Elsevier

Molecular Metabolism

Volume 2, Issue 4, November 2013, Pages 457-467
Molecular Metabolism

Original article
Cholesteryl ester transfer protein protects against insulin resistance in obese female mice

https://doi.org/10.1016/j.molmet.2013.08.007Get rights and content
Under a Creative Commons license
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Abstract

Cholesteryl ester transfer protein (CETP) shuttles lipids between lipoproteins, culminating in cholesteryl ester delivery to liver and increased secretion of cholesterol as bile. Since gut bile acids promote insulin sensitivity, we aimed to define if CETP improves insulin sensitivity with high-fat feeding. CETP and nontransgenic mice of both sexes became obese. Female but not male CETP mice had increased ileal bile acid levels versus nontransgenic littermates. CETP expression protected female mice from insulin resistance but had a minimal effect in males. In liver, female CETP mice showed activation of bile acid-sensitive pathways including Erk1/2 phosphorylation and Fxr and Shp gene expression. In muscle, CETP females showed increased glycolysis, increased mRNA for Dio2, and increased Akt phosphorylation, known effects of bile acid signaling. These results suggest that CETP can ameliorate insulin resistance associated with obesity in female mice, an effect that correlates with increased gut bile acids and known bile-signaling pathways.

Keywords

Insulin resistance
Obesity
Cholesterol
Bile
Glucose
Sex-differences

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