and several PPARγ-regulated genes including acyl-coenzyme A synthetase long-chain family member 1 (ACSL1), adiponectin, adipose tissue triacylglycerol lipase (ATGL), diacylglycerol acyl transferase 1 (DGAT1), glycerol-3-phosphate dehydrogenase 1 (GPD1), and lipoprotein lipase (LPL), but negatively with CD36 and fatty acid-binding protein 4 (FABP4). In preadipocyte culture, ErbB1, but not ErbB2, inhibition was associated with a reduction in the expression of all the above-mentioned genes. CONCLUSIONS These findings demonstrate a key role for ErbB1 in adipogenesis and suggest that lower ErbB1 protein abundance may lead to adipose tissue dysfunction.
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Affiliation(s)
- Carlyle Rogers
- Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA
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Abate N. Adipocyte maturation arrest: a determinant of systemic insulin resistance to glucose disposal. J Clin Endocrinol Metab 2012; 97:760-3. [PMID: 22392952 PMCID: PMC3319217 DOI: 10.1210/jc.2012-1140] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Mittendorfer B. Origins of metabolic complications in obesity: adipose tissue and free fatty acid trafficking. Curr Opin Clin Nutr Metab Care 2011; 14:535-41. [PMID: 21849896 PMCID: PMC3711689 DOI: 10.1097/mco.0b013e32834ad8b6] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW Obesity is associated with a number of serious medical complications that are risk factors for cardiovascular disease (e.g., insulin resistance, dyslipidemia, and liver fat accumulation). Alterations in fatty acid trafficking, both between tissues and within cells, represent a key feature in the pathophysiology of the metabolic complications in obese patients. The ways by which fatty acid 're-routing' may affect metabolic function are summarized in this article. RECENT FINDINGS Ectopic fat accumulation (i.e., fat accumulation in nonadipose tissues) appears to be a key feature distinguishing metabolically healthy from metabolically abnormal patients. This observation has led to the belief that an imbalance in fatty acid trafficking away from adipose tissue toward nonadipose tissues is a primary cause for the development of metabolic alterations in obese patients. More recently, however, it has become apparent that fatty acid trafficking within nonadipose tissues cells (i.e., toward storage - in the form of triglycerides - and oxidation) may be equally important in determining a person's risk for development of metabolic disease. SUMMARY The pathophysiology of the metabolic alterations associated with obesity is probably multifactorial within a complex network of coordinated physiological responses. Only through the integration of multiple concepts, will it be possible to further our understanding in this area and to help prevent the metabolic alterations associated with obesity.
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Affiliation(s)
- Bettina Mittendorfer
- Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
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Levy S, Gomes FR, Sterodimas A. Macroscopic anatomic changes of subcutaneous fat tissue in massive-weight-loss patients. Aesthetic Plast Surg 2011; 35:814-9. [PMID: 21461626 DOI: 10.1007/s00266-011-9701-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2011] [Accepted: 03/01/2011] [Indexed: 11/30/2022]
Abstract
BACKGROUND After massive weight loss (MWL), patients are known to experience significant improvement in obesity-associated comorbid conditions and metabolic disturbances, but almost two-thirds of them require reconstructive body-contouring surgery. METHODS The authors present an anatomic study of surgical pieces obtained from 28 patients (17 women and 11 men) during torsoplasty and abdominoplasty procedures performed in their department from January 2007 to January 2008. The patients ranged in age from 39 to 52 years (mean, 43.3 years). The patients were divided into three groups. Group A consisted of 9 patients who had a normal body mass index (BMI) and stable weight (±5 kg) over the preceding 3 years. Group B consisted of 10 patients who had followed a nutritional diet over the preceding 3 years, achieving a mean weight loss of 42.2 kg (range, 38-52 kg). Group C consisted of 9 patients who had undergone bariatric surgery and insertion of a gastric band before 2004, achieving a mean weight loss of 47 kg (range, 40-57 kg). The authors evaluated the anatomy of the subcutaneous tissue in four body areas: the epigastric, umbilical, hypogastric, and lumbar regions. RESULTS The macroscopic anatomic results of the subcutaneous tissue in the three groups are presented. The patients who underwent bariatric surgery (group C) had significant alterations of the subcutaneous tissue anatomy in all four body areas studied. Plastic surgeons who perform composite body-contouring procedures for this group of patients, combining truncal liposuction and lipoabdominoplasty procedures, should be aware of these anatomic changes. The possibility of a cannula perforating an internal organ during liposuction may have been higher for the group C patients than for the group A and group B patients. CONCLUSION Knowledge concerning the anatomy of the subcutaneous fat in post-MWL patients allows a better choice of contouring procedure from an anatomic point of view, performance of a more rational and effective procedure, and differentiation of the technique depending on the area of the body, avoiding major complications.
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Affiliation(s)
- Sergio Levy
- Hospital Municipal Barata Ribeiro, 1450 Rio de Janeiro, Brazil
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