Adipocyte-specific Nos2 deletion improves insulin resistance and dyslipidemia through brown fat activation in diet-induced obese mice

Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice.

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Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

Food & Function ◽

10.1039/d1fo01394g ◽

2021 ◽

Author(s):

Haizhao Song ◽

Xinchun Shen ◽

Yang Zhou ◽

Xiaodong Zheng

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Gut Microbiota ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Liver Steatosis ◽

Obese Mice ◽

Black Rice ◽

High Fat ◽

Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

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332-OR: Pharmacological Inhibition of CREBZF Improves Insulin Resistance by Altering Activation of Macrophage in Adipose Tissue of Diet-Induced Obese Mice

Diabetes ◽

10.2337/db21-332-or ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 332-OR

Author(s):

YUXIAO LIU ◽

ZHIMIN HU ◽

ZHENGSHUAI LIU ◽

WEITONG SU ◽

ZENGPENG ZHENG ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Obese Mice ◽

Pharmacological Inhibition

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Transthyretin contributes to insulin resistance and diminishes exercise-induced insulin sensitivity in obese mice by inhibiting AMPK activity in skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00495.2020 ◽

2021 ◽

Author(s):

Yingzi He ◽

Ruojun Qiu ◽

Beibei Wu ◽

Weiwei Gui ◽

Xihua Lin ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Inhibitory Effect ◽

Quadriceps Femoris ◽

Treadmill Training ◽

C2c12 Cells ◽

Obese Mice ◽

Insulin Resistant ◽

Ampk Activity ◽

Exercise Induced

Exercise improves obesity-induced insulin resistance and metabolic disorders via mechanisms that remain unclear. Here, we show that the levels of the hepatokine transthyretin (TTR) in circulation are elevated in insulin-resistant individuals including high-fat diet (HFD)-induced obese mice, db/db mice, and patients with metabolic syndrome. Liver Ttr mRNA and circulating TTR levels were reduced in mice by treadmill training, as was the TTR levels in quadriceps femoris muscle; however, AMPK signalling activity was enhanced. Transgenic overexpression of TTR or injection of purified TTR triggered insulin resistance in mice fed on regular chow (RC). Furthermore, TTR overexpression reduced the beneficial effects of exercise on insulin sensitivity in HFD-fed mice. TTR was internalized by muscle cells via the membrane receptor Grp78 and the internalization into the quadriceps femoris was reduced by treadmill training. The TTR/Grp78 combination in C2C12 cells was increased, whereas the AMPK activity of C2C12 cells was decreased as the TTR concentration rose. Additionally, Grp78 silencing prevented the TTR internalization and reversed its inhibitory effect on AMPK activity in C2C12 cells. Our study suggests that elevated circulating TTR may contribute to insulin resistance and counteract the exercise-induced insulin sensitivity improvement; the TTR suppression might be an adaptive response to exercise through enhancing AMPK activity in skeletal muscles.

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Linseed oil improves hepatic insulin resistance in obese mice through modulating mitochondrial quality control

Journal of Functional Foods ◽

10.1016/j.jff.2018.12.016 ◽

2019 ◽

Vol 53 ◽

pp. 166-175 ◽

Cited By ~ 2

Author(s):

Xiao Yu ◽

Shasha Huang ◽

Qianchun Deng ◽

Yuhan Tang ◽

Ping Yao ◽

...

Keyword(s):

Insulin Resistance ◽

Quality Control ◽

Linseed Oil ◽

Hepatic Insulin Resistance ◽

Obese Mice ◽

Mitochondrial Quality Control

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Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice

PPAR Research ◽

10.1155/2018/4292509 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Sorim Choung ◽

Kyong Hye Joung ◽

Bo Ram You ◽

Sang Ki Park ◽

Hyun Jin Kim ◽

...

Keyword(s):

Insulin Resistance ◽

Hepatic Steatosis ◽

Plasma Cholesterol ◽

Cholesterol Biosynthesis ◽

Peroxisome Proliferator ◽

Obese Mice ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Expression ◽

Expression Of Genes

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid β-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPARγ and phosphorylated PPARγ at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPARα and diminished levels of PPARγ phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPARα and posttranslational modification of PPARγ in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.

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