scholarly journals Association between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass

2008 ◽  
Vol 93 (11) ◽  
pp. 4486-4493 ◽  
Author(s):  
Anders Rinnov Nielsen ◽  
Pernille Hojman ◽  
Christian Erikstrup ◽  
Christian Philip Fischer ◽  
Peter Plomgaard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fat Mass ◽  
Negative Association ◽  
Tissue Mass ◽  
Adipose Tissue Mass ◽  
Interleukin 15 ◽  
Total Fat

Objective: IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way regulate adipose tissue mass. Design: The relation between skeletal muscle IL-15 mRNA expression, plasma IL-15, and adipose tissue mass was studied in 199 humans divided into four groups on the basis of obesity and type 2 diabetes. Furthermore, using a DNA electrotransfer model, we assessed the effect of IL-15 overexpression in skeletal muscle of mice. Results: In humans, multiple regression analysis showed a negative association between plasma IL-15 and total fat mass (P < 0.05), trunk fat mass (P < 0.01), and percent fat mass (P < 0.05), independent of type 2 diabetes. Negative associations were also found between muscle IL-15 mRNA and obesity parameters. IL-15 overexpression in skeletal muscle of mice reduced trunk fat mass but not sc fat mass. Conclusions: Our results indicate that IL-15 may be a regulator of trunk fat mass.

scholarly journals Associations of Haplotypes Upstream ofIRS1with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal MuscleLOC646736mRNA Levels

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Selma M. Soyal ◽  
Thomas Felder ◽  
Simon Auer ◽  
Hannes Oberkofler ◽  
Bernhard Iglseder ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipid Profile ◽  
Mrna Levels ◽  
Tissue Mass ◽  
Cross Sectional ◽  
Adipose Tissue Mass

The genomic region ~500 kb upstream ofIRS1has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited from the same geographic region. From 16 possible haplotypes, 6 haplotypes with frequencies >0.01 were observed. We identified one haplotype that was protective against insulin resistance (determined by HOMA-IR and fasting plasma insulin levels), type 2 diabetes, an adverse lipid profile, increased C-reactive protein, and asymptomatic atherosclerotic disease (assessed by intima media thickness of the common carotid arteries). BMI and total adipose tissue mass as well as visceral and subcutaneous adipose tissue mass did not differ between the reference and protective haplotypes. In 92 subjects, we observed an association of the protective haplotype with higher skeletal muscle mRNA levels ofLOC646736, which is located in the same haplotype block as the informative SNPs and is mainly expressed in skeletal muscle, but only at very low levels in liver or adipose tissues. These data suggest a role forLOC646736in human insulin resistance and warrant further studies on the functional effects of this locus.

Reducing visceral adipose tissue mass is essential for improving endothelial function in type 2 diabetes prone individuals

2010 ◽  
Vol 212 (2) ◽  
pp. 575-579 ◽  
Author(s):  
K. Rittig ◽  
A. Hieronimus ◽  
C. Thamer ◽  
J. Machann ◽  
A. Peter ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Endothelial Function ◽  
Visceral Adipose Tissue ◽  
Tissue Mass ◽  
Adipose Tissue Mass ◽  
Visceral Adipose

scholarly journals Chemotactic cytokines, obesity and type 2 diabetes:in vivoandin vitroevidence for a possible causal correlation?

2009 ◽  
Vol 68 (4) ◽  
pp. 378-384 ◽  
Author(s):  
Henrike Sell ◽  
Jürgen Eckel
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Obese Patients ◽  
Tissue Mass ◽  
Tissue Biology ◽  
Wide Range ◽  
Adipose Tissue Mass

A strong causal link between increased adipose tissue mass and insulin resistance in tissues such as liver and skeletal muscle exists in obesity-related disorders such as type 2 diabetes. Increased adipose tissue mass in obese patients and patients with diabetes is associated with altered secretion of adipokines, which also includes chemotactic proteins. Adipose tissue releases a wide range of chemotactic proteins including many chemokines and chemerin, which are interesting targets for adipose tissue biology and for biomedical research in obesity and obesity-related diseases. This class of adipokines may be directly linked to a chronic state of low-grade inflammation and macrophage infiltration in adipose tissue, a concept intensively studied in adipose tissue biology in recent years. The inflammatory state of adipose tissue in obese patients may be the most important factor linking increased adipose tissue mass to insulin resistance. Furthermore, chemoattractant adipokines may play an important role in this situation, as many of these proteins possess biological activity beyond the recruitment of immune cells including effects on adipogenesis and glucose homeostasis in insulin-sensitive tissues. The present review provides a summary of experimental evidence of the role of adipose tissue-derived chemotactic cytokines and their function in insulin resistancein vivoandin vitro.

scholarly journals Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats

2005 ◽  
Vol 34 (2) ◽  
pp. 299-315 ◽  
Author(s):  
Young Ho Suh ◽  
Younyoung Kim ◽  
Jeong Hyun Bang ◽  
Kyoung Suk Choi ◽  
June Woo Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats. These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.

scholarly journals The Effect of a Low GI Diet on Truncal Fat Mass and Glycated Hemoglobin in South Indians with Type 2 Diabetes—A Single Centre Randomized Prospective Study

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 179 ◽  
Author(s):  
Nivedita Pavithran ◽  
Harish Kumar ◽  
Arun Somasekharan Menon ◽  
Gopala Krishna Pillai ◽  
Karimassery Ramaiyer Sundaram ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Composition ◽  
Fat Mass ◽  
South India ◽  
Glycated Hemoglobin ◽  
Diet Group ◽  
Control Group ◽  
South Indian ◽  
Total Fat

Background: There has been no previous study that has investigated the effect of a low glycemic index (LGI) diet with local recipes of South Indian cuisine on the body fat composition using dual-energy X-ray absorptiometry (DXA). Truncal obesity has been associated with the risk of metabolic disorders and cardiovascular diseases. Aim: The aim of this study was to examine the effect of a low GI diet on glycemic control and body composition in people with type 2 diabetes in South India. Method: This was a prospective and randomized controlled study that was conducted over a period of 24 weeks. A total of 40 participants were recruited from the Department of Endocrinology and Diabetes Outpatient in Kerala, South India. All the patients had type 2 diabetes and were randomly assigned and given advice and instructions to follow either a low GI diet plan (n = 18) or their usual diet, which served as control (n = 18). The advice was reinforced throughout the study period. Dietary compliance was evaluated based on a 24 h dietary recall at weeks 3, 11, 12, 18, 23, and 24. The age of the subjects ranged from 35 to 65 years. Anthropometric, body composition, and cardio-metabolic parameters were measured according to standard procedures. T-tests were conducted to compare differences between intervention and control groups and the Pearson correlation coefficient was used to evaluate associations between the variables. Results: There were significant reductions (p < 0.05) in the low GI diet compared to the control group with respect to weight, body mass index (BMI), and triceps skinfold thickness. Similarly, significant reductions were observed in the low GI diet group with respect to region, total fat, android, and gynoid fat mass and the differences between the groups were significant at p < 0.05. There was also a positive correlation between BMI and android fat mass (r = 0.745), total fat mass (r = 0.661), total truncal mass (r = 0.821), and truncal fat (r = 0.707). There was a significant reduction in glycated hemoglobin in the low GI diet group compared to the control group at p < 0.05. Conclusion: This study has demonstrated that there was a significant reduction (p < 0.05) of truncal obesity and glycated hemoglobin in patients with type 2 diabetes on a local diet of South Indian cuisine with low GI compared with the control.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

2017 ◽  
Vol 176 (2) ◽  
pp. R67-R78 ◽  
Author(s):  
Charlotte Brøns ◽  
Louise Groth Grunnet
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Cellular Localization ◽  
Future Research ◽  
Causal Mechanism ◽  
Increased Risk ◽  
Adipose Tissue Expandability

Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver.

scholarly journals 4126 Intermuscular adipose tissue secretes pro-inflammatory, extracellular matrix, and lipid signals related to insulin resistance and type 2 diabetes

2020 ◽  
Vol 4 (s1) ◽  
pp. 9-9
Author(s):  
Darcy Kahn ◽  
Simona Zarini ◽  
Emily Macias ◽  
Amanda Garfield ◽  
Kathleen Harrison ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Functional Role ◽  
Vastus Lateralis ◽  
Laparoscopic Bariatric Surgery ◽  
Intermuscular Adipose Tissue

OBJECTIVES/GOALS: Intermuscular adipose tissue (IMAT) has been associated with insulin resistance and type 2 diabetes, yet mechanistic studies addressing the functional role of IMAT are lacking. The aim of this work was to identify novel mechanisms by which IMAT may directly impact skeletal muscle metabolism. METHODS/STUDY POPULATION: We quantified the secretome of IMAT, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) to determine if there are differences between depots in the secretion of cytokines, eicosanoids, FFAs and proteins that influence metabolic function. SAT and VAT biopsies from patients undergoing laparoscopic bariatric surgery and IMAT extracted from vastus lateralis biopsies of individuals with Obesity were cultured for 48 hours in DMEM, and the conditioned media was analyzed using nanoflow HPLC-MS, multiplex ELISAs and LC/MS/MS for proteins, cytokines and eicosanoids/FFA, respectively. RESULTS/ANTICIPATED RESULTS: IMAT secretion of various extracellular matrix proteins (fibrinogen-β, collagenV1a3, fibronectin) was significantly different than VAT and SAT. Pro-inflammatory cytokine secretion of IFNg, TNFa, IL-8 and IL-13 from IMAT was higher than VAT and significantly higher than SAT (p < 0.05). IMAT secretes significantly more pro-inflammatory eicosanoids TXB2 and PGE2 than VAT (p = 0.02, 0.05) and SAT (p = 0.01, 0.04). IMAT and VAT have significantly greater basal lipolysis assessed by FFA release rates compared to SAT (p = 0.01, 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: These data begin to characterize the disparate secretory properties of SAT, VAT and IMAT and suggest a metabolically adverse secretome of IMAT, that due to its proximity to skeletal muscle may play an important functional role in the pathogenesis of insulin resistance and type 2 diabetes.

scholarly journals Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 1069-1069
Author(s):  
Michael Boschmann ◽  
Stefan Engeli ◽  
Kerstin Dobberstein ◽  
Petra Budziarek ◽  
Anke Strauss ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Standardized Test ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Diabetic Patients ◽  
Lipid Mobilization ◽  
Postprandial Lipid

Abstract Context: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extra-pancreatic mechanisms. Objective: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. Design: Randomized, double blind, crossover study. Setting: Academic clinical research center. Patients: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m2. Intervention: Seven days treatment with the selective DPP-4 inhibitor vildagliptin or placebo. Standardized test meal on day seven. Main Outcome Measures: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin; dialysate glucose, lactate, pyruvate, glycerol. Results: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptine increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. Conclusions: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

GPCRs and Insulin Receptor Signaling in Conversation: Novel Avenues for Drug Discovery

2019 ◽  
Vol 19 (16) ◽  
pp. 1436-1444 ◽  
Author(s):  
Manveen K. Gupta ◽  
Neelakantan T. Vasudevan
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Drug Discovery ◽  
Treatment Modalities ◽  
Dpp Iv ◽  
Sulfonyl Urea ◽  
Insulin Receptor Signaling ◽  
Major Treatment

Type 2 diabetes is a major health issue worldwide with complex metabolic and endocrine abnormalities. Hyperglycemia, defects in insulin secretion and insulin resistance are classic features of type 2 diabetes. Insulin signaling regulates metabolic homeostasis by regulating glucose and lipid turnover in the liver, skeletal muscle and adipose tissue. Major treatment modalities for diabetes include the drugs from the class of sulfonyl urea, Insulin, GLP-1 agonists, SGLT2 inhibitors, DPP-IV inhibitors and Thiazolidinediones. Emerging antidiabetic therapeutics also include classes of drugs targeting GPCRs in the liver, adipose tissue and skeletal muscle. Interestingly, recent research highlights several shared intermediates between insulin and GPCR signaling cascades opening potential novel avenues for diabetic drug discovery.

scholarly journals Increased AQP7 abundance in skeletal muscle from obese men with type 2 diabetes

2018 ◽  
Vol 315 (3) ◽  
pp. E367-E373 ◽  
Author(s):  
Janne Lebeck ◽  
Esben Søndergaard ◽  
Søren Nielsen
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Protein Abundance ◽  
Tissue Samples ◽  
Triglyceride Accumulation ◽  
Meal Intake ◽  
Fasting And Refeeding ◽  
Subcutaneous Adipose

Aquaglyceroporin 7 (AQP7) facilitates the transport of glycerol across cell membranes. In mice, fasting and refeeding regulate adipose tissue AQP7 abundance, and a role in controlling triglyceride accumulation in adipose tissue has been proposed. AQP7 is also expressed in skeletal muscle, where its function remains to be determined. Here, the abundance of AQP7 in abdominal subcutaneous adipose tissue (SAT) and skeletal muscle was evaluated in the overnight fasted and postprandial state in eight lean and eight obese men with type 2 diabetes (T2D). A biopsy from SAT and muscle was collected after an overnight fast and 2 h after ingestion of a low-fat test meal. Palmitate turnover was evaluated using a [9,10-3H] palmitate dilution technique. Tissue samples were analyzed by immunoblotting. Meal intake did not affect AQP7 expression in SAT or skeletal muscle. No association between the SAT AQP7 abundance and palmitate turnover was found. SAT AQP7 abundance was similar in lean and obese T2D men, whereas muscle AQP7 abundance was more than fourfold higher in obese T2D men. In conclusion, meal intake did not affect AQP7 protein abundance in SAT or skeletal muscle. In addition, SAT AQP7 expression does not appear to be involved in the regulation of adipose tissue lipolysis. However, in contrast to SAT AQP7, skeletal muscle AQP7 protein abundance is markedly increased in obese T2D men, potentially contributing to the excess lipid accumulation in skeletal muscle in type 2 diabetes.

Sign in / Sign up

Export Citation Format

Share Document