Ostα-/- mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity.

Details

Serval ID
serval:BIB_1A607B7DBDFF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Ostα-/- mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity.
Journal
American Journal of Physiology. Gastrointestinal and Liver Physiology
Author(s)
Wheeler S.G., Hammond C.L., Jornayvaz F.R., Samuel V.T., Shulman G.I., Soroka C.J., Boyer J.L., Hinkle P.M., Ballatori N.
ISSN
1522-1547 (Electronic)
ISSN-L
0193-1857
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
306
Number
5
Pages
G425-G438
Language
english
Abstract
The organic solute transporter OSTα-OSTβ is a key transporter for the efflux of bile acids across the basolateral membrane of ileocytes and the subsequent return of bile acids to the liver. Ostα(-/-) mice exhibit reduced bile acid pools and impaired lipid absorption. In this study, wild-type and Ostα(-/-) mice were characterized at 5 and 12 mo of age. Ostα(-/-) mice were resistant to age-related weight gain, body fat accumulation, and liver and muscle lipid accumulation, and male Ostα(-/-) mice lived slightly longer than wild-type mice. Caloric intake and activity levels were similar for Ostα(-/-) and wild-type male mice. Fecal lipid excretion was increased in Ostα(-/-) mice, indicating that a defect in lipid absorption contributes to decreased fat accumulation. Analysis of genes involved in intestinal lipid absorption revealed changes consistent with decreased dietary lipid absorption in Ostα(-/-) animals. Hepatic expression of cholesterol synthetic genes was upregulated in Ostα(-/-) mice, showing that increased cholesterol synthesis partially compensated for reduced dietary cholesterol absorption. Glucose tolerance was improved in male Ostα(-/-) mice, and insulin sensitivity was improved in male and female Ostα(-/-) mice. Akt phosphorylation was measured in liver and muscle tissue from mice after acute administration of insulin. Insulin responses were significantly larger in male and female Ostα(-/-) than wild-type mice. These findings indicate that loss of OSTα-OSTβ protects against age-related weight gain and insulin resistance.
Keywords
Adipose Tissue/physiology, Aging/genetics, Aging/physiology, Animals, Bile Acids and Salts/metabolism, Biological Transport, Body Composition/genetics, Body Composition/physiology, Female, Gene Expression Regulation/physiology, Insulin Resistance/genetics, Lipid Metabolism/genetics, Lipid Metabolism/physiology, Male, Membrane Transport Proteins/genetics, Membrane Transport Proteins/metabolism, Mice, Mice, Knockout, Rats, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/physiology, Weight Gain/genetics
Pubmed
Web of science
Create date
10/09/2015 12:00
Last modification date
20/08/2019 12:51
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