Ostα−/− mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity
| Autor: | Sadie G. Wheeler, Christine L. Hammond, Gerald I. Shulman, Carol J. Soroka, Varman T. Samuel, François R Jornayvaz, Nazzareno Ballatori, James L. Boyer, Patricia M. Hinkle |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Aging Physiology medicine.medical_treatment Body Composition/genetics/physiology Insulin Resistance/genetics Adipose tissue Receptors Cytoplasmic and Nuclear Weight Gain chemistry.chemical_compound Mice Mice Knockout Bile acid Intestinal lipid absorption Gastroenterology Liver and Biliary Tract Adipose Tissue Adipose Tissue/physiology Body Composition Receptors Cytoplasmic and Nuclear/genetics/physiology Female medicine.medical_specialty medicine.drug_class Dietary lipid Bile Acids and Salts/metabolism Lipid Metabolism/genetics/physiology Biology Weight Gain/genetics Bile Acids and Salts Insulin resistance Physiology (medical) Internal medicine medicine Animals Membrane Transport Proteins/genetics/metabolism Hepatology Gene Expression Regulation/physiology Cholesterol Insulin Membrane Transport Proteins Lipid metabolism Biological Transport medicine.disease Lipid Metabolism Rats Endocrinology chemistry Gene Expression Regulation Insulin Resistance Aging/genetics/physiology |
| Zdroj: | American Journal of Physiology. Gastrointestinal and Liver Physiology, Vol. 306, No 5 (2014) pp. G425-438 |
| ISSN: | 0193-1857 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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