Brain-specific deletion of TRIM13 promotes metabolic stress-triggered insulin resistance, glucose intolerance, and neuroinflammation

2020 ◽  
Vol 527 (1) ◽  
pp. 138-145
Author(s):  
Yang Qian ◽  
Gao Lei ◽  
Liu Wen
Keyword(s):  
Insulin Resistance ◽  
Glucose Intolerance ◽  
Metabolic Stress ◽  
Specific Deletion

Overproduction of inter-α-trypsin inhibitor heavy chain 1 after loss of Gα13 in liver exacerbates systemic insulin resistance in mice

2019 ◽  
Vol 11 (513) ◽  
pp. eaan4735 ◽  
Author(s):  
Tae Hyun Kim ◽  
Ja Hyun Koo ◽  
Mi Jeong Heo ◽  
Chang Yeob Han ◽  
Yong-In Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Intolerance ◽  
Heavy Chain ◽  
Trypsin Inhibitor ◽  
Metabolic Stress ◽  
Whole Body ◽  
Secretory Proteins ◽  
Systemic Insulin Resistance ◽  
Glcnac Transferase ◽  
The Impact

The impact of liver disease on whole-body glucose homeostasis is largely attributed to dysregulated release of secretory proteins in response to metabolic stress. The molecular cues linking liver to whole-body glucose metabolism remain elusive. We found that expression of G protein α-13 (Gα13) was decreased in the liver of mice and humans with diabetes. Liver-specific deletion of the Gna13 gene in mice resulted in systemic glucose intolerance. Comparative secretome analysis identified inter-α-trypsin inhibitor heavy chain 1 (ITIH1) as a protein secreted by liver that was responsible for systemic insulin resistance in Gna13-deficient mice. Liver expression of ITIH1 positively correlated with surrogate markers for diabetes in patients with impaired glucose tolerance or overt diabetes. Mechanistically, a decrease in hepatic Gα13 caused ITIH1 oversecretion by liver through induction of O-GlcNAc transferase expression, facilitating ITIH1 deposition on the hyaluronan surrounding mouse adipose tissue and skeletal muscle. Neutralization of secreted ITIH1 ameliorated glucose intolerance in obese mice. Our findings demonstrate systemic insulin resistance in mice resulting from liver-secreted ITIH1 downstream of Gα13 and its reversal by ITIH1 neutralization.

Female 5[beta]-reductase knockout mice are protected from diet induced obesity, insulin resistance and glucose intolerance

2016 ◽  
Author(s):  
Laura Gathercole ◽  
Matthew Chapman ◽  
Dean Larner ◽  
Petra Klusonova ◽  
Trevor Penning ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Intolerance ◽  
Knockout Mice ◽  
Diet Induced Obesity

Diet quality and periodontal disease: Results from the oral infections, glucose intolerance and insulin resistance study (ORIGINS)

2021 ◽  
Vol 48 (5) ◽  
pp. 638-647
Author(s):  
Francesco DeMayo ◽  
Rebecca Molinsky ◽  
Muna J. Tahir ◽  
Sumith Roy ◽  
Jeanine M. Genkinger ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Periodontal Disease ◽  
Glucose Intolerance ◽  
Diet Quality ◽  
Oral Infections

scholarly journals Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5826-5834 ◽  
Author(s):  
Shoshana Yakar ◽  
Nomeli P. Nunez ◽  
Patricia Pennisi ◽  
Pnina Brodt ◽  
Hui Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tumor Growth ◽  
Glucose Intolerance ◽  
Tumor Development ◽  
Tumor Growth Rate ◽  
Obese Mice ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Body Adiposity ◽  
Obese Female

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.

scholarly journals Hepatic Bax Inhibitor-1 Inhibits IRE1α and Protects from Obesity-associated Insulin Resistance and Glucose Intolerance

2009 ◽  
Vol 285 (9) ◽  
pp. 6198-6207 ◽  
Author(s):  
Béatrice Bailly-Maitre ◽  
Bengt F. Belgardt ◽  
Sabine D. Jordan ◽  
Beatrice Coornaert ◽  
Miriam John von Freyend ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Intolerance

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.

Sign in / Sign up

Export Citation Format

Share Document