Nr2e1 deficiency aggravates insulin resistance and chronic inflammation of visceral adipose tissues in a diet-induced obese mice model

Life Sciences ◽  
2021 ◽  
Vol 278 ◽  
pp. 119562
Author(s):  
Guangzhen He ◽  
Jiaowei Gu ◽  
Huawei Wang ◽  
Siyuan Cheng ◽  
Qing Xiong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chronic Inflammation ◽  
Obese Mice ◽  
Mice Model ◽  
Adipose Tissues ◽  
Visceral Adipose

scholarly journals Dietary glycemic index and dietary glycemic load is associated with apelin gene expression in visceral and subcutaneous adipose tissues of adults

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Emad Yuzbashian ◽  
Golaleh Asghari ◽  
Maryam Aghayan ◽  
Mehdi Hedayati ◽  
Maryam Zarkesh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Glycemic Index ◽  
Glycemic Load ◽  
Carbohydrate Intake ◽  
Model Assessment ◽  
Total Carbohydrate ◽  
Adipose Tissues ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Abstract Background Apelin, as an adipokine, plays an important role in the pathogenesis of insulin resistance and type 2 diabetes. This study aimed to determine whether the quality and quantity of dietary carbohydrates were associated with apelin gene expression in subcutaneous and visceral adipose tissues. Methods In this cross-sectional study, 102 adults who underwent minor abdominal surgery were selected. Approximately 100 mg of subcutaneous and visceral adipose tissues were collected during the surgery to measure apelin gene expression. Anthropometric measurment, blood samples, and dietary intakes were collected before surgery. The dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) were determined. Results The average apelin concentration was 269.6 ± 98.5(pg/mL), and 16.3% of participants were insulin resistant. There was a correlation between insulin (p-value = 0.043), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)(p-value = 0.045) and apelin gene expression in visceral adipose tissue. There was a positive association of apelin gene expression with dietary GI and GL after adjustment for age, sex, and waist circumference in visceral and subcutaneous adipose tissues(p < 0.05). Apelin gene expression in visceral(p = 0.002) and subcutaneous(p = 0.003) adipose tissues was directly associated with foods with a higher GI. There was no association between total carbohydrate intake and apelin gene expression in both visceral and subcutaneous adipose tissues. Conclusions Dietary GI and GL, not total carbohydrate intake, were positively associated with apelin gene expression in both visceral and subcutaneous adipose tissues. Future studies are warranted to illustrate the chronic and acute effect of carbohydrate quality on apelin homeostasis.

scholarly journals Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

2019 ◽  
Vol 7 (1) ◽  
pp. e000783 ◽  
Author(s):  
Liang Xu ◽  
Naoto Nagata ◽  
Guanliang Chen ◽  
Mayumi Nagashimada ◽  
Fen Zhuge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Chronic Inflammation ◽  
Plasma Levels ◽  
High Fat Diet ◽  
Macrophage Activation ◽  
Low Grade ◽  
Obese Mice ◽  
High Fat

ObjectiveWe reported previously that empagliflozin—a sodium-glucose cotransporter (SGLT) 2 inhibitor—exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice.Research design and methodsAfter 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin.ResultsTreatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation.ConclusionsTreatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.

scholarly journals Adipocyte Specific HO-1 Gene Therapy Is Effective in Antioxidant Treatment of Insulin Resistance and Vascular Function in an Obese Mice Model

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 40 ◽  
Author(s):  
Shailendra P. Singh ◽  
Menachem Greenberg ◽  
Yosef Glick ◽  
Lars Bellner ◽  
Gaia Favero ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gene Therapy ◽  
Adipose Tissue ◽  
Vascular Function ◽  
Therapeutic Approach ◽  
Vascular Dysfunction ◽  
Cellular Respiration ◽  
Heme Oxygenase 1 ◽  
Obese Mice ◽  
Mice Model

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity.

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 A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice

2014 ◽  
Vol 20 (8) ◽  
pp. 942-947 ◽  
Author(s):  
Da Young Oh ◽  
Evelyn Walenta ◽  
Taro E Akiyama ◽  
William S Lagakos ◽  
Denise Lackey ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chronic Inflammation ◽  
Obese Mice ◽  
Selective Agonist

scholarly journals Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Chelsea Hepler ◽  
Mengle Shao ◽  
Jonathan Y Xia ◽  
Alexandra L Ghaben ◽  
Mackenzie J Pearson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Significant Risk ◽  
Obese Mice ◽  
White Adipocyte ◽  
Genetic Ablation ◽  
Subcutaneous White Adipose Tissue ◽  
Novel Strategy ◽  
Thermogenic Adipocytes ◽  
Visceral Adipose ◽  
Transcriptional Suppressor

Visceral adiposity confers significant risk for developing metabolic disease in obesity whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective. Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic phenotype characterized by the accumulation of Ucp1+ beige/BRITE adipocytes (termed ‘browning’). In this study, we investigated the physiological consequences of browning murine visceral WAT by selective genetic ablation of Zfp423, a transcriptional suppressor of the adipocyte thermogenic program. Zfp423 deletion in fetal visceral adipose precursors (Zfp423loxP/loxP; Wt1-Cre), or adult visceral white adipose precursors (PdgfrbrtTA; TRE-Cre; Zfp423loxP/loxP), results in the accumulation of beige-like thermogenic adipocytes within multiple visceral adipose depots. Thermogenic visceral WAT improves cold tolerance and prevents and reverses insulin resistance in obesity. These data indicate that beneficial visceral WAT browning can be engineered by directing visceral white adipocyte precursors to a thermogenic adipocyte fate, and suggest a novel strategy to combat insulin resistance in obesity.

scholarly journals Amaranth Protein Improves Lipid Profile and Insulin Resistance in a Diet-induced Obese Mice Model

2017 ◽  
Vol 5 (12) ◽  
pp. 914-924 ◽  
Author(s):  
Abraham Escobedo-Moratilla ◽  
Aida J. Velarde-Salcedo ◽  
Cynthia V. Magaña-Hernández ◽  
Alberto Barrera-Pacheco ◽  
Eduardo Espitia-Rangel ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Profile ◽  
Obese Mice ◽  
Mice Model

scholarly journals Anti-inflammatory effect of piperine ameliorates insulin resistance in monosodium glutamate–treated obese mice

2020 ◽  
Author(s):  
Chaolong Liu ◽  
Yanting Yuan ◽  
Ji Zhou ◽  
Ruixin Hu ◽  
Lixia Ji ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Inflammatory Cytokines ◽  
Monosodium Glutamate ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Obese Mice ◽  
Adipose Tissues ◽  
Metabolic Inflammation ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background : Metabolic inflammation has been considered as an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M 1 -like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has been proven to have excellent anti-inflammatory activity and has therapeutic effects on a variety of inflammatory diseases. Therefore, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods: In this study, the monosodium glutamate (MSG) obese mice model was used. The 6-month-old MSG mice were divided into three groups, which were treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for successive 10 weeks, respectively. Meanwhile, the 6-month-old normal mice without MSG treatment were selected as normal controls. Results: When the obesity model was successfully established, obesity degree, insulin resistance, fasting blood glucose(FBG) and serum lipid profiles were significantly increased. Our results showed that the 10-week administration of piperine (40 mg/kg/d) not only significantly decreased the elevated FBG, serum TC and TG levels, but also enhanced infusion rate in hyperglycemic clamp experiment and improved the oral glucose intolerance as well as abnormal insulin tolerance in adult MSG obese mice. Additionally, piperine significantly decreased the total and differential white blood cell (WBC) count and the serum level of lipopolysaccharide (LPS), pro-inflammatory cytokines such as galectin-3 (Gal-3), interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M 1 -like polarization marker CD11c and Gal-3 in adipose tissues. In addition, the in vitro study showed that piperine inhibited LPS- stimulated polarization of RAW 264.7 cells toward the M 1 phenotype. Conclusions: In summary, these findings demonstrated that piperine could significantly inhibit body weight gain, reduce fat accumulation, rectify glycolipid metabolism disorders, improve severe insulin resistance and ameliorates systemic metabolic inflammation in MSG obesity mice. Our study indicates that piperine, as a potential natural alkaloid, can be used in the treatment of obesity-associated diabetes by delaying the progression of obesity-induced insulin resistance.

Abstract 1127: Natural-Killer T Cells are Involved in the Development of Glucose Intolerance and Microalbuminuria in Diet-Induced Obese Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kazue Ohmura ◽  
Naoki Ishimori ◽  
Yoshinori Ohmura ◽  
Satoshi Fujii ◽  
Yasuhiro Andoh ◽  
...  
Keyword(s):  
T Cells ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Natural Killer ◽  
Nkt Cells ◽  
Chow Diet ◽  
Obese Mice ◽  
Adipose Tissues ◽  
Visceral Adipose ◽  
Natural Killer T

Introduction: Natural killer T (NKT) cells are a unique subset of T lymphocytes, which recognize glycolipids and integrate inflammation producing pro-inflammatory cytokines on activation. We have demonstrated that NKT cells are present in atherosclerotic lesions and play a pivotal role in atherogenesis. NKT cells also reside in visceral adipose tissues, however, their pathogenic role has not been studied in metabolic derangements. Methods and Results: To determine whether NKT cells are involved in the development of metabolic phenotypes, male β 2 microglobulin knockout (KO) mice, which lack T cells and NKT cells, and C57BL/6J (WT) mice were fed an western diet (WD) containing 21% fat and 0.15% cholesterol or a chow diet for 13 weeks. In both KO (n=14) and WT (n=10) mice fed WD, visceral adipose-tissue weight, adipose cell size, and plasma leptin and non-HDL cholesterol levels were significantly increased compared to those fed a chow ( p< 0.05) but did not differ between KO and WT mice. However, in KO mice fed WD, impaired glucose tolerance (plasma glucose 15 minutes after intraperitoneal glucose injection, 228±7 vs 343±31 mg/dl, p< 0.001) and microalbuminuria (urine albumin/creatinin ratio, 10±1 vs 24±2 μg/mg, p< 0.0001) were significantly ameliorated, but not in WT mice. Plasma TNF-α was significantly lower in KO mice than in WT mice (29±6 vs 85±40 pg/ml, p< 0.05). Immunohistochemical staining of visceral adipose tissues revealed that F4/80 (+) macrophages in KO mice were markedly reduced to 34% of those in WT mice ( p< 0.0001). To further confirm that NKT cells can aggravate metabolic derangements, WT mice received α-galactosylceramide (0.1μg/g), which specifically activates NKT cells, (αgC, n=5) or saline (PBS, n=5) injection after 13 weeks of feeding WD. In αgC mice, impaired glucose tolerance (347±9 vs 308±13 mg/dl, p< 0.05) and microalbuminuria (35±8 vs 17±1 μg/mg, p< 0.05) were significantly exacerbated as compared to PBS mice. Conclusions: NKT cells enhance chronic inflammation in visceral adipose tissues and contribute to the development of metabolic derangements in diet-induced obese mice. NKT cells may be novel therapeutic targets in the prevention of metabolic syndrome.

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