scholarly journals ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity

2014 ◽  
Vol 55 (3) ◽  
pp. 516-523 ◽  
Author(s):  
Willeke de Haan ◽  
Alpana Bhattacharjee ◽  
Piers Ruddle ◽  
Martin H. Kang ◽  
Michael R. Hayden
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Lipid Content ◽  
Tissue Lipid

scholarly journals Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5390
Author(s):  
Qianhui Zeng ◽  
Nannan Wang ◽  
Yaru Zhang ◽  
Yuxuan Yang ◽  
Shuangshuang Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Glycolipid Metabolism ◽  
Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

DPP4 deletion in adipose tissue improves hepatic insulin sensitivity in diet-induced obesity

2020 ◽  
Vol 318 (5) ◽  
pp. E590-E599 ◽  
Author(s):  
Tania Romacho ◽  
Henrike Sell ◽  
Ira Indrakusuma ◽  
Diana Roehrborn ◽  
Tamara R. Castañeda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hepatic Insulin Sensitivity ◽  
Dipeptidyl Peptidase 4 ◽  
Diet Induced Obesity ◽  
Hepatic Fat ◽  
Igf Binding ◽  
Igf Binding Protein

Besides a therapeutic target for type 2 diabetes, dipeptidyl peptidase 4 (DPP4) is an adipokine potentially upregulated in human obesity. We aimed to explore the role of adipocyte-derived DPP4 in diet-induced obesity and insulin resistance with an adipose tissue-specific knockout (AT-DPP4-KO) mouse. Wild-type and AT-DPP4-KO mice were fed for 24 wk with a high fat diet (HFD) and characterized for body weight, glucose tolerance, insulin sensitivity by hyperinsulinemic-euglycemic clamp, and body composition and hepatic fat content. Image and molecular biology analysis of inflammation, as well as adipokine secretion, was performed in AT by immunohistochemistry, Western blot, real-time-PCR, and ELISA. Incretin levels were determined by Luminex kits. Under HFD, AT-DPP4-KO displayed markedly reduced circulating DPP4 concentrations, proving AT as a relevant source. Independently of glucose-stimulated incretin hormones, AT-DPP4-KO had improved glucose tolerance and hepatic insulin sensitivity. AT-DPP4-KO displayed smaller adipocytes and increased anti-inflammatory markers. IGF binding protein 3 (IGFBP3) levels were lower in AT and serum, whereas free IGF1 was increased. The absence of adipose DPP4 triggers beneficial AT remodeling with decreased production of IGFBP3 during HFD, likely contributing to the observed, improved hepatic insulin sensitivity.

scholarly journals SMRT Regulates Metabolic Homeostasis and Adipose Tissue Macrophage Phenotypes in Tandem

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Jonathan H Kahn ◽  
Anna Goddi ◽  
Aishwarya Sharma ◽  
Joshua Heiman ◽  
Alanis Carmona ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Hormone Receptors ◽  
Tissue Macrophage ◽  
Secreted Factors ◽  
Physiological Homeostasis

Abstract The Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) is a nuclear corepressor, regulating the transcriptional activity of many transcription factors critical for metabolic processes. While the importance of the role of SMRT in the adipocyte has been well-established, our comprehensive understanding of its in vivo function in the context of homeostatic maintenance is limited due to contradictory phenotypes yielded by prior generalized knockout mouse models. Multiple such models agree that SMRT deficiency leads to increased adiposity, although the effects of SMRT loss on glucose tolerance and insulin sensitivity have been variable. We therefore generated an adipocyte-specific SMRT knockout (adSMRT-/-) mouse to more clearly define the metabolic contributions of SMRT. In doing so, we found that SMRT deletion in the adipocyte does not cause obesity—even when mice are challenged with a high-fat diet. This suggests that adiposity phenotypes of previously described models were due to effects of SMRT loss beyond the adipocyte. However, an adipocyte-specific SMRT deficiency still led to dramatic effects on systemic glucose tolerance and adipocyte insulin sensitivity, impairing both. This metabolically deleterious outcome was coupled with a surprising immune phenotype, wherein most genes differentially expressed in the adipose tissue of adSMRT-/- mice were upregulated in pro-inflammatory pathways. Flow cytometry and conditioned media experiments demonstrated that secreted factors from knockout adipose tissue strongly informed resident macrophages to develop a pro-inflammatory, MMe (metabolically activated) phenotype. Together, these studies suggest a novel role for SMRT as an integrator of metabolic and inflammatory signals to maintain physiological homeostasis.

scholarly journals Sensitivity to insulin of glycolysis and glycogen synthesis of isolated soleus-muscle strips from sedentary, exercised and exercise-trained rats

1983 ◽  
Vol 212 (2) ◽  
pp. 453-458 ◽  
Author(s):  
J Espinal ◽  
G L Dohm ◽  
E A Newsholme
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Treadmill Training ◽  
Insulin Concentration ◽  
Maximal Stimulation ◽  
Stimulation Of

The half-maximal stimulation of the rates of glycolysis and glycogen synthesis in soleus-muscle strips from sedentary animals occurred at a concentration of insulin of about 100 microunits/ml. In soleus-muscle strips from exercise-trained rats (5 weeks of treadmill training), half-maximal stimulation of the rate of glycolysis occurred at about 10 microunits of insulin/ml, whereas that for glycogen synthesis occurred between 10 and 100 microunits of insulin/ml. The sensitivity of glycolysis to insulin after exercise training is similar to that of adipose tissue from sedentary animals. This finding suggests that, in sedentary animals, the effects of normal changes in insulin concentration may affect muscle primarily indirectly via the anti-lipolytic effect on adipose tissue, whereas after training insulin may effect the rate of glycolysis in muscle directly. A single period of exercise did not change the sensitivity of glycolysis in soleus muscle to insulin, nor probably that of glycogen synthesis. It is suggested that the improvement in insulin sensitivity of glycolysis in muscle caused by exercise-training could account, in part, for the well-established improvement in glucose tolerance and insulin sensitivity observed in man and rats after exercise-training.

Whole-body skeletal muscle mass is not related to glucose tolerance or insulin sensitivity in overweight and obese men and women

2008 ◽  
Vol 33 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Jennifer L. Kuk ◽  
Katherine Kilpatrick ◽  
Lance E. Davidson ◽  
Robert Hudson ◽  
Robert Ross
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Visceral Adipose Tissue ◽  
Skeletal Muscle Mass ◽  
Whole Body ◽  
Men And Women ◽  
Visceral Adipose

The relationship between skeletal muscle mass, visceral adipose tissue, insulin sensitivity, and glucose tolerance was examined in 214 overweight or obese, but otherwise healthy, men (n = 98) and women (n = 116) who participated in various exercise and (or) weight-loss intervention studies. Subjects had a 75 g oral glucose tolerance test and (or) insulin sensitivity measures by a 3 h hyperinsulinemic–euglycemic clamp technique. Whole-body skeletal muscle mass and visceral adipose tissue were measured using a multi-slice magnetic resonance imaging protocol. Total body skeletal muscle mass was not associated with any measure of glucose metabolism in men or women (p > 0.10). These observations remained independent of age and total adiposity. Conversely, visceral adipose tissue was a significant predictor of various measures of glucose metabolism in both men and women with or without control for age and (or) total body fat (p < 0.05). Although skeletal muscle is a primary site for glucose uptake and deposition, these findings suggest that unlike visceral adipose tissue, whole-body skeletal muscle mass per se is not associated with either glucose tolerance or insulin sensitivity in overweight and obese men and women.

scholarly journals Role of patatin-like phospholipase domain-containing 3 gene for hepatic lipid content and insulin resistance in diabetes

2020 ◽  
Author(s):  
Oana P. Zaharia ◽  
Klaus Strassburger ◽  
Birgit Knebel ◽  
Yuliya Kupriyanova ◽  
Yanislava Karusheva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Lipid Content ◽  
Whole Body ◽  
Hepatic Lipid ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Glucose Tolerant ◽  
Hepatic Lipid Content

<a><b>Objective</b></a>: The rs738409(G) single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 (<i>PNPLA3</i>) gene associates with increased risk and progression of nonalcoholic fatty liver disease (NAFLD). As the recently-described severe insulin-resistant diabetes (SIRD) cluster specifically relates to NAFLD, this study examined whether this SNP differently associates with hepatic lipid content (HCL) and insulin sensitivity in recent-onset diabetes mellitus. <p><b>Research Design and Methods</b>: A total of 917 participants of the German Diabetes Study underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution and magnetic resonance spectroscopy. </p> <p><b>Results:</b> The G allele associated positively with HCL (β=0.36, p<0.01), independent of age, sex and BMI across the whole cohort, but not in the individual clusters. SIRD exhibited lowest whole-body insulin sensitivity compared to severe insulin-deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD) and severe autoimmune diabetes clusters (SAID; all p<0.001). Interestingly, SIRD presented with higher prevalence of the rs738409(G) SNP compared to other clusters and the glucose-tolerant control group (p<0.05). HCL was higher in SIRD [13.6 (5.8;19.1)%] compared to MOD [6.4 (2.1;12.4)%, p<0.05], MARD [3.0 (1.0;7.9)%, p<0.001], SAID [0.4 (0.0;1.5)%, p<0.001] and the glucose tolerant group [0.9 (0.4;4.9)%, p<0.001]. Although the <i>PNPLA3</i> polymorphism did not directly associate with whole-body insulin sensitivity in SIRD, the G allele carriers had higher circulating free fatty acid concentrations and greater adipose-tissue insulin resistance compared to non-carriers (both p<0.001).</p> <b>Conclusions:</b> Members of the severe insulin resistant diabetes cluster are more frequently carriers of the rs738409(G) variant. The SNP-associated adipose-tissue insulin resistance and excessive lipolysis may contribute to their NAFLD.

scholarly journals Effects of metformin on metabolism of white and brown adipose tissue in obese C57BL/6J mice

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Yuan ◽  
Juan Li ◽  
Wei-Gang Zhao ◽  
Wei Sun ◽  
Shuai-Nan Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Brown Adipose Tissue ◽  
Tolerance Test ◽  
Normal Diet ◽  
The Body ◽  
Oral Glucose ◽  
Obese Mice ◽  
Brown Adipose

Abstract Background To investigate effects of metformin on the regulation of proteins of white adipose tissue (WAT) and brown adipose tissue (BAT) in obesity and explore the underlying mechanisms on energy metabolism. Methods C57BL/6J mice were fed with normal diet (ND, n = 6) or high-fat diet (HFD, n = 12) for 22 weeks. HFD-induced obese mice were treated with metformin (MET, n = 6). After treatment for 8 weeks, oral glucose tolerance test (OGTT) and hyperinsulinemic–euglycemic clamp were performed to evaluate the improvement of glucose tolerance and insulin sensitivity. Protein expressions of WAT and BAT in mice among ND, HFD, and MET group were identified and quantified with isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC–MS/MS. The results were analyzed by MASCOT, Scaffold and IPA. Results The glucose infusion rate in MET group was increased significantly compared with HFD group. We identified 4388 and 3486 proteins in WAT and BAT, respectively. As compared MET to HFD, differential expressed proteins in WAT and BAT were mainly assigned to the pathways of EIF2 signaling and mitochondrial dysfunction, respectively. In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly. Conclusions Metformin improved the body weight and insulin sensitivity of obese mice. Meanwhile, metformin might ameliorate endoplasmic reticulum stress in WAT, and affect fatty acid metabolism in WAT and BAT. CPT1 might be a potential target of metformin in WAT and BAT.

scholarly journals Insulin Sensitivity and β-Cell Function in Protease Inhibitor-Treated and -Naive Human Immunodeficiency Virus-Infected Children

2005 ◽  
Vol 90 (1) ◽  
pp. 168-174 ◽  
Author(s):  
Ari Bitnun ◽  
Etienne Sochett ◽  
Paul T. Dick ◽  
Teresa To ◽  
Craig Jefferies ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Sensitivity Index ◽  
Insulin Sensitivity Index ◽  
Β Cell ◽  
The Mean ◽  
Visceral Adipose

Abstract Previous pediatric studies have failed to demonstrate a clear association between protease inhibitor (PI) therapy and abnormal glucose homeostasis in HIV-infected children. To define more precisely the impact of PI therapy on glucose homeostasis in this population, we performed the insulin-modified frequent-sampling iv glucose tolerance test on 33 PI-treated and 15 PI-naive HIV-infected children. Other investigations included fasting serum lipids; glucose, insulin, and C-peptide; single-slice abdominal computed tomography; and, in a subset of PI-treated children, an oral glucose tolerance test. There were no differences between the two groups with respect to fasting serum insulin or C-peptide, homeostatic model assessment insulin resistance, or quantitative insulin sensitivity check index. The mean insulin sensitivity index of PI-treated and PI-naive children was 6.93 ± 6.37 and 10.58 ± 12.93 × 10−4min−1 [μU/ml]−1, respectively (P = 0.17). The mean disposition index for the two groups was 1840 ± 1575 and 3708 ± 3005 × 10−4min−1 (P = 0.013), respectively. After adjusting for potential confounding variables using multiple regression analysis, the insulin sensitivity index and disposition index of PI-treated children were significantly lower than that of PI-naive children (P = 0.01 for both). In PI-treated but not PI-naive children, insulin sensitivity correlated inversely with visceral adipose tissue area (r = −0.43, P = 0.01) and visceral to sc adipose tissue ratio (r = −0.49, P = 0.004). Mildly impaired glucose tolerance was noted in four of 21 PI-treated subjects tested. Our results demonstrate not only that PI therapy reduces insulin sensitivity in HIV-infected children but also that it impairs the β-cell response to this reduction in insulin sensitivity and, in a subset of children, leads to the development of impaired glucose tolerance. The presence of insulin resistance, dyslipidemia, and the significant correlation of reduced insulin sensitivity with increased visceral adipose tissue content suggest that PI-containing highly active antiretroviral therapy is associated with the emergence of early features of a metabolic syndrome-like phenotype.

scholarly journals Sexually Dimorphic Diet-Induced Insulin Resistance in Obese Tissue Inhibitor of Metalloproteinase-2 (TIMP-2)-Deficient Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1300-1313 ◽  
Author(s):  
Diane M. Jaworski ◽  
Olga Sideleva ◽  
Holly M. Stradecki ◽  
Garret D. Langlois ◽  
Aida Habibovic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Mass ◽  
Wild Type ◽  
Β Cell ◽  
Tissue Inhibitor ◽  
Glucose Transporter 2

Abstract Circulating levels of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are altered in human obesity and may contribute to its pathology. TIMP-2 exerts MMP-dependent (MMP inhibition and pro-MMP-2 activation) and MMP-independent functions. To assess the role of TIMP-2 in a murine model of nutritionally induced obesity, weight gain in wild-type and TIMP-2 deficient [knockout (KO)] mice fed a chow or high-fat diet (HFD) was determined. The effects of diet on glucose tolerance and insulin sensitivity, as well as pancreatic β-cell and adipocyte physiology, were assessed. Chow-fed TIMP-2 KO mice of both sexes became obese but maintained relatively normal glucose tolerance and insulin sensitivity. Obesity was exacerbated on the HFD. However, HFD-fed male, but not female, TIMP-2 KO mice developed insulin resistance with reduced glucose transporter 2 and pancreatic and duodenal homeobox 1 levels, despite increased β-cell mass and hyperplasia. Thus, although β-cell mass was increased, HFD-fed male TIMP-2 KO mice develop diabetes likely due to β-cell exhaustion and failure. TIMP-2 mRNA, whose expression was greatest in sc adipose tissue, was down-regulated in HFD-fed wild-type males, but not females. Furthermore, HFD increased membrane type 1-MMP (MMP-14) expression and activity in male, but not female, sc adipose tissue. Strikingly, MMP-14 expression increased to a greater extent in TIMP-2 KO males and was associated with decreased adipocyte collagen. Taken together, these findings demonstrate a role for TIMP-2 in maintaining extracellular matrix integrity necessary for normal β-cell and adipocyte physiology and that loss of extracellular matrix integrity may underlie diabetic and obesogenic phenotypes.

scholarly journals Peroxiredoxin 6 Is a Key Antioxidant Enzyme in Modulating the Link between Glycemic and Lipogenic Metabolism

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Roberto Arriga ◽  
Francesca Pacifici ◽  
Barbara Capuani ◽  
Andrea Coppola ◽  
Augusto Orlandi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Serum Levels ◽  
Protective Role ◽  
Peroxiredoxin 6 ◽  
Food And Drink ◽  
Glucose Stimulated Insulin Secretion ◽  
Mice Liver

Insulin action and often glucose-stimulated insulin secretion are reduced in obesity. In addition, the excessive intake of lipids increases oxidative stress leading to overt type 2 diabetes mellitus (T2DM). Among the antioxidative defense systems, peroxiredoxin 6 (PRDX6) is able to reduce H2O2 and short chain and phospholipid hydroperoxides. Increasing evidences suggest that PRDX6 is involved in the pathogenesis of atherosclerosis and T2DM, but its role in the etiopathology of obesity and its complications is still not known. Therefore, in the present study, we sought to investigate this association by using PRDX6 knockout mice (PRDX6-/-). Metabolic parameters, like carbon dioxide (VCO2) production, oxygen consumption (VO2), and the respiratory exchange ratio (RER), were determined using metabolic cages. Intraperitoneal insulin and glucose tolerance tests were performed to evaluate insulin sensitivity and glucose tolerance, respectively. Liver and pancreas histochemical analyses were also evaluated. The expression of enzymes involved in lipid and glucose metabolism was analyzed by real-time PCR. Following 24 weeks of high-fat-diet (HFD), PRDX6-/- mice showed weight gain and higher food and drink intake compared to controls. VO2 consumption and VCO2 production decreased in PRDX6-/- mice, while the RER was lower than 0.7 indicating a prevalent lipid metabolism. PRDX6-/- mice fed with HFD showed a further deterioration on insulin sensitivity and glucose-stimulated insulin secretion. Furthermore, in PRDX6-/- mice, insulin did not suppress adipose tissue lipolysis with consequent hepatic lipid overload and higher serum levels of ALT, cholesterol, and triglycerides. Interestingly, in PRDX6-/- mice, liver and adipose tissue were associated with proinflammatory gene upregulation. Finally, PRDX6-/- mice showed a higher rate of nonalcoholic steatohepatitis (NASH) compared to control. Our results suggest that PRDX6 may have a functional and protective role in the development of obesity-related metabolic disorders such as liver diseases and T2DM and may be considered a potential therapeutic target against these illnesses.

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