|
1
|
Xu F, Zhang C. Obesity and 1-year all-cause survival of adult intensive care patients with heart failure: data from the MIMIC-IV. Diabetol Metab Syndr 2024; 16:190. [PMID: 39113062 PMCID: PMC11304645 DOI: 10.1186/s13098-024-01428-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 07/24/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Heart failure is a disease that threatens global public safety. In recent years, the obesity paradox has been studied in cardiovascular disease and other fields. With the progress of aging, metabolic changes and regulation of fat function, it also provides many bridges for the dialogue between disease and molecular metabolism. The purpose of this study is to investigate the effect of obesity on the outcome of adult intensive care patients with heart failure combined with age factors. METHOD Data were derived from the fourth-generation Medical Information Marketplace for Intensive Care (MIMIC-IV version2.1) using structured query language on the Navicat (12.0.11) platform. People were divided into two groups based on the body mass index (BMI), one group with BMI ≥ 30 kg/m² and another group with BMI < 30 kg/m². Afterwards, the patients were divided into two subgroups based on their ages. One group included patients aged<60, and the other included patients aged ≥ 60. The extracted information includes demographic characteristics, laboratory findings, comorbidities, scores. Main results included in-hospital mortality, ICU mortality, and 1-year mortality. Secondary outcomes included hospital interval and ICU interval, use of renal replacement therapy, and rates of noninvasive and invasive ventilation support. RESULT In this cohort study, 3390 people were in the BMI<30 group, 2301 people were in the BMI ≥ 30 group, 960 people were in the age<60 group, and 4731 people were in the age ≥ 60 group, including 3557 patients after propensity score matching in high age group. Among patients aged ≥ 60, BMI ≥ 30 group vs. BMI<30 group showed significantly lower in-hospital mortality (13% vs. 16%) and one-year mortality (41% vs. 55%), respectively. Neither primary nor secondary outcomes were significantly described in the competition among patients aged under 60. Restricted cubic spline reveals a J-shaped nonlinear association between BMI and clinical endpoints within the entire cohort. Kaplan-Meier curves revealed a survival advantage in BMI ≥ 30 group (p < 0.001). Following age stratification, a beneficial effect of BMI categories on one-year mortality risk was observed in heart failure patients aged ≥ 60 (Univariable HR, 0.71, 95% CI, 0.65-0.78, p < 0.001; Multivariable HR, 0.74, 95% CI, 0.67-0.81, p < 0.001), but not in those under 60 years old. OUTCOME In ICU patients with heart failure, obesity offers a survival benefit to those aged ≥ 60. No obesity paradox was observed in patients younger than 60 years old. The obesity paradox applies to patients aged ≥ 60 with heart failure.
Collapse
Affiliation(s)
- Fei Xu
- Department of Anesthesiology, School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, 610091, China
| | - Cheng Zhang
- Department of Anesthesiology, School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, 610091, China.
- Department of Anesthesiology, Cheng Du Xin Jin District Maternal and Child Health Care Hospital, Chengdu, China.
| |
Collapse
|
|
2
|
Yoshiko A, Ohta M, Kuramochi R, Mitsuyama H. Serum Adiponectin and Leptin Is Not Related to Skeletal Muscle Morphology and Function in Young Women. J Endocr Soc 2023; 7:bvad032. [PMID: 36911319 PMCID: PMC9998031 DOI: 10.1210/jendso/bvad032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Indexed: 03/03/2023] Open
Abstract
Adipokines secreted from adipose tissue, such as adiponectin and leptin, enhance skeletal muscle metabolism. Animal studies have shown that adipokine knockout leads to a reduction in muscle function. Muscle function is determined by muscle size and quality; therefore, it is speculated that lower adipokine levels affect skeletal muscle size and quality, eventually leading to lower muscle function. This study aimed to investigate the relationship between adipokines and skeletal muscle morphology and function in young individuals. A total of 21 young women participated in this study. Adiponectin and leptin levels were analyzed using fasting blood samples from all participants. B-mode ultrasound images of the thigh and calf were obtained, and the muscle thickness and echo intensity were measured in the vastus lateralis (VL) and medial gastrocnemius (MG). The shear modulus was measured from the VL and MG using shear wave elastography. Knee extension and plantar flexion peak torques were measured as muscle functions. Adiponectin and leptin were not related to echo intensity, shear modulus, and muscle thickness in the VL and MG (rs = -0.26-0.37, P > .05). Furthermore, no relationship was observed between adiponectin, leptin, knee extension, and dorsiflexion peak torque (rs = -0.28-0.41, P > .05). These negative results suggest that adiponectin and leptin levels in young women are not associated with muscle size and quality, nor are they related to muscle function.
Collapse
Affiliation(s)
- Akito Yoshiko
- Faculty of Liberal Arts and Sciences, Chukyo University, Toyota 470-0393, Japan
| | - Megumi Ohta
- Faculty of Liberal Arts and Sciences, Chukyo University, Toyota 470-0393, Japan
| | - Rieko Kuramochi
- School of Health and Sport Sciences, Chukyo University, Toyota 470-0393, Japan
| | - Hirohito Mitsuyama
- School of Health and Sport Sciences, Chukyo University, Toyota 470-0393, Japan
| |
Collapse
|
|
3
|
Liu N, Chen X, Ran J, Yin J, Zhang L, Yang Y, Cen J, Dai H, Zhou J, Gao K, Zhang J, Liu L, Chen Z, Wang H. Investigating the change in gene expression profile of blood mononuclear cells post-laparoscopic sleeve gastrectomy in Chinese obese patients. Front Endocrinol (Lausanne) 2023; 14:1049484. [PMID: 36998473 PMCID: PMC10043499 DOI: 10.3389/fendo.2023.1049484] [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: 10/12/2022] [Accepted: 02/27/2023] [Indexed: 03/15/2023] Open
Abstract
BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is a sustainable technique that effectively treats morbid obesity. However, the molecular mechanisms underlying the improvement of metabolic health following this process warrants more investigation. This study investigates LSG-related molecules and uses bulk RNA-sequencing high-throughput analysis to unravel their regulatory mechanisms. METHODS Peripheral blood mononuclear cells (PBMC) were collected from ten obese patients with BMI ≥ 32.5 kg/m2 in the Department of General Surgery of Kunming First People's Hospital. After LSG, patients were followed up for one month, and blood samples were retaken. Blood samples from ten patients before and after LSG and bulk RNA-Seq data were analyzed in this study. LSG-associated gene expression was detected by weighted gene coexpression network analysis (WGCNA) and differential analysis. Subsequently, essential signature genes were identified using logistic least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were utilized to reveal the potential functions of the target genes. Furthermore, the Pearson correlation of signature genes with leptin and lipocalin was also explored. Finally, we constructed a robust endogenous RNA (ceRNA) network based on miRWalk and starBase databases. RESULTS We identified 18 overlapping genes from 91 hub genes, and 165 differentially expressed mRNAs (DE-mRNA), which were revealed to be significantly associated with immune cells, immune response, inflammatory response, lipid storage, and localization upon functional enrichment analysis. Three signature genes, IRF1, NFKBIA, and YRDC, were identified from the 18 overlapping genes by LASSO and SVM-REF algorithms. The logistic regression model based on the three signature genes highlighted how robustly they discriminated between samples. ssGSEA indicated these genes to be involved in lipid metabolism and degradation pathways. Moreover, leptin levels were significantly reduced in patients undergoing LSG, and NFKBIA significantly negatively correlated with leptin. Finally, we identified how the long non-coding RNA (lncRNA) ATP2B1-AS1 regulated the expression of the signature genes by competitively binding to six microRNAs (miRNAs), which were hsa-miR-6509-5p, hsa-miR-330-5P, hsa-miR-154-5P, hsa-miR-145-5P, hsa-miR4726-5P and hsa-miR-134-5P. CONCLUSION This study identified three critical regulatory genes significantly differentiated between patients before and after LSG treatment and highlighted their potentially crucial role after bariatric surgery. This provides novel insights to increase our understanding of the underlying mechanisms of weight loss and associated metabolic improvement after bariatric surgery.
Collapse
Affiliation(s)
- Na Liu
- Department of Endocrinology, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Xiaolei Chen
- Department of Endocrinology, The First People’s Hospital of Kunming, Kunming, Yunnan, China
- *Correspondence: Xiaolei Chen,
| | - Jianghua Ran
- Department of Endocrinology, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Jianhui Yin
- Department of General Surgery, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Lijun Zhang
- Department of General Surgery, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Yuelin Yang
- Clinical Laboratory, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Jianchang Cen
- Department of Vascular Surgery, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Hongmei Dai
- Ophthalmology, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Jiali Zhou
- Department of Endocrinology, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Kui Gao
- Department of Endocrinology, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Jihong Zhang
- Department of General Surgery, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Liyin Liu
- Department of General Surgery, The First People’s Hospital of Kunming, Kunming, Yunnan, China
| | - Zhiyuan Chen
- Faculty of Physical Education, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Haibin Wang
- Department of Infectious Diseases, The Affiliated Hospital of YunNan University, Kunming, Yunnan, China
| |
Collapse
|
|
4
|
Delaney KZ, Santosa S. Sex differences in regional adipose tissue depots pose different threats for the development of Type 2 diabetes in males and females. Obes Rev 2022; 23:e13393. [PMID: 34985183 DOI: 10.1111/obr.13393] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 10/26/2021] [Accepted: 10/28/2021] [Indexed: 01/08/2023]
Abstract
Type 2 diabetes mellitus (T2DM) affects males and females disproportionately. In midlife, more males have T2DM than females. The sex difference in T2DM prevalence is, in part, explained by differences in regional adipose tissue characteristics. With obesity, changes to regional adipokine and cytokine release increases the risk of T2DM in both males and females with males having greater levels of TNFα and females having greater levels of leptin, CRP, and adiponectin. Regional immune cell infiltration appears to be pathogenic in both sexes via different routes as males with obesity have greater VAT ATM and a decrease in the protective Treg cells, whereas females have greater SAT ATM and T cells. Lastly, the ability of female adipose tissue to expand all regions through hyperplasia, rather than hypertrophy, protects them against the development of large insulin-resistant adipocytes that dominate male adipose tissue. The objective of this review is to discuss how sex may affect regional differences in adipose tissue characteristics and how these differences may distinguish the development of T2DM in males and females. In doing so, we will show that the origins of T2DM development differ between males and females.
Collapse
Affiliation(s)
- Kerri Z Delaney
- Department of Health, Kinesiology and Applied Physiology, Concordia University, Montréal, Québec, Canada.,Metabolism, Obesity and Nutrition Lab, PERFORM Centre, Concordia University, Montréal, Québec, Canada.,Centre de recherche - Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada
| | - Sylvia Santosa
- Department of Health, Kinesiology and Applied Physiology, Concordia University, Montréal, Québec, Canada.,Metabolism, Obesity and Nutrition Lab, PERFORM Centre, Concordia University, Montréal, Québec, Canada.,Centre de recherche - Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada
| |
Collapse
|
|
5
|
Yoshiko A, Maeda H, Takahashi H, Koike T, Tanaka N, Akima H. Contribution of skeletal muscle and serum lipids to muscle contraction induced by neuromuscular electrical stimulation in older individuals. Physiol Rep 2022; 10:e15236. [PMID: 35312173 PMCID: PMC8935638 DOI: 10.14814/phy2.15236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 02/19/2022] [Accepted: 03/03/2022] [Indexed: 11/24/2022] Open
Abstract
Intramyocellular lipids (IMCL) stored in droplets in muscle cells and free fatty acids (FFA) from fat cells in the blood are the main substrates of adenosine triphosphate during continuous muscle contractions of relatively lower intensity. Although it is known that the lipid oxidative capacity decreases with aging, the effect of IMCL and FFA on muscle contraction in older individuals remains unclear. The purpose of this study was to investigate the contribution of skeletal muscle lipids and blood lipids as energy sources for muscle contraction in older individuals. Eighteen older individuals (mean age: 70.4 ± 3.5 years) underwent muscle contraction intervention induced by intermittent neuromuscular electrical stimulation (NMES) to the vastus lateralis for 30 min. Fasting blood samples were obtained and proton magnetic resonance spectroscopy (1 H-MRS) was performed before and after NMES, and the parameters (including IMCL and extramyocellular lipid [EMCL]) from 1 H-MRS, along with FFA and adiponectin levels, were analyzed using the blood samples of all participants. Levels of IMCL and EMCL did not change (p > 0.05); however, FFA and adiponectin levels decreased from 1.1 ± 0.5 mEq/L to 0.8 ± 0.2 mEq/L and 12.0 ± 5.3 μg/ml to 11.4 ± 5.0 μg/ml, after NMES (p < 0.05), respectively. These findings indicate that serum lipids, but not skeletal muscle lipids, are the energy substrate utilized during involuntary muscle contraction in older individuals.
Collapse
Affiliation(s)
- Akito Yoshiko
- Faculty of Liberal Arts and SciencesChukyo UniversityToyotaAichiJapan
| | - Hisashi Maeda
- Graduate School of MedicineNagoya UniversityNagoyaAichiJapan
| | - Hideyuki Takahashi
- Faculty of Health and Sport SciencesUniversity of TsukubaTsukubaIbarakiJapan
| | - Teruhiko Koike
- Graduate School of MedicineNagoya UniversityNagoyaAichiJapan
- Research Center of Health, Physical Fitness & SportsNagoya UniversityNagoyaAichiJapan
| | - Noriko Tanaka
- Research Center of Health, Physical Fitness & SportsNagoya UniversityNagoyaAichiJapan
- Graduate School of Education and Human DevelopmentNagoya UniversityNagoyaAichiJapan
| | - Hiroshi Akima
- Research Center of Health, Physical Fitness & SportsNagoya UniversityNagoyaAichiJapan
- Graduate School of Education and Human DevelopmentNagoya UniversityNagoyaAichiJapan
| |
Collapse
|
|
6
|
FTO and PLAG1 Genes Expression and FTO Methylation Predict Changes in Circulating Levels of Adipokines and Gastrointestinal Peptides in Children. Nutrients 2021; 13:nu13103585. [PMID: 34684585 PMCID: PMC8538237 DOI: 10.3390/nu13103585] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/03/2021] [Accepted: 10/06/2021] [Indexed: 12/19/2022] Open
Abstract
Adipokines and gastrointestinal tract hormones are important metabolic parameters, and both epigenetic factors and differential gene expression patterns may be associated with the alterations in their concentrations in children. The function of the FTO gene (FTO alpha-ketoglutarate dependent dioxygenase) in the regulation of the global metabolic rate is well described, whereas the influence of protooncogene PLAG1 (PLAG1 zinc finger) is still not fully understood. A cross-sectional study on a group of 26 children with various BMI values (15.3–41.7; median 28) was carried out. The aim was to evaluate the dependencies between the level of methylation and expression of aforementioned genes with the concentration of selected gastrointestinal tract hormones and adipokines in children. Expression and methylation were measured in peripheral blood mononuclear DNA by a microarray technique and a restriction enzyme method, respectively. All peptide concentrations were determined using the enzyme immunoassay method. The expression level of both FTO and PLAG1 genes was statistically significantly related to the concentration of adipokines: negatively for apelin and leptin receptor, and positively for leptin. Furthermore, both FTO methylation and expression negatively correlated with the concentration of resistin and visfatin. Cholecystokinin was negatively correlated, whereas fibroblast growth factor 21 positively correlated with methylation and expression of the FTO gene, while FTO and PLAG1 expression was negatively associated with the level of cholecystokinin and glucagon-like peptide-1. The PLAG1 gene expression predicts an increase in leptin and decrease in ghrelin levels. Our results indicate that the FTO gene correlates with the concentration of hormones produced by the adipose tissue and gastrointestinal tract, and PLAG1 gene may be involved in adiposity pathogenesis. However, the exact molecular mechanisms still need to be clarified.
Collapse
|
|
7
|
Ramon-Krauel M, Leal-Witt MJ, Osorio-Conles Ó, Amat-Bou M, Lerin C, Selva DM. Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity. Mol Cell Pediatr 2021; 8:3. [PMID: 33689083 PMCID: PMC7947057 DOI: 10.1186/s40348-021-00113-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/01/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Sex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels and lower adiponectin levels. Moreover, we have recently elucidated the molecular mechanisms by which TNFα and adiponectin regulate hepatic SHBG production. AIM The main objective of this study was to assess if the adult associations between TNFα, adiponectin, and SHBG are present in prepubertal children. METHODS We determined several morphometric and biochemical parameters in normal-weight (n=15) and obese prepubertal (n=51) children, as well as quantified plasma SHBG, TNFα receptor 1 (TNFα-R1), and adiponectin levels. RESULTS Our results showed that prepubertal children with obesity had decreased plasma SHBG levels compared to normal-weight controls (67 nmol/L vs 172 nmol/L). Importantly, SHBG plasma levels correlated significantly (P < 0.05) with TNFα (negatively, ßstd= - 0.31) and adiponectin (positively, ßstd= 0.58) suggesting an important role of these two cytokines in determining plasma SHBG levels in prepubertal children. CONCLUSIONS Our results suggest that plasma adiponectin levels may play a more important role than TNFα in influencing plasma SHBG levels in our prepubertal population with obesity.
Collapse
Affiliation(s)
- Marta Ramon-Krauel
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - María Jesús Leal-Witt
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - Óscar Osorio-Conles
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - Montse Amat-Bou
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - Carles Lerin
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain.
| | - David M Selva
- Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Pg Vall d'Hebron 119-129, 08035, Barcelona, Spain.
| |
Collapse
|
|
8
|
Castorani V, Polidori N, Giannini C, Blasetti A, Chiarelli F. Insulin resistance and type 2 diabetes in children. Ann Pediatr Endocrinol Metab 2020; 25:217-226. [PMID: 33401880 PMCID: PMC7788344 DOI: 10.6065/apem.2040090.045] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 06/05/2020] [Indexed: 12/27/2022] Open
Abstract
Type 2 diabetes (T2D) is an emerging health risk in obese children and adolescents. Both environmental (lack of physical activity, excess nutritional intake, sedentary lifestyle) and genetic factors contribute to this global epidemic. The growing prevalence of T2D in youth is also associated with a consistently increased incidence of metabolic and cardiovascular complications. Insulin resistance (IR), i.e., whole-body decreased glucose uptake in response to physiological insulin levels, determines impaired glucose homeostasis and it is recognized as cardinal trigger of T2D and cardiovascular disease in both adults and children. In particular, IR and beta-cell dysfunction lead to the persistent hyperglycemia which characterizes T2D. Indeed, both pathological states influence each other and presumably play a crucial, synergistic role in the pathogenesis of T2D, although the precise mechanisms are not completely understood. However, beta-cell dysfunction and IR induce impaired glucose metabolism, thus leading to the progression to T2D. Therefore, understanding the mechanisms correlated with the decline of beta-cell function and IR is crucial in order to control, prevent, and treat T2D in youth. This review focuses on the current knowledge regarding IR and T2D in children and adolescents and showcases interesting opportunities and stimulating challenges for the development of new preventative approaches and therapeutic strategies for young patients with T2D.
Collapse
Affiliation(s)
| | - Nella Polidori
- Department of Pediatrics, University of Chieti, Chieti, Italy
| | - Cosimo Giannini
- Department of Pediatrics, University of Chieti, Chieti, Italy
| | | | - Francesco Chiarelli
- Department of Pediatrics, University of Chieti, Chieti, Italy,Address for correspondence: Francesco Chiarelli, MD, PhD Department of Pediatrics, University of Chieti, Via dei Vestini, 5, I-66100 Chieti, Italy Tel: +39-0871-358015 Fax: +39-0871-574538 E-mail:
| |
Collapse
|
|
9
|
Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:6425782. [PMID: 32566092 DOI: 10.1155/2020/6425782] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 04/12/2020] [Accepted: 04/17/2020] [Indexed: 12/30/2022]
Abstract
Hypertension induces vascular hypertrophy, which changes blood vessels structurally and functionally, leading to reduced tissue perfusion and further hypertension. It is also associated with dysregulated levels of the circulating adipokines leptin and adiponectin (APN). Leptin is an obesity-associated hormone that promotes vascular smooth muscle cell (VSMC) hypertrophy. APN is a cardioprotective hormone that has been shown to attenuate hypertrophic cardiomyopathy. In this study, we investigated the molecular mechanisms of hypertension-induced VSMC remodeling and the involvement of leptin and APN in this process. To mimic hypertension, the rat portal vein (RPV) was mechanically stretched, and the protective effects of APN on mechanical stretch-induced vascular remodeling and the molecular mechanisms involved were examined by using 10 μg/ml APN. Mechanically stretching the RPV significantly decreased APN protein expression after 24 hours and APN mRNA expression in a time-dependent manner in VSMCs. The mRNA expression of the APN receptors AdipoR1, AdipoR2, and T-cadherin significantly increased after 15 hours of stretch. The ratio of APN/leptin expression in VSMCs significantly decreased after 24 hours of mechanical stretch. Stretching the RPV for 3 days increased the weight and [3H]-leucine incorporation significantly, whereas APN significantly reduced hypertrophy in mechanically stretched vessels. Stretching the RPV for 10 minutes significantly decreased phosphorylation of LKB1, AMPK, and eNOS, while APN significantly increased p-LKB1, p-AMPK, and p-eNOS in stretched vessels. Mechanical stretch significantly increased p-ERK1/2 after 10 minutes, whereas APN significantly reduced stretch-induced ERK1/2 phosphorylation. Stretching the RPV also significantly increased ROS generation after 1 hour, whereas APN significantly decreased mechanical stretch-induced ROS production. Exogenous leptin (3.1 nM) markedly increased GATA-4 nuclear translocation in VSMCs, whereas APN significantly attenuated leptin-induced GATA-4 nuclear translocation. Our results decipher molecular mechanisms of APN-induced attenuation of mechanical stretch-mediated vascular hypertrophy, with the promising potential of ultimately translating this protective hormone into the clinic.
Collapse
|
|
10
|
Adolescent Obesity: Diet Quality, Psychosocial Health, and Cardiometabolic Risk Factors. Nutrients 2019; 12:nu12010043. [PMID: 31877943 PMCID: PMC7020092 DOI: 10.3390/nu12010043] [Citation(s) in RCA: 145] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 12/13/2019] [Accepted: 12/19/2019] [Indexed: 01/03/2023] Open
Abstract
Obesity is a multifaceted chronic condition with several contributing causes, including biological risk factors, socioeconomic status, health literacy, and numerous environmental influences. Of particular concern are the increasing rates of obesity in children and adolescents, as rates of obesity in youth in the United States have tripled within the last three decades. Youth from historically disadvantaged backgrounds tend to have higher rates of obesity compared to other groups. Adolescents often do not meet intake recommendations for certain food groups and nutrients, which may contribute to a heightened risk of obesity. With obesity disproportionately affecting adolescents (ages 12–19 years), negative effects of excess adiposity may be particularly salient during this critical period of development. The presentation of chronic cardiometabolic disease symptoms typically observed in adults, such as hypertension, hyperglycemia, dyslipidemia, and inflammation, are becoming increasingly common in adolescents with obesity. Additionally, there is dynamic interplay between obesity and psychosocial health, as adolescents with obesity may have increased levels of stress, depressive symptoms, and reduced resilience. To reduce and prevent adolescent obesity, the implementation of theory-driven multicomponent school- and community-based interventions have been suggested. These interventions promote knowledge and self-efficacy for healthful practices that have the potential to progress to sustained behavior change.
Collapse
|
|
11
|
da Silva CDC, Zambon MP, Vasques ACJ, Camilo DF, De Bernardi Rodrigues AM, Antonio MÂRDGM, Dâmaso AR, Tufik S, de Mello MT, Campos RMDS, Geloneze B, for the Brazilian Metabolic Syndrome Study (BRAMS) Investigators. Homeostatic model assessment of adiponectin (HOMA-Adiponectin) as a surrogate measure of insulin resistance in adolescents: Comparison with the hyperglycaemic clamp and homeostatic model assessment of insulin resistance. PLoS One 2019; 14:e0214081. [PMID: 30908521 PMCID: PMC6433366 DOI: 10.1371/journal.pone.0214081] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Accepted: 03/06/2019] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated. OBJECTIVES To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance. METHODS This was a cross-sectional study of 56 adolescents (aged 10-18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis. RESULTS In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 (P = 0.02) for HOMA-Adiponectin and 0.859 (P < 0.0001) HOMA-IR. CONCLUSIONS The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy.
Collapse
Affiliation(s)
- Cleliani de Cassia da Silva
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Sciences, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- * E-mail:
| | - Mariana Porto Zambon
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Sciences, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- Department of Pediatrics, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
| | - Ana Carolina Junqueira Vasques
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Sciences, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- School of Applied Sciences, University of Campinas - Unicamp, Limeira, São Paulo, Brazil
| | - Daniella Fernandes Camilo
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Sciences, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
| | - Ana Maria De Bernardi Rodrigues
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- School of Health and Life Sciences, University Center Our Lady of Patronage, Itu, São Paulo, Brazil
| | - Maria Ângela Reis de Góes Monteiro Antonio
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Sciences, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- Department of Pediatrics, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
| | - Ana Raimunda Dâmaso
- Postgraduate Program of Nutrition, Federal University of São Paulo - Unifesp, São Paulo, São Paulo, Brazil
| | - Sergio Tufik
- Department of Psychobiology, Federal University of São Paulo - Unifesp, São Paulo, São Paulo, Brazil
| | - Marco Tulio de Mello
- Department of Psychobiology, Federal University of São Paulo - Unifesp, São Paulo, São Paulo, Brazil
- School of Physical Education, Physiotherapy and Occupational Therapy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Raquel Munhoz da Silveira Campos
- Department of Physiotherapy, Therapeutic Resources Laboratory, Federal University of São Carlos - UFSCar, São Carlos, São Paulo, Brazil
| | - Bruno Geloneze
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Sciences, University of Campinas - Unicamp, Campinas, São Paulo, Brazil
| | | |
Collapse
|
|
12
|
van Meijel RL, Blaak EE, Goossens GH. Adipose tissue metabolism and inflammation in obesity. MECHANISMS AND MANIFESTATIONS OF OBESITY IN LUNG DISEASE 2019:1-22. [DOI: 10.1016/b978-0-12-813553-2.00001-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
13
|
Babenko AY, Savitskaya DA, Kononova YA, Trofimova AY, Simanenkova AV, Vasilyeva EY, Shlyakhto EV. Predictors of Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes and Obesity. J Diabetes Res 2019; 2019:1365162. [PMID: 30944827 PMCID: PMC6421820 DOI: 10.1155/2019/1365162] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 12/03/2018] [Accepted: 12/19/2018] [Indexed: 01/16/2023] Open
Abstract
RATIONALE It is well known that diabetes mellitus (DM) exacerbates the mechanisms underlying atherosclerosis. Currently, glucagon-like peptide-1 receptor agonists (aGLP-1) have one of the most prominent cardioprotective effects among the antidiabetic agents. However, the treatment with aGLP-1 is effective only in 50-70% of the cases. Taking into account the high cost of these medications, discovery of the predictors of optimal response to treatment is required. PURPOSE To identify the predictors of the greater impact of aGLP-1 on HbA1c levels, weight reduction, and improvement in lipid profile. METHODS The study group consisted of 40 patients with type 2 DM (T2DM) and obesity who were treated with aGLP-1. The follow-up period was 24 weeks. Patients' evaluation was conducted at baseline and after 24 weeks. In addition, it included the assessment of the hormones involved in glucose and lipid metabolism and appetite regulation. RESULTS Patients who have initially higher BMI (body mass index), glycemia, and triglycerides (TG) had better improvement in these parameters undergoing aGLP-1 treatment. In patients with a BMI loss ≥ 5%, GLP-1 and fasting ghrelin levels were higher and ghrelin level in postnutritional status was lower. The HbA1c levels decreased more intensively in participants with higher GLP-1 levels. TG responders had lower baseline fasting glucose-dependent insulinotropic peptide (GIP) and postprandial ghrelin levels. CONCLUSION The evaluation of the glycemic control, lipid profile, and GLP-1, GIP, and ghrelin levels are useable for estimating the expected efficacy of aGLP-1.
Collapse
Affiliation(s)
- Alina Yu. Babenko
- Almazov National Medical Research Centre, 2 Akkuratova Street, St. Petersburg, 197341, Russia
| | - Daria A. Savitskaya
- Almazov National Medical Research Centre, 2 Akkuratova Street, St. Petersburg, 197341, Russia
| | - Yulia A. Kononova
- Almazov National Medical Research Centre, 2 Akkuratova Street, St. Petersburg, 197341, Russia
| | | | - Anna V. Simanenkova
- Almazov National Medical Research Centre, 2 Akkuratova Street, St. Petersburg, 197341, Russia
| | - Elena Yu. Vasilyeva
- Almazov National Medical Research Centre, 2 Akkuratova Street, St. Petersburg, 197341, Russia
| | - Evgeny V. Shlyakhto
- Almazov National Medical Research Centre, 2 Akkuratova Street, St. Petersburg, 197341, Russia
| |
Collapse
|
|
14
|
Muscle quality characteristics of muscles in the thigh, upper arm and lower back in elderly men and women. Eur J Appl Physiol 2018; 118:1385-1395. [DOI: 10.1007/s00421-018-3870-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 04/17/2018] [Indexed: 12/14/2022]
|
|
15
|
Foucan L, Larifla L, Durand E, Rambhojan C, Armand C, Michel CT, Billy R, Dhennin V, De Graeve F, Rabearivelo I, Sand O, Lacorte JM, Froguel P, Bonnefond A. High Prevalence of Rare Monogenic Forms of Obesity in Obese Guadeloupean Afro-Caribbean Children. J Clin Endocrinol Metab 2018; 103:539-545. [PMID: 29216354 DOI: 10.1210/jc.2017-01956] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 11/30/2017] [Indexed: 11/19/2022]
Abstract
CONTEXT The population of Guadeloupe Island exhibits a high prevalence of obesity. OBJECTIVE We aimed to investigate whether rare genetic mutations in genes involved in monogenic obesity (or diabetes) might be causal in this population of Afro-Caribbean ancestry. DESIGN AND SETTING This was a secondary analysis of a study on obesity conducted in schoolchildren from Guadeloupe in 2013 that aimed to assess changes in children's profiles after a lifestyle intervention program. Through next-generation sequencing, we sequenced coding regions of 59 genes involved in monogenic obesity or diabetes in participants from this study. PARTICIPANTS AND INTERVENTIONS A total of 25 obese schoolchildren from Guadeloupe were screened for rare mutations (nonsynonymous, splice-site, or insertion/deletion) in 59 genes. MAIN OUTCOME MEASURES Correlation between phenotypes and mutations of interest. RESULTS We detected five rare heterozygous mutations in five different children with obesity: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations that were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations that were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutations in ABCC8 (p.Lys1521Asn and p.Ala625Val) or KCNJ11 (p.Val13Met and p.Val151Met) that were of uncertain significance. CONCLUSIONS We were able to detect pathogenic or likely pathogenic mutations linked to severe obesity in >15% of this population, which is much higher than what we observed in Europeans (∼5%).
Collapse
Affiliation(s)
- Lydia Foucan
- Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France
- Department of Public Health, University Hospital, Pointe-à-Pitre, Guadeloupe, France
| | - Laurent Larifla
- Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France
- Cardiology Unit, University Hospital, Pointe-à-Pitre, Guadeloupe, France
| | - Emmanuelle Durand
- CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France
| | - Christine Rambhojan
- Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France
| | - Christophe Armand
- Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France
- Department of Public Health, University Hospital, Pointe-à-Pitre, Guadeloupe, France
| | - Carl-Thony Michel
- Cardiology Unit, University Hospital, Pointe-à-Pitre, Guadeloupe, France
| | - Rachel Billy
- Cardiology Unit, University Hospital, Pointe-à-Pitre, Guadeloupe, France
| | - Véronique Dhennin
- CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France
| | - Franck De Graeve
- CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France
| | - Iandry Rabearivelo
- CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France
| | - Olivier Sand
- CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France
| | - Jean-Marc Lacorte
- Department of Endocrine and Oncological Biochemistry, University Hospitals of Pitié-Salpétrière‒Charles Foix, Paris, France
- Inserm, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, Paris, France
| | - Philippe Froguel
- CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France
- Department of Genomics of Common Disease, Imperial College London, London, United Kingdom
| | - Amélie Bonnefond
- CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France
- Department of Genomics of Common Disease, Imperial College London, London, United Kingdom
| |
Collapse
|
|
16
|
Zabarsky G, Beek C, Hagman E, Pierpont B, Caprio S, Weiss R. Impact of Severe Obesity on Cardiovascular Risk Factors in Youth. J Pediatr 2018; 192:105-114. [PMID: 29246331 PMCID: PMC9338402 DOI: 10.1016/j.jpeds.2017.09.066] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Revised: 09/02/2017] [Accepted: 09/22/2017] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To compare cardiovascular risk factor clustering (CVRFC) in severely obese youth with those with lower degrees of obesity. STUDY DESIGN We divided a childhood obesity clinic derived cohort into the degrees of obesity (class I, II, and III) and added a "class IV" category corresponding to >160% of the 95th centile of body mass index (BMI) for age and sex. In a cross-sectional analysis, we investigated the presence of CVRFC in 2244 participants; in 621 who were followed longitudinally, we investigated the determinants of endpoint CVRFC. RESULTS Class IV obesity was associated with increased risk for CVRFC compared with overweight (OR = 17.26, P < .001) at a similar magnitude to class III obesity (OR = 17.26, P < .001). Male children were at greater risk for presence of CVRFC (OR = 1.57, P = .03) compared with female children. Adiponectin (OR = 0.90, P < .001) and leptin levels (OR = 0.98, P = .008) were protective, independent of degree of obesity. Baseline class IV obesity was associated with increased risk compared with overweight of having CVRFC at follow-up (OR = 5.76, P = .001), to a similar extent as class III obesity (OR = 5.36, P = .001). Changes in the degree of obesity were significant predictors of CVRFC on follow-up (OR = 1.04, P < .01 per percent BMI change). CONCLUSIONS The metabolic risk associated with obesity in childhood is conferred prior to reaching class IV obesity. An individualized risk stratification approach in children with severe obesity should be based on presence of complications rather than simple BMI cutoffs. TRIAL REGISTRATION ClinicalTrials.gov NCT01967849.
Collapse
Affiliation(s)
- Gali Zabarsky
- Department of Human Metabolism and Nutrition, Braun School of Public Health, Hebrew University, Jerusalem, Israel
| | - Cherise Beek
- Department of Human Metabolism and Nutrition, Braun School of Public Health, Hebrew University, Jerusalem, Israel
| | - Emilia Hagman
- Department of Human Metabolism and Nutrition, Braun School of Public Health, Hebrew University, Jerusalem, Israel
| | | | - Sonia Caprio
- Department of Pediatrics, Yale University, New-Haven, CT, USA
| | - Ram Weiss
- Department of Human Metabolism and Nutrition, Braun School of Public Health, Hebrew University, Jerusalem, Israel.
| |
Collapse
|
|
17
|
Ighbariya A, Weiss R. Insulin Resistance, Prediabetes, Metabolic Syndrome: What Should Every Pediatrician Know? J Clin Res Pediatr Endocrinol 2017; 9:49-57. [PMID: 29280741 PMCID: PMC5790325 DOI: 10.4274/jcrpe.2017.s005] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The Metabolic syndrome describes a clustering of typical cardiovascular risk factors. The syndrome is also known as "Insulin Resistance syndrome" as a substantial part of the pathophysiology is driven by resistance to the metabolic effects of insulin. The major cause of insulin resistance in childhood is a typical lipid partitioning pattern characterized by increased deposition of lipids within insulin responsive tissues, such as the liver and skeletal muscle and within the viscera. This lipid deposition pattern is also associated with infiltration of intra-abdominal tissues with cells of the immune system, inducing systemic, low-grade inflammation typically observed in insulin resistant obese children and adolescents. Several clues derived from a careful history and physical examination, along with a basic laboratory workup, provide clues in regards to risk stratification in obese children.
Collapse
Affiliation(s)
- Ahmad Ighbariya
- Ruth Rappaport Children’s Hospital, Clinic of Pediatrics, Haifa, Israel
,* Address for Correspondence: Ruth Rappaport Children’s Hospital, Clinic of Pediatrics, Haifa, Israel E-mail:
| | - Ram Weiss
- Ruth Rappaport Children’s Hospital, Clinic of Pediatrics, Haifa, Israel
| |
Collapse
|
|
18
|
Caffeoylquinic Acid-Rich Extract of Aster glehni F. Schmidt Ameliorates Nonalcoholic Fatty Liver through the Regulation of PPAR δ and Adiponectin in ApoE KO Mice. PPAR Res 2017; 2017:3912567. [PMID: 29201040 PMCID: PMC5672637 DOI: 10.1155/2017/3912567] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 06/04/2017] [Accepted: 09/10/2017] [Indexed: 12/13/2022] Open
Abstract
Aster glehni is well known for its therapeutic properties. This study was performed to investigate the effects of A. glehni on nonalcoholic fatty liver disease (NAFLD) in atherosclerotic condition, by determining the levels of biomarkers related to lipid metabolism and inflammation in serum, liver, and adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride level decreased in all groups treated with A. glehni. Serum adiponectin concentration and protein levels of peroxisome proliferator-activated receptor δ, 5′ adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, superoxide dismutase, and PPARγ coactivator 1-alpha in liver tissues increased in the groups treated with A. glehni. Conversely, protein levels of ATP citrate lyase, fatty acid synthase, tumor necrosis factor α, and 3-hydroxy-3-methylglutaryl-CoA reductase and the concentrations of interleukin 6 and reactive oxygen species decreased upon A. glehni. Triglyceride concentration in the liver was lower in mice treated with A. glehni than in control mice. Lipid accumulation in HepG2 and 3T3-L1 cells decreased upon A. glehni treatment; this effect was suppressed in the presence of the PPARδ antagonist, GSK0660. Our findings suggest that A. glehni extracts may ameliorate NAFLD through regulation of PPARδ, adiponectin, and the related subgenes.
Collapse
|
|
19
|
Abstract
Obesity has been estimated to decrease life expectancy by as little as 0.8 to as much as 7 years being the second leading cause of preventable death in the United States after smoking. Along with the increase in the prevalence of obesity, there has been a dramatic rise of the prevalence of prediabetes and type 2 diabetes among adolescents. Despite that, very little is known about the pathogenesis of these conditions in pediatrics and about how we could detect prediabetes in an early stage in order to prevent full blown diabetes. In this review we summarize the current knowledge on the pathophysiology of prediabetes and type 2 diabetes in adolescents and describe how biomarkers of beta-cell function might help identifying those individuals who are prone to progress from normal glucose tolerance towards prediabetes and overt type 2 diabetes. To better understand and fight this disease, we will need to explore and develop novel therapeutic strategies and individuate more sensitive and specific biomarkers that can allow an earlier detection of the disease.
Collapse
|
|
20
|
Cord blood and child plasma adiponectin levels in relation to childhood obesity risk and fat distribution up to 5 y. Pediatr Res 2017; 81:745-751. [PMID: 28052063 DOI: 10.1038/pr.2016.275] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Accepted: 10/30/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND Few human studies have explored the role of adiponectin in early life on growth and adipose tissue development. METHODS High molecular weight (HMW) and total adiponectin levels from 141 cord blood samples and plasma blood samples from 40 3-y-old children were analyzed. Associations between adiponectin levels in cord blood and child plasma, and infant/child growth and fat mass measurements up to the age of 5 y were assessed using linear regression models. RESULTS HMW cord blood adiponectin was positively associated with weight, BMI percentiles, and lean body mass at birth only. At 3 and 4 y, positive associations were found with cord blood adiponectin and sum of four skinfold thickness measures and percentage of body fat following adjustment for maternal and child covariates, but did not persist at 5 y. There was no significant evidence of an association between child plasma HMW adiponectin and growth or body composition characteristics at 3-5 y. CONCLUSION Our results do not support the hypothesis that HMW cord blood adiponectin is a useful biomarker for the prediction of adiposity at the age of 5 y. Additionally, there is no evidence that plasma HMW adiponectin levels predict body fat distribution between 3-5 y.
Collapse
|
|
21
|
Wang A, Li T, An P, Yan W, Zheng H, Wang B, Mu Y. Exendin-4 Upregulates Adiponectin Level in Adipocytes via Sirt1/Foxo-1 Signaling Pathway. PLoS One 2017; 12:e0169469. [PMID: 28122026 PMCID: PMC5266308 DOI: 10.1371/journal.pone.0169469] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Accepted: 12/17/2016] [Indexed: 12/22/2022] Open
Abstract
Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases.
Collapse
Affiliation(s)
- Anping Wang
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
| | - Ting Li
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
| | - Ping An
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
| | - Wenhua Yan
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
| | - Hua Zheng
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
| | - Baoan Wang
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
| | - Yiming Mu
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
- * E-mail:
| |
Collapse
|
|
22
|
Nissen A, Fonvig CE, Chabanova E, Bøjsøe C, Trier C, Pedersen O, Hansen T, Thomsen HS, Holm JC. 1H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity. Obes Sci Pract 2016; 2:376-384. [PMID: 28090342 PMCID: PMC5192542 DOI: 10.1002/osp4.61] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 07/01/2016] [Accepted: 07/02/2016] [Indexed: 12/16/2022] Open
Abstract
Background The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between MetS and ectopic fat may offer clinical relevance. Objectives To investigate the prevalence of MetS, or components hereof, and ectopic fat accumulation in liver and skeletal muscle tissue in children, as well as interactions between these. Methods Two‐hundred‐and‐sixteen children and adolescents (95 boys) with overweight/obesity were investigated, as well as 47 controls (22 boys) with normal weight. The assessments included anthropometry, fasting blood biochemistry and blood pressure measurements. Liver and muscle lipid contents were assessed by proton magnetic resonance spectroscopy. Results We observed an odds ratio in girls with overweight/obesity of 12.2 (95% confidence interval: [3.8; 49.0]) for exhibiting MetS when hepatic steatosis was present, whereas no association was observed in boys with overweight/obesity (odds ratio 0.7 [0.2; 2.7]). The odds ratio of exhibiting MetS in the presence of muscular steatosis was 3.5 [1.4; 9.5] in girls with overweight/obesity and 1.0 [0.2; 5.6] in boys with overweight/obesity. Similar results were seen for girls with overweight/obesity exhibiting concurrent hepatic and muscular steatoses. Conclusion Hepatic and muscular steatoses were associated with MetS among girls, but not among boys with overweight/obesity.
Collapse
Affiliation(s)
- A Nissen
- The Children's Obesity Clinic, Department of Pediatrics Copenhagen University Hospital Holbæk Holbæk Denmark
| | - C E Fonvig
- The Children's Obesity Clinic, Department of Pediatrics Copenhagen University Hospital Holbæk Holbæk Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences University of @Copenhagen Copenhagen Ø Denmark
| | - E Chabanova
- Department of Diagnostic Radiology Copenhagen University Hospital Herlev Herlev Denmark
| | - C Bøjsøe
- The Children's Obesity Clinic, Department of Pediatrics Copenhagen University Hospital Holbæk Holbæk Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences University of @Copenhagen Copenhagen Ø Denmark
| | - C Trier
- The Children's Obesity Clinic, Department of Pediatrics Copenhagen University Hospital Holbæk Holbæk Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences University of @Copenhagen Copenhagen Ø Denmark
| | - O Pedersen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences University of @Copenhagen Copenhagen Ø Denmark
| | - T Hansen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences University of @Copenhagen Copenhagen Ø Denmark
| | - H S Thomsen
- Department of Diagnostic Radiology Copenhagen University Hospital Herlev Herlev Denmark; Faculty of Health and Medical Sciences University of Copenhagen Copenhagen N Denmark
| | - J-C Holm
- The Children's Obesity Clinic, Department of Pediatrics Copenhagen University Hospital Holbæk Holbæk Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences University of @Copenhagen Copenhagen Ø Denmark; Faculty of Health and Medical Sciences University of Copenhagen Copenhagen N Denmark
| |
Collapse
|
|
23
|
Circulating Interferon-Gamma Levels Are Associated with Low Body Weight in Newly Diagnosed Kenyan Non-Substance Using Tuberculosis Individuals. Interdiscip Perspect Infect Dis 2016; 2016:9415364. [PMID: 26880909 PMCID: PMC4736369 DOI: 10.1155/2016/9415364] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Revised: 12/03/2015] [Accepted: 12/08/2015] [Indexed: 02/07/2023] Open
Abstract
Although interferon-gamma, interleukin-10, and adiponectin are key immunopathogenesis mediators of tuberculosis, their association with clinical manifestations of early stage disease is inconclusive. We determined interferon-gamma, interleukin-10, and adiponectin levels in clinically and phenotypically well-characterised non-substance using new pulmonary tuberculosis patients (n = 13) and controls (n = 14) from Kenya. Interferon-gamma levels (P < 0.0001) and interferon-gamma to interleukin-10 (P < 0.001) and interferon-gamma to adiponectin (P = 0.027) ratios were elevated in tuberculosis cases. Correlation analyses in tuberculosis cases showed associations of interferon-gamma levels with body weight (ρ = -0.849; P < 0.0001), body mass index (ρ = 0.664; P = 0.013), hip girth (ρ = -0.579; P = 0.038), and plateletcrit (ρ = 0.605; P = 0.028); interferon-gamma to interleukin-10 ratio with diastolic pressure (ρ = -0.729; P = 0.005); and interferon-gamma to adiponectin ratio with body weight (ρ = -0.560; P = 0.047), body mass index (ρ = -0.604; P = 0.029), and plateletcrit (ρ = 0.793; P = 0.001). Taken together, our results suggest mild-inflammation in early stage infection characterised by upregulation of circulating interferon-gamma production in newly infected TB patients.
Collapse
|
|
24
|
Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A. Differential Role of Leptin and Adiponectin in Cardiovascular System. Int J Endocrinol 2015; 2015:534320. [PMID: 26064110 PMCID: PMC4433709 DOI: 10.1155/2015/534320] [Citation(s) in RCA: 135] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Accepted: 04/23/2015] [Indexed: 02/07/2023] Open
Abstract
Leptin and adiponectin are differentially expressed adipokines in obesity and cardiovascular diseases. Leptin levels are directly associated with adipose tissue mass, while adiponectin levels are downregulated in obesity. Although significantly produced by adipocytes, leptin is also produced by vascular smooth muscle cells and cardiomyocytes. Plasma leptin concentrations are elevated in cases of cardiovascular diseases, such as hypertension, congestive heart failure, and myocardial infarction. As for the event of left ventricular hypertrophy, researchers have been stirring controversy about the role of leptin in this form of cardiac remodeling. In this review, we discuss how leptin has been shown to play an antihypertrophic role in the development of left ventricular hypertrophy through in vitro experiments, population-based cross-sectional studies, and longitudinal cohort studies. Conversely, we also examine how leptin may actually promote left ventricular hypertrophy using in vitro analysis and human-based univariate and multiple linear stepwise regression analysis. On the other hand, as opposed to leptin's generally detrimental effects on the cardiovascular system, adiponectin is a cardioprotective hormone that reduces left ventricular and vascular hypertrophy, oxidative stress, and inflammation. In this review, we also highlight adiponectin signaling and its protective actions on the cardiovascular system.
Collapse
Affiliation(s)
- C. M. Ghantous
- Department of Anatomy, Cell biology and Physiology, American University of Beirut, DTS-255, P.O. Box 11-0236, Beirut 1107-2020, Lebanon
| | - Z. Azrak
- Department of Pharmacology and Toxicology, American University of Beirut, DTS-255, P.O. Box 11-0236, Beirut 1107-2020, Lebanon
| | - S. Hanache
- Department of Anatomy, Cell biology and Physiology, American University of Beirut, DTS-255, P.O. Box 11-0236, Beirut 1107-2020, Lebanon
| | - W. Abou-Kheir
- Department of Anatomy, Cell biology and Physiology, American University of Beirut, DTS-255, P.O. Box 11-0236, Beirut 1107-2020, Lebanon
| | - A. Zeidan
- Department of Anatomy, Cell biology and Physiology, American University of Beirut, DTS-255, P.O. Box 11-0236, Beirut 1107-2020, Lebanon
- *A. Zeidan:
| |
Collapse
|
|
25
|
Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol 2014; 13:103. [PMID: 24957699 PMCID: PMC4230016 DOI: 10.1186/1475-2840-13-103] [Citation(s) in RCA: 165] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Accepted: 05/26/2014] [Indexed: 01/14/2023] Open
Abstract
Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance and inflammation. Central obesity accompanied by insulin resistance is a key factor in the development of metabolic syndrome (MS) and future macrovascular complications. Moreover, the remarkable correlation between coronary artery disease (CAD) and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes mellitus (T2DM) may share a common biological background. We summarize here the current knowledge about the influence of adiponectin on insulin sensitivity and endothelial function, discussing its forthcoming prospects and potential role as a therapeutic target for MS, T2DM, and cardiovascular disease. Adiponectin is present in the circulation as a dimer, trimer or protein complex of high molecular weight hexamers, >400 kDa. AdipoR1 and AdipoR2 are its major receptors in vivo mediating the metabolic actions. Adiponectin stimulates phosphorylation and AMP (adenosin mono phosphate) kinase activation, exerting direct effects on vascular endothelium, diminishing the inflammatory response to mechanical injury and enhancing endothelium protection in cases of apolipoprotein E deficiency. Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis, CAD, T2DM. Lifestyle correction helps to favorably modify plasma adiponectin levels. Low adiponectinemia in obese patients is raised via continued weight loss programs in both diabetic and nondiabetic individuals and is also accompanied by reductions in pro-inflammatory factors. Diet modifications, like intake of fish, omega-3 supplementation, adherence to a Mediterranean dietary pattern and coffee consumption also increase adiponectin levels. Antidiabetic and cardiovascular pharmacological agents, like glitazones, glimepiride, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are also able to improve adiponectin concentration. Fibric acid derivatives, like bezafibrate and fenofibrate, have been reported to enhance adiponectin levels as well. T-cadherin, a membrane-associated adiponectin-binding protein lacking intracellular domain seems to be a main mediator of the antiatherogenic adiponectin actions. The finding of novel pharmacologic agents proficient to improve adiponectin plasma levels should be target of exhaustive research. Interesting future approaches could be the development of adiponectin-targeted drugs chemically designed to induce the activaton of its receptors and/or postreceptor signaling pathways, or the development of specific adiponectin agonists.
Collapse
Affiliation(s)
- Enrique Z Fisman
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
| | | |
Collapse
|
|
26
|
Development of a murine model of early sepsis in diet-induced obesity. BIOMED RESEARCH INTERNATIONAL 2014; 2014:719853. [PMID: 24967393 PMCID: PMC4054609 DOI: 10.1155/2014/719853] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Accepted: 02/25/2014] [Indexed: 12/15/2022]
Abstract
Sepsis, a global health issue, is the most common cause of mortality in the intensive care unit. The aim of this study was to develop a new model of sepsis that investigates the impact of prolonged western diet (WD) induced obesity on the response to early sepsis. Male C57BL/6 mice were fed either a high fat WD or normal chow diet (NCD) for 6, 15, or 27 weeks. Septic obese mice at 15 and 27 weeks had significantly lower levels of lung myeloperoxidase (26.3 ± 3.80 U/mg tissue) compared to age matched ad lib (44.1 ± 2.86 U/mg tissue) and diet restricted (63.2 ± 5.60 U/mg tissue) controls. Low levels of lung inflammation were not associated with changes in hepatic cytokines and oxidative stress levels. Obese mice had significantly (P < 0.0001) larger livers compared to controls. Histological examination of the livers demonstrated that WD fed mice had increased inflammation with pronounced fat infiltration, steatosis, and hepatocyte ballooning. Using this model of prolonged exposure to high fat diet we have data that agree with recent clinical observations suggesting obese individuals are protected from sepsis-induced lung injury. This model will allow us to investigate the links between damage to the hepatic microcirculation, immune response, and lung injury.
Collapse
|
|
27
|
Sakurai Y, Tamura Y, Takeno K, Kumashiro N, Sato F, Kakehi S, Ikeda S, Ogura Y, Saga N, Naito H, Katamoto S, Fujitani Y, Hirose T, Kawamori R, Watada H. Determinants of intramyocellular lipid accumulation after dietary fat loading in non-obese men. J Diabetes Investig 2014; 2:310-7. [PMID: 24843504 PMCID: PMC4014973 DOI: 10.1111/j.2040-1124.2010.00091.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Aims/Introduction: Accumulation of intramyocellular lipid (IMCL) is associated with insulin resistance. However, the factors affecting the change in IMCL remain to be elucidated. The aim of the present study was to determine the factors that influence the change in IMCL level after high‐fat loading. Materials and Methods: The study subjects were 37 non‐obese men. Each subject consumed a high‐fat diet for 3 days after a normal‐fat diet for 3 days. After each diet program, IMCL levels in the tibialis anterior (TA‐IMCL) and soleus (SOL‐IMCL) were measured by proton magnetic resonance spectroscopy. Glucose infusion rate (GIR) was evaluated by euglycemic hyperinsulinemic clamp as an index of peripheral insulin sensitivity. Results: The high‐fat diet significantly increased TA‐IMCL and SOL‐IMCL by ∼30 and ∼20%, respectively (P < 0.05), whereas it did not significantly alter GIR. The increase in SOL‐IMCL, but not in TA‐IMCL, negatively correlated with serum high molecular weight (HMW)‐adiponectin (r = −0.36, P < 0.05) and HMW‐/total‐adiponectin ratio (r = −0.46, P < 0.05). Although high‐fat diet‐related changes in SOL‐IMCL showed high inter‐individual variations, in subjects doing exercise, changes in SOL‐IMCL (r = 0.55, P < 0.05) and TA‐IMCL (r = 0.61, P < 0.05) positively correlated with daily physical activity level. In contrast, in sedentary subjects, changes in SOL‐IMCL (r = −0.50, P < 0.01) and TA‐IMCL (r = −0.48, P < 0.05) negatively correlated with daily physical activity. Conclusions: HMW‐adiponectin and daily physical activity are determinants of IMCL accumulation by a high‐fat diet. Intriguingly, the effect of daily physical activity on the change in IMCL depends on the level of regular exercise. (J Diabetes Invest,doi: 10.1111/j.2040‐1124.2010.00091.x, 2011)
Collapse
Affiliation(s)
- Yuko Sakurai
- Department of Medicine, Metabolism and Endocrinology
| | - Yoshifumi Tamura
- Department of Medicine, Metabolism and Endocrinology ; Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo
| | | | | | - Fumihiko Sato
- Department of Medicine, Metabolism and Endocrinology
| | - Saori Kakehi
- Department of Medicine, Metabolism and Endocrinology ; Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo
| | - Shinichi Ikeda
- Department of Medicine, Metabolism and Endocrinology ; Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo
| | - Yuji Ogura
- Institute of Health and Sports Science and Medicine ; Department of Exercise Physiology, Graduate School of Health and Sports Science, Juntendo University, Chiba
| | - Norio Saga
- Institute of Health and Sports Science and Medicine ; Department of Exercise Physiology, Graduate School of Health and Sports Science, Juntendo University, Chiba
| | - Hisashi Naito
- Institute of Health and Sports Science and Medicine ; Department of Exercise Physiology, Graduate School of Health and Sports Science, Juntendo University, Chiba
| | - Shizuo Katamoto
- Institute of Health and Sports Science and Medicine ; Department of Exercise Physiology, Graduate School of Health and Sports Science, Juntendo University, Chiba
| | | | | | - Ryuzo Kawamori
- Department of Medicine, Metabolism and Endocrinology ; Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo ; Center for Therapeutic Innovations in Diabetes ; Center for Beta Cell Biology and Regeneration, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Hirotaka Watada
- Department of Medicine, Metabolism and Endocrinology ; Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo
| |
Collapse
|
|
28
|
Yee JK, Mao CS, Ross MG, Paul Lee WN, Desai M, Toda A, Kjos SL, Hicks RA, Patterson ME. High oleic/stearic fatty-acid desaturation index in cord plasma from infants of mothers with gestational diabetes. J Perinatol 2014; 34:357-63. [PMID: 24577432 PMCID: PMC4022182 DOI: 10.1038/jp.2014.23] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2013] [Revised: 11/25/2013] [Accepted: 01/06/2014] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Enhanced fatty-acid desaturation by stearoyl-CoA desaturase enzyme-1 (SCD1) is associated with obesity. This study determined desaturation in the cord plasma of newborns of mothers with and without gestational diabetes (GDM). STUDY DESIGN Newborns of mothers with GDM (n=21) and without (control, n=22) were recruited. Cord plasma fatty-acid desaturation indices (palmitoleic/palmitic, oleic/stearic ratios) were compared, and correlated with anthropometrics and biochemical measures. A subset of very low-density lipoprotein (VLDL) desaturation indices were determined to approximate the liver SCD1 activity. RESULT The total oleic/stearic index was higher in GDM, despite adjustment for cord glucose concentrations. Among GDM and controls, the oleic/stearic index correlated with cord glucose concentrations (rs=0.36, P=0.02). Both palmitoleic/palmitic and oleic/stearic indices correlated with waist circumference (r=0.47, P=0.001; r=0.37, P=0.01). The VLDL oleic/stearic index was higher in GDM. CONCLUSION The elevated total oleic/stearic index suggests increased lipogenesis in GDM newborns. Factors in addition to glucose supply may influence fetal SCD1 activity.
Collapse
Affiliation(s)
- Jennifer K. Yee
- Department of Pediatrics, Division of Endocrinology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
| | - Catherine S. Mao
- Department of Pediatrics, Division of Endocrinology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
| | - Michael G. Ross
- Department of Obstetrics and Gynecology, Los Angeles Biomedical Research at Harbor-UCLA Medical Center
| | - W. N. Paul Lee
- Department of Pediatrics, Division of Endocrinology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
| | - Mina Desai
- Department of Obstetrics and Gynecology, Los Angeles Biomedical Research at Harbor-UCLA Medical Center
| | - Audrey Toda
- Department of Obstetrics and Gynecology, Los Angeles Biomedical Research at Harbor-UCLA Medical Center
| | - Siri L. Kjos
- Department of Obstetrics and Gynecology, Los Angeles Biomedical Research at Harbor-UCLA Medical Center
| | - Rebecca A. Hicks
- Department of Pediatrics, Division of Endocrinology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
| | - Mary E. Patterson
- Department of Pediatrics, Division of Endocrinology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
| |
Collapse
|
|
29
|
Sahini N, Borlak J. Recent insights into the molecular pathophysiology of lipid droplet formation in hepatocytes. Prog Lipid Res 2014; 54:86-112. [PMID: 24607340 DOI: 10.1016/j.plipres.2014.02.002] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 02/17/2014] [Accepted: 02/21/2014] [Indexed: 12/11/2022]
Abstract
Triacyglycerols are a major energy reserve of the body and are normally stored in adipose tissue as lipid droplets (LDs). The liver, however, stores energy as glycogen and digested triglycerides in the form of fatty acids. In stressed condition such as obesity, imbalanced nutrition and drug induced liver injury hepatocytes accumulate excess lipids in the form of LDs whose prolonged storage leads to disease conditions most notably non-alcoholic fatty liver disease (NAFLD). Fatty liver disease has become a major health burden with more than 90% of obese, nearly 70% of overweight and about 25% of normal weight patients being affected. Notably, research in recent years has shown LD as highly dynamic organelles for maintaining lipid homeostasis through fat storage, protein sorting and other molecular events studied in adipocytes and other cells of living organisms. This review focuses on the molecular events of LD formation in hepatocytes and the importance of cross talk between different cell types and their signalling in NAFLD as to provide a perspective on molecular mechanisms as well as possibilities for different therapeutic intervention strategies.
Collapse
Affiliation(s)
- Nishika Sahini
- Centre for Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany
| | - Jürgen Borlak
- Centre for Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany.
| |
Collapse
|
|
30
|
Crume TL, Scherzinger A, Stamm E, McDuffie R, Bischoff KJ, Hamman RF, Dabelea D. The long-term impact of intrauterine growth restriction in a diverse U.S. cohort of children: the EPOCH study. Obesity (Silver Spring) 2014; 22:608-15. [PMID: 23836432 PMCID: PMC4437590 DOI: 10.1002/oby.20565] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 06/17/2013] [Accepted: 06/17/2013] [Indexed: 01/29/2023]
Abstract
OBJECTIVE To explore the long-term impact of intrauterine growth restriction (IUGR) among a diverse, contemporary cohort of U.S. children. DESIGN AND METHODS A retrospective cohort of 42 children exposed to IUGR and 464 unexposed who were members of Kaiser Permanente of Colorado. Height and weight measurements since birth and measures of abdominal adiposity and insulin-resistance were measured at an average age of 10.6 (±1.3) years. RESULTS Infants born IUGR experienced "catch-up growth" in the first 12 months of life at a rate of 3.58 kg/m² compared to 2.36 kg/m² in unexposed infants (P = 0.01). However, after 1 year of age, no differences in BMI growth velocity were observed. Nevertheless children exposed to IUGR had higher waist circumference (67.0 vs. 65.3 cm, P = 0.03), higher insulin (15.2 vs. 11.0 μU/ml, P = 0.0002), higher HOMA-IR (2.8 vs. 2.3, P = 0.03), and lower adiponectin levels (9.0 vs. 12.0 μg/ml, P = 0.003) in adolescence, independent of other childhood and maternal factors. CONCLUSIONS Our data from a contemporary US cohort suggests that children exposed to IUGR have increased abdominal fat and increased insulin resistance biomarkers despite no differences in BMI growth patterns beyond 12 months of age. These data provide further support for the fetal programming hypothesis.
Collapse
Affiliation(s)
- Tessa L Crume
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO
| | - Ann Scherzinger
- Department of Radiology, University of Colorado School of Medicine, Aurora, CO
| | - Elizabeth Stamm
- Department of Radiology, University of Colorado School of Medicine, Aurora, CO
| | - Robert McDuffie
- Department of Obstetrics and Gynecology, Kaiser Permanente of Colorado, Denver, CO
| | - Kimberly J. Bischoff
- Department of Obstetrics and Gynecology, Kaiser Permanente of Colorado, Denver, CO
| | - Richard F. Hamman
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO
| |
Collapse
|
|
31
|
Martin RM, Patel R, Oken E, Thompson J, Zinovik A, Kramer MS, Vilchuck K, Bogdanovich N, Sergeichick N, Foo Y, Gusina N. Filter paper blood spot enzyme linked immunoassay for adiponectin and application in the evaluation of determinants of child insulin sensitivity. PLoS One 2013; 8:e71315. [PMID: 23936498 PMCID: PMC3731301 DOI: 10.1371/journal.pone.0071315] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Accepted: 06/27/2013] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT). METHODS We quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose. RESULTS In the validation study, mean intra-assay coefficients of variation (n=162) were 15%, 13% and 10% for 'low' (6.78 µg/ml), 'medium' (18.18 µg/ml) and 'high' (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n=40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3-133%. Bloodspot adiponectin was stable for at least 30 months at -80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose. CONCLUSIONS Bloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies.
Collapse
Affiliation(s)
- Richard M Martin
- School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
[Non-alcoholic fatty liver disease in obese children and adolescents]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56:517-27. [PMID: 23529597 DOI: 10.1007/s00103-012-1639-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adolescents in industrialized countries. Recent studies have demonstrated a prevalence rate of NAFLD in overweight and obese children and adolescents in Germany of up to 30%. The spectrum of NAFLD ranges from pure fatty infiltration (simple steatosis) to inflammation (steatohepatitis, synonymous NASH) to fibrosis and cirrhosis. Age, gender, ethnicity, insulin resistance, and sex steroids are implicated in the pathogenesis of NAFLD in childhood and adolescence. Moreover, NAFLD in the pediatric age group is associated with marked cardiovascular comorbidities. This review focuses on current data regarding epidemiology, pathophysiology, comorbidities, and treatment of NAFLD in children and adolescents.
Collapse
|
|
33
|
Samara A, Ventura EE, Alfadda AA, Goran MI. Use of MRI and CT for fat imaging in children and youth: what have we learned about obesity, fat distribution and metabolic disease risk? Obes Rev 2012; 13:723-32. [PMID: 22520361 DOI: 10.1111/j.1467-789x.2012.00994.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Childhood obesity is a matter of great concern for public health. Efforts have been made to understand its impact on health through advanced imaging techniques. An increasing number of studies focus on fat distribution and its associations with metabolic risk, in interaction with genetics, environment and ethnicity, in children. The present review is a qualitative synthesis of the existing literature on visceral and subcutaneous abdominal, intrahepatic and intramuscular fat. Our search revealed 80 original articles. Abdominal as well as ectopic fat depots are prevalent already in childhood and contribute to abnormal metabolic parameters, starting early in life. Visceral, hepatic and intramuscular fat seem to be interrelated but their patterns as well as their independent contribution on metabolic risk are not clear. Some ethnic-specific characteristics are also prevalent. These results encourage further research in childhood obesity by using imaging techniques such as magnetic resonance imaging and computed tomography. These imaging methods can provide a better understanding of fat distribution and its relationships with metabolic risk, compared to less detailed fat and obesity assessment. However, studies on bigger samples and with a prospective character are warranted.
Collapse
Affiliation(s)
- A Samara
- Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | | | | | | |
Collapse
|
|
34
|
Harwood HJ. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology 2012; 63:57-75. [DOI: 10.1016/j.neuropharm.2011.12.010] [Citation(s) in RCA: 157] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2011] [Revised: 11/28/2011] [Accepted: 12/09/2011] [Indexed: 02/06/2023]
|
|
35
|
Nascimento H, Costa E, Rocha-Pereira P, Rego C, Mansilha HF, Quintanilha A, Santos-Silva A, Belo L. Cardiovascular risk factors in portuguese obese children and adolescents: impact of small reductions in body mass index imposed by lifestyle modifications. Open Biochem J 2012; 6:43-50. [PMID: 22629286 PMCID: PMC3358715 DOI: 10.2174/1874091x01206010043] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2011] [Revised: 10/12/2011] [Accepted: 10/30/2011] [Indexed: 11/22/2022] Open
Abstract
Objectives: Evaluate cardiovascular risk factors in Portuguese obese children and adolescents and the long-term effects of lifestyle modifications on such risk factors. Design: Transversal cohort study and longitudinal study. Setting: University Hospital S. João and Children’s Hospital Maria Pia, Porto. Patients/Participants: 148 obese children and adolescents [81 females (54.7%); mean age of 11.0 years] and 33 controls (sex and age matched) participated in a cross-sectional study. Sixty obese patients agreed to participate in an one year longitudinal study after medical and nutritionist appointments to improve lifestyle modification; a substantial body mass index (BMI) reduction was defined by a decrease in BMI z-score (BMI z-sc) of 0.3 or more over the studied period. Main Outcome measures: Lipid profile (triglycerides, cholesterol, HDLc, LDLc, lipoprotein (a), apolipoproteins A and B) and circulating levels of C-reactive protein (CRP), adiponectin, glucose, and insulin. Results: Compared with the lean children, obese patients demonstrated statistically significantly higher insulin resistance index [Homeostasis model assessment (HOMA)], and triglycerides, LDLc, apolipoprotein (apo) B, insulin and CRP concentrations, whereas their HDLc and apo A levels were significantly lower (cross-sectional study). In the longitudinal study (n=60), a substantial BMI reduction occurred in 17 (28.3%) obese patients which led to a significant reduction in triglycerides, cholesterol, LDLc, apo B, glucose and insulin levels and in HOMA. The ΔBMI values over the studied period correlated inversely and significantly with BMI (P<0.001) and HOMA (P=0.026) values observed at baseline. In multiple linear regression analysis, BMI at baseline remained associated to changes in BMI over the studied period (standardised Beta: -0.271, P=0.05). Conclusion: Our data demonstrates that small reductions in BMI-zc, imposed by lifestyle modifications in obese children and adolescents, improve the cardiovascular risk profile of such patients. Furthermore, patients with higher BMI and/or insulin resistance seem to experience a greater relative reduction in their BMI after lifestyle improvements.
Collapse
Affiliation(s)
- Henrique Nascimento
- Departamento de Bioquímica, Faculdade de Farmácia, Universidade do Porto, 4050-047 Porto, Portugal
| | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Scott HA, Gibson PG, Garg ML, Pretto JJ, Morgan PJ, Callister R, Wood LG. Relationship between body composition, inflammation and lung function in overweight and obese asthma. Respir Res 2012; 13:10. [PMID: 22296721 PMCID: PMC3329414 DOI: 10.1186/1465-9921-13-10] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2011] [Accepted: 02/01/2012] [Indexed: 01/14/2023] Open
Abstract
Background The obese-asthma phenotype is not well defined. The aim of this study was to examine both mechanical and inflammatory influences, by comparing lung function with body composition and airway inflammation in overweight and obese asthma. Methods Overweight and obese (BMI 28-40 kg/m2) adults with asthma (n = 44) completed lung function assessment and underwent full-body dual energy x-ray absorptiometry. Venous blood samples and induced sputum were analysed for inflammatory markers. Results In females, android and thoracic fat tissue and total body lean tissue were inversely correlated with expiratory reserve volume (ERV). Conversely in males, fat tissue was not correlated with lung function, however there was a positive association between android and thoracic lean tissue and ERV. Lower body (gynoid and leg) lean tissue was positively associated with sputum %neutrophils in females, while leptin was positively associated with android and thoracic fat tissue in males. Conclusions This study suggests that both body composition and inflammation independently affect lung function, with distinct differences between males and females. Lean tissue exacerbates the obese-asthma phenotype in females and the mechanism responsible for this finding warrants further investigation.
Collapse
Affiliation(s)
- Hayley A Scott
- Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW Australia
| | | | | | | | | | | | | |
Collapse
|
|
37
|
Chen MJ, Yeh YT, Lee KT, Tsai CJ, Lee HH, Wang SN. The promoting effect of adiponectin in hepatocellular carcinoma. J Surg Oncol 2012; 106:181-7. [PMID: 22287480 DOI: 10.1002/jso.23059] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Accepted: 01/09/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Adipokines may explain the newly established association of obesity with hepatocellular carcinoma (HCC). This study investigated if adiponectin levels in HCC patients differed from healthy controls and their potential effect in the development of HCC. METHODS Radioimmunoassay was used to determine serum adiponectin levels of 65 HCC patients and 165 healthy controls. The expressions of adiponectin protein in the tumor and adjacent non-tumor parts were examined by the immunoblotting method. Cell proliferation assays were used to assess the bioeffects of adiponectin in two human liver cancer cell lines. RESULTS Serum adiponectin levels were significantly higher in the HCC patients than the controls. Significant correlations of serum adiponectin levels with serum triglyceride levels and insulin resistance were found in the controls, but not in the HCC patients. In contrast, serum adiponectin levels significantly correlated with serum albumin and alkaline phosphatase levels in the HCC patients, but this trend was not observed in the controls. The expression pattern of adiponectin protein between the paired tumor and adjacent non-tumor tissues significantly correlated with tumor size. In vitro, adiponectin increased cell proliferation in a dose-dependent manner. CONCLUSIONS Increased adiponectin expressions were found in HCC and this increase might contribute to tumor growth.
Collapse
Affiliation(s)
- Ming-Jenn Chen
- Division of General Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan, R.O.C
| | | | | | | | | | | |
Collapse
|
|
38
|
Saxena A, Chumanevich A, Fletcher E, Larsen B, Lattwein K, Kaur K, Fayad R. Adiponectin deficiency: role in chronic inflammation induced colon cancer. Biochim Biophys Acta Mol Basis Dis 2011; 1822:527-36. [PMID: 22198319 DOI: 10.1016/j.bbadis.2011.12.006] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2011] [Revised: 12/05/2011] [Accepted: 12/06/2011] [Indexed: 12/20/2022]
Abstract
Adiponectin (APN), an adipokine, exerts an anti-inflammatory and anti-cancerous activity with its role in glucose and lipid metabolism and its absence related to several obesity related malignancies including colorectal cancer. The aim of this study is to determine the effect of APN deficiency on the chronic inflammation-induced colon cancer. This was achieved by inducing inflammation and colon cancer in both APN knockout (KO) and C57B1/6 wild type (WT) mice. They were divided into four treatment groups (n=6): 1) control (no treatment); 2) treatment with three cycles of dextran sodium sulfate (DSS); 3) weekly doses of 1,2-dimethylhydrazine (DMH) (20mg/kg of mouse body weight) for twelve weeks; 4) a single dose of DMH followed by 3 cycles of DSS (DMH+DSS). Mice were observed for diarrhea, stool hemoccult, and weight loss and were sacrificed on day 153. Tumor area and number were counted. Colonic tissues were collected for Western blot and immunohistochemistry analyses. APNKO mice were more protected than WT mice from DSS induced colitis during first DSS cycle, but lost this protection during the second and the third DSS cycles. APNKO mice had significantly severe symptoms and showed greater number and larger area of tumors with higher immune cell infiltration and inflammation than WT mice. This result was further confirmed by proteomic study including pSTAT3, pAMPK and Cox-2 by western blot and Immunohistochemistry. Conclusively, APN deficiency contributes to inflammation-induced colon cancer. Hence, APN may play an important role in colorectal cancer prevention by modulating genes involved in chronic inflammation and tumorigenesis.
Collapse
Affiliation(s)
- Arpit Saxena
- Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, 921 Assembly Street, Room 402, USA
| | | | | | | | | | | | | |
Collapse
|
|
39
|
Chacko SK, Ordonez J, Sauer PJJ, Sunehag AL. Gluconeogenesis is not regulated by either glucose or insulin in extremely low birth weight infants receiving total parenteral nutrition. J Pediatr 2011; 158:891-6. [PMID: 21324479 PMCID: PMC3095705 DOI: 10.1016/j.jpeds.2010.12.040] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2010] [Revised: 11/08/2010] [Accepted: 12/23/2010] [Indexed: 12/01/2022]
Abstract
OBJECTIVE To determine potential factors regulating gluconeogenesis (GNG) in extremely low birth weight infants receiving total parenteral nutrition. STUDY DESIGN Seven infants (birth weight, 0.824 ± 0.068 kg; gestational age, 25.4 ± 0.5 weeks; postnatal age, 3.3 ± 0.2 days) were studied for 11 hours, with parenteral lipid and amino acid therapy continued at prestudy rates. Glucose was supplied at prestudy rates for the first 5 hours (period 1) and was then reduced to 6 mg/kg·min for 1 hour and further to ~3 mg/kg·min for 5 hours (period 2). A total of 2.5 mg/kg·min of the glucose was replaced by [U-(13)C]glucose throughout the study for measurements of glucose production and GNG. Concentrations of glucose, insulin, glucagons, and cortisol were determined. RESULTS GNG and glucose production remained unchanged (2.12 ± 0.23 vs. 1.84 ± 0.25 mg/kg·min [P = NS] and 2.44 ± 0.27 vs. 2.51 ± 0.31 mg/kg·min [P = NS], respectively), despite a 60% reduction of the glucose infusion rate and subsequent 30% (124.7 ± 10.8 to 82.6 ± 8.9 mg/dL; P = .009) and 70% (26.9 ± 4.7 to 6.6 ± 0.4 μU/mL; P = .002) decreases in glucose and insulin concentrations, respectively. Cortisol and glucagon concentrations remained unchanged. CONCLUSION In extremely low birth weight infants receiving total parenteral nutrition, GNG is a continuous process that is not affected by infusion rates of glucose or concentrations of glucose or insulin.
Collapse
Affiliation(s)
- Shaji K. Chacko
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| | - Jorge Ordonez
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| | - Pieter J. J. Sauer
- Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Agneta L. Sunehag
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| |
Collapse
|
|
40
|
Yeste D, Carrascosa A. [Obesity-related metabolic disorders in childhood and adolescence]. An Pediatr (Barc) 2011; 75:135.e1-9. [PMID: 21571600 DOI: 10.1016/j.anpedi.2011.03.025] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2011] [Revised: 03/22/2011] [Accepted: 03/30/2011] [Indexed: 11/29/2022] Open
Abstract
Obesity is the most frequent nutritional disorder in childhood and adolescence. The rise in its prevalence and severity has underlined the numerous and significant obesity-related metabolic disorders. Altered glucose metabolism, manifested as impaired glucose tolerance, appears early in severely obese children and adolescents. Obese young people with glucose intolerance are characterized by marked peripheral insulin resistance and relative beta-cell failure. Lipid deposition in muscle and the visceral compartment, and not only obesity per se, is related to increased peripheral insulin resistance, the triggering factor of the metabolic syndrome. Other elements of the metabolic syndrome, such as dyslipidaemia, and hypertension, are already present in obese youngsters and worsen with the degree of obesity. The long-term impact of obesity-related insulin resistance on cardiovascular morbidity in these patients is expected to emerge as these youngsters become young adults.
Collapse
Affiliation(s)
- D Yeste
- Servicio de Pediatría, Unidades de Endocrinología y Obesidad Pediátrica, Hospital Universitario Vall d' Hebron, Barcelona, Universidad Autónoma de Barcelona, España.
| | | |
Collapse
|
|
41
|
Bredella MA, Torriani M, Ghomi RH, Thomas BJ, Brick DJ, Gerweck AV, Harrington LM, Miller KK. Adiponectin is inversely associated with intramyocellular and intrahepatic lipids in obese premenopausal women. Obesity (Silver Spring) 2011; 19:911-6. [PMID: 21151017 PMCID: PMC3607306 DOI: 10.1038/oby.2010.296] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy ((1)H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 ± 6.6 kg/m(2)) who underwent (1)H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMA(IR)), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMA(IR). Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin.
Collapse
Affiliation(s)
- Miriam A Bredella
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
| | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Affiliation(s)
- Ebe D'Adamo
- Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA
| | | |
Collapse
|
|
43
|
Hypothalamic Obesity following Craniopharyngioma Surgery: Results of a Pilot Trial of Combined Diazoxide and Metformin Therapy. INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY 2011; 2011:417949. [PMID: 21603206 DOI: 10.1155/2011/417949] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2010] [Accepted: 02/07/2011] [Indexed: 01/08/2023]
Abstract
Objective. To assess the effect of combined diazoxide-metformin therapy in obese adolescents treated for craniopharyngioma. Design. A prospective open-label 6-month pilot treatment trial in 9 obese subjects with craniopharyngioma. Diazoxide (2 mg/kg divided b.i.d., maximum 200 mg/day) and metformin (1000 mg b.i.d.). Whole body insulin sensitivity index (WBISI) and area-under-the-curve insulin (AUC(ins)) were calculated. Results. Seven subjects completed: 4M/3F, mean ± SD age 15.4 ± 2.9 years, weight 99.7 ± 26.3 kg, BMI 35.5 ± 5.6 kg/m(2), and BMI SDS 2.3 ± 0.3. Two were withdrawn due to vomiting and peripheral edema. Of participants completing the study, the mean ± SD weight gain, BMI, and BMI SDS during the 6 months were reduced compared to the 6 months prestudy (+1.2 ± 5.9 versus +9.5 ± 2.7 kg, P = .004; -0.3 ± 2.3 versus +2.2 ± 1.5 kg/m(2), P = .04; -0.04 ± 0.15 versus +0.11 ± 0.08, P = .021, resp.). AUC(ins) correlated with weight loss (r = 0.82, P = .02) and BMI decrease (r = 0.96, P = .009). Conclusion. Combined diazoxide-metformin therapy was associated with reduced weight gain in patients with hypothalamic obesity. AUC(ins) at study commencement predicted effectiveness of the treatment.
Collapse
|
|
44
|
Cali AMG, Pierpont BM, Taksali SE, Allen K, Shaw MM, Savoye M, Caprio S. Rosiglitazone improves glucose metabolism in obese adolescents with impaired glucose tolerance: a pilot study. Obesity (Silver Spring) 2011; 19:94-9. [PMID: 20467418 DOI: 10.1038/oby.2010.109] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Impaired glucose tolerance (IGT) is a prediabetic state fueling the rising prevalence of type 2 diabetes mellitus (T2DM) in adolescents with marked obesity. Given the importance of insulin resistance, the poor β-cell compensation and the altered fat partitioning as underlying defects associated with this condition, it is crucial to determine the extent to which these underlying abnormalities can be reversed in obese adolescents. We tested, in a pilot study, whether rosiglitazone (ROSI) restores normal glucose tolerance (NGT) in obese adolescents with IGT by improving insulin sensitivity and β-cell function. In a small randomized, double-blind, placebo (PLA)-controlled study, lasting 4 months, 21 obese adolescents with IGT received either ROSI (8 mg daily) (n = 12, 5M/7F, BMI z-score 2.44 ± 0.11) or PLA (n = 9, 4M/5F, BMI z-score 2.41 ± 0.09). Before and after treatment, all subjects underwent oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, magnetic resonance imaging, and (1)H NMR assessment. After ROSI treatment, 58% of the subjects converted to NGT compared to 44% in the PLA group (P = 0.528). Restoration of NGT was associated with a significant increase in insulin sensitivity (P < 0.04) and a doubling in the disposition index (DI) (P < 0.04), whereas in the PLA group, these changes were not significant. The short-term use of ROSI appears to be safe in obese adolescents with IGT. ROSI restores NGT by increasing peripheral insulin sensitivity and β-cell function, two principal pathophysiological abnormalities of IGT.
Collapse
Affiliation(s)
- Anna M G Cali
- Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA
| | | | | | | | | | | | | |
Collapse
|
|
45
|
Cui J, Wu X, Andrel J, Falkner B. Relationships of total adiponectin and molecular weight fractions of adiponectin with free testosterone in African men and premenopausal women. J Clin Hypertens (Greenwich) 2010; 12:957-63. [PMID: 21122061 DOI: 10.1111/j.1751-7176.2010.00383.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Adiponectin, a protein secreted by adipose tissue, has anti-inflammatory, antithrombogenic, and antidiabetogenic effects. Lower plasma adiponectin levels are present in diabetes, obesity, and the metabolic syndrome. Adiponectin levels are higher in women compared with men. The purpose of this study was to determine whether there is a relationship between total adiponectin, or the molecular weight fractions of adiponectin, and testosterone levels in African American men and premenopausal women. A sample (N=48) of men and premenopausal women was selected based on high and low serum-free testosterone level. All patients had data on blood pressure, metabolic risk factors, and sex hormone levels. Stored plasma samples were assayed for total adiponectin. Molecular weight fractions of adiponectin were separated by gel electrophoresis and quantified by Western blot. Data analysis compared adiponectin (total and fractions) levels with androgen status in both sexes. Among men with high testosterone levels, all fractions of adiponectin were significantly lower than those in men with low testosterone (P<.05). In women with high testosterone, total adiponectin (P=.02) and all fractions of molecular weight adiponectin (P<.05) were lower compared with those in women with low testosterone. Plasma adiponectin levels are lower in both men and premenopausal women with relatively higher testosterone levels.
Collapse
Affiliation(s)
- Jie Cui
- Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA
| | | | | | | |
Collapse
|
|
46
|
Metabolic syndrome and ectopic fat deposition: what can CT and MR provide? Acad Radiol 2010; 17:1302-12. [PMID: 20605492 DOI: 10.1016/j.acra.2010.03.019] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2010] [Revised: 03/26/2010] [Accepted: 03/29/2010] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Metabolic syndrome affects 20-30% of adults and is increasing in prevalence, making it a leading public health issue. Radiologists often encounter images of obese patients during routine studies and are in a unique position to address the importance of excess fat and need to be aware of the spectrum of pathologic consequences in different organ systems. In this review, the role of CT and MR imaging in assessment of patients with metabolic syndrome will be reviewed and the constellation of structural and functional changes in the major affected organ systems due to ectopic fatty deposition will be discussed. METHODS We specifically discuss the pathophysiology of metabolic syndrome, visceral versus subcutaneous obesity, cardiac lipomatosis, nonalcoholic fatty liver disease, nonalcoholic fatty pancreas disease, and fat deposition in other organs. CONCLUSION Many of the multisystem manifestations of metabolic syndrome can be visualized on routine CT and MR images and radiologists can provide clinicians with important data regarding anatomic and pathologic distribution of fat in different organs. Perhaps the visualization of the fatty changes will provide tangible evidence to motivate patients to begin lifestyle modification.
Collapse
|
|
47
|
Nishihara M, Sonoda M, Matsunami K, Yanagihara K, Yonemoto N, Ida S, Namba F, Shimomura I, Yanagihara I, Waguri M. Birth length is a predictor of adiponectin levels in Japanese young children. J Pediatr Endocrinol Metab 2010; 23:913-20. [PMID: 21175090 DOI: 10.1515/jpem.2010.146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Adiponectin has been shown to be inversely related to birth weight in schoolchildren and adolescents. However, the available information regarding a relation between birth size and adiponectin in infants and preschoolers is limited. METHODS A longitudinal study was conducted among healthy Japanese children, and serum adiponectin levels were measured at consecutive visits. The effect of sex, gestational age, birth length, birth weight, or placental weight on adiponectin was analyzed by using a linear mixed model for repeated measures. RESULTS Eighty-three children were evaluated. The age range at the first visit was 0.07-5.3 years. A total number of 227 measurements were made, 1-12 per subject (median, 3) and the duration of follow-up ranged from 1 day to 2.3 years (median, 1.0 years). The subjects were divided into four groups according to the age at the first visit: (1) 0-2 months (n = 29), (2) 3 months to 1 year (n = 17), (3) 2-3 years (n = 19) and (4) 4-5 years (n = 18). In the multivariate model, birth length (coefficient = 3.94, 95% CI, 0.23-7.65) was an independent predictor of serum adiponectin levels in subjects aged 0-2 months. Gestational age (3.53, 1.14-5.92), birth length (-2.71, -4.90 to -0.53) and placental weight (2.58, 0.86-4.29) were independent predictors of serum adiponectin levels in subjects aged 4-5 years. CONCLUSION Birth length, not birth weight, is an independent predictor of serum adiponectin levels in Japanese young children.
Collapse
Affiliation(s)
- Masahiro Nishihara
- Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Specchia C, Scott K, Fortina P, Devoto M, Falkner B. Association of a polymorphic variant of the adiponectin gene with insulin resistance in african americans. Clin Transl Sci 2010; 1:194-9. [PMID: 20443850 DOI: 10.1111/j.1752-8062.2008.00055.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Hypertension, type 2 diabetes, and obesity are common complex disorders that contribute to cardiovascular (CV) disease. Insulin resistance increases CV risk and is present in these disorders. Adiponectin, a protein secreted by adipocytes with metabolic and vascular protective effects, is lower in obesity and insulin resistance. Several single nucleotide polymorphisms (SNP) have been identified in the adiponectin (ADIPOQ) gene. Associations of ADIPOQ polymorphisms with diabetes and obesity have been described in Caucasians and Asians. The purpose of this study was to determine if genetic variants of ADIPOQ are associated with insulin resistance and CV risk in African Americans. Metabolic traits (lipids, glucose, insulin, and insulin sensitivity) and blood pressure were measured in 273 African Americans. DNA was examined by DNA sequence analysis and SNPs of candidate genes including ADIPOQ were studied. Statistica analyses were performed by regression of the quantitative trait phenotypes on the groups defined by the SNP genotypes, adjusting for age, sex, and body mass index (BMI). SNP 712 (rs3774261) ofthe/lD/POQgene showed significant association with insulin resistance (p= 0.001). Despite the relatively small sample, our results indicate that genes that regulate adipocyte function may have a regulatory role in the expression of metabolic traits in obesity-associated chronic disease.
Collapse
Affiliation(s)
- Claudia Specchia
- Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy
| | | | | | | | | |
Collapse
|
|
49
|
Abstract
Insulin resistance has long been associated with obesity. More than 40 years ago, Randle and colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through inhibition of glycolysis at key points. However, work over the past two decades has shown that lipid-induced insulin resistance in skeletal muscle stems from defects in insulin-stimulated glucose transport activity. The steatotic liver is also resistant to insulin in terms of inhibition of hepatic glucose production and stimulation of glycogen synthesis. In muscle and liver, the intracellular accumulation of lipids-namely, diacylglycerol-triggers activation of novel protein kinases C with subsequent impairments in insulin signalling. This unifying hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, lipodystrophy, and ageing; and the insulin-sensitising effects of thiazolidinediones.
Collapse
Affiliation(s)
- Varman T Samuel
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536-8012, USA
| | | | | |
Collapse
|
|
50
|
Sood A, Qualls C, Li R, Schuyler M, Beckett WS, Smith LJ, Thyagarajan B, Lewis CE, Jacobs DR. Lean mass predicts asthma better than fat mass among females. Eur Respir J 2010; 37:65-71. [PMID: 20525713 DOI: 10.1183/09031936.00193709] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The obesity phenotype associated with asthma is not known. Our objective was to define the relative contribution of various distributions of fat and lean mass to asthma prevalence. Data were obtained from 2,525 participants (including 1,422 females) who underwent dual-energy X-ray absorptiometry (DEXA) at the year 20 examination in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Total, truncal, arm and leg distributions of fat and lean mass were adjusted to the person's height. Self-reported asthma was the outcome. Asthma among females was associated with greater total fat mass, arm fat mass, total lean mass, truncal lean mass and arm lean mass. Among males, none of these mass measures were significantly associated with asthma. Among females, the association with asthma was stronger for total lean mass than for total fat mass. Further, among various regional distributions of lean and fat mass in females, truncal lean mass was the strongest predictor. Total lean mass is more strongly associated with asthma than total fat mass among females. These findings are contrary to the popular perception that excess physiological fat drives the obesity-asthma association. Rather, we hypothesise that ectopic fat within the "lean" tissues drives this association among females.
Collapse
Affiliation(s)
- A Sood
- Dept of Medicine, University of New Mexico, School of Medicine, Albuquerque, NM 87131, USA.
| | | | | | | | | | | | | | | | | | | |
Collapse
|