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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: Wheeler, Sadie G; Hammond, Christine L; Jornayvaz, François R; Samuel, Varman T; Shulman, Gerald I; Soroka, Carol J; Boyer, James L; Hinkle, Patricia M; Ballatori, Nazzareno

Published In Am J Physiol Gastrointest Liver Physiol, (2014 Mar 01)

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.

PubMed ID: 24381083 Exiting the NIEHS site

MeSH Terms: 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*

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