scholarly journals Telmisartan Improves Insulin Resistance and Modulates Adipose Tissue Macrophage Polarization in High-Fat-Fed Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1789-1799 ◽  
Author(s):  
Shiho Fujisaka ◽  
Isao Usui ◽  
Yukiko Kanatani ◽  
Masashi Ikutani ◽  
Ichiro Takasaki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Macrophage Polarization ◽  
High Fat ◽  
Adipose Tissues ◽  
Tissue Macrophage ◽  
Adipose Tissue Macrophage ◽  
Visceral Adipose

Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.

scholarly journals Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance

2015 ◽  
Vol 21 (3) ◽  
pp. 403-416 ◽  
Author(s):  
Michael J. Kraakman ◽  
Helene L. Kammoun ◽  
Tamara L. Allen ◽  
Virginie Deswaerte ◽  
Darren C. Henstridge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Tissue Macrophage ◽  
Macrophage Recruitment ◽  
Adipose Tissue Macrophage ◽  
Improve Insulin Resistance

scholarly journals Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue

2015 ◽  
Vol 112 (14) ◽  
pp. 4363-4368 ◽  
Author(s):  
James E. N. Minchin ◽  
Ingrid Dahlman ◽  
Christopher J. Harvey ◽  
Niklas Mejhert ◽  
Manvendra K. Singh ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Body Fat ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
High Fat ◽  
Type V ◽  
Visceral Adipose

Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown. Here we use in vivo imaging and genetic analysis in zebrafish to show that Plxnd1 regulates body fat distribution and insulin sensitivity. Plxnd1 deficiency in zebrafish induced hyperplastic morphology in visceral adipose tissue (VAT) and reduced lipid storage. In contrast, subcutaneous adipose tissue (SAT) growth and morphology were unaffected, resulting in altered body fat distribution and a reduced VAT:SAT ratio in zebrafish. A VAT-specific role for Plxnd1 appeared conserved in humans, as PLXND1 mRNA was positively associated with hypertrophic morphology in VAT, but not SAT. In zebrafish plxnd1 mutants, the effect on VAT morphology and body fat distribution was dependent on induction of the extracellular matrix protein collagen type V alpha 1 (col5a1). Furthermore, after high-fat feeding, zebrafish plxnd1 mutant VAT was resistant to expansion, and excess lipid was disproportionately deposited in SAT, leading to an even greater exacerbation of altered body fat distribution. Plxnd1-deficient zebrafish were protected from high-fat-diet-induced insulin resistance, and human VAT PLXND1 mRNA was positively associated with type 2 diabetes, suggesting a conserved role for PLXND1 in insulin sensitivity. Together, our findings identify Plxnd1 as a novel regulator of VAT growth, body fat distribution, and insulin sensitivity in both zebrafish and humans.

scholarly journals The role of GM-CSF in adipose tissue inflammation

2008 ◽  
Vol 295 (5) ◽  
pp. E1038-E1046 ◽  
Author(s):  
Dong-Hoon Kim ◽  
Darleen Sandoval ◽  
Jacquelyn A. Reed ◽  
Emily K. Matter ◽  
Emeline G. Tolod ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Knockout Mice ◽  
Wild Type ◽  
Tissue Macrophage ◽  
Gm Csf ◽  
Adipose Tissue Macrophage ◽  
Mesenteric Fat

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine that has a central action to reduce food intake and body weight. Consistent with this, GM-CSF knockout mice are more obese and hyperphagic than wild-type mice. However, in lung, GM-CSF is an important determinant of macrophage infiltration. Consequently, we sought to determine if GM-CSF might contribute to adipose tissue macrophage accumulation, insulin resistance, and low-grade inflammation that occurs when animals gain weight on a high-fat diet (HFD). We therefore determined how targeted genetic disruption of GM-CSF can affect adipose tissue macrophage and cytokine gene expression as well as glucose homeostasis by performing hyperinsulinemic-euglycemic clamps. The number of macrophages and CCR2 gene expression in adipose tissue of GM-CSF knockout mice was decreased relative to those in wild-type mice, and the adipocyte size of mesenteric fat was increased in GM-CSF knockout mice on a HFD compared with wild-type mice. The level of mRNA of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, and macrophage inflammatory protein-1α was significantly lower in mesenteric fat of GM-CSF knockout mice on the HFD than in wild-type mice. Using the hyperinsulinemic-euglycemic clamp technique, GM-CSF knockout mice had greater overall insulin sensitivity. This increase was due to enhanced peripheral uptake and utilization of glucose rather than to increased hepatic insulin sensitivity. Collectively, the data suggest that the GM-CSF knockout mutation ameliorates peripheral insulin resistance in spite of increased adiposity by reducing inflammation in adipose tissue in response to a HFD.

scholarly journals Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance

2016 ◽  
Vol 23 (3) ◽  
pp. 563 ◽  
Author(s):  
Michael J. Kraakman ◽  
Helene L. Kammoun ◽  
Tamara L. Allen ◽  
Virginie Deswaerte ◽  
Darren C. Henstridge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Tissue Macrophage ◽  
Macrophage Recruitment ◽  
Adipose Tissue Macrophage ◽  
Improve Insulin Resistance

Maraviroc ameliorates the increased adipose tissue macrophage recruitment induced by a high-fat diet in a mouse model of obesity

2016 ◽  
Vol 22 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Patricia Pérez-Matute ◽  
José G Pichel ◽  
María Iñiguez ◽  
Emma Recio-Fernández ◽  
Laura Pérez-Martínez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mouse Model ◽  
High Fat Diet ◽  
High Fat ◽  
Tissue Macrophage ◽  
Macrophage Recruitment ◽  
Adipose Tissue Macrophage

scholarly journals Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2109-2117 ◽  
Author(s):  
Elodie Riant ◽  
Aurélie Waget ◽  
Haude Cogo ◽  
Jean-François Arnal ◽  
Rémy Burcelin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Normal Chow ◽  
Visceral Adipose ◽  
Deficient Mice ◽  
Normal Chow Diet

Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17β-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERα-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-α) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERα-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERα pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.

scholarly journals Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice

2007 ◽  
Vol 117 (10) ◽  
pp. 2877-2888 ◽  
Author(s):  
Takashi Nomiyama ◽  
Diego Perez-Tilve ◽  
Daisuke Ogawa ◽  
Florence Gizard ◽  
Yue Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Macrophage Infiltration ◽  
Tissue Macrophage ◽  
Adipose Tissue Macrophage

scholarly journals Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats

2012 ◽  
Vol 108 (8) ◽  
pp. 1511-1518 ◽  
Author(s):  
Jéferson F. Goularte ◽  
Maria B. C. Ferreira ◽  
Gilberto L. Sanvitto
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Physical Exercise ◽  
Energy Intake ◽  
Liver Weight ◽  
Cafeteria Diet ◽  
Chow Diet ◽  
Diet Induced Obesity ◽  
Visceral Adipose

Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.

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