期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 306, 期 5, 页码 G425-G438出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00368.2013
关键词
bile acids; glucose tolerance; insulin sensitivity; lipid absorption; organic solute transporter
资金
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-067214, DK-19974]
- National Institute of Environmental Health Sciences Training Grant [ES-070236]
- Center Grant [ES-01247]
- NIDDK [DK-40936, U24 DK-076169, DK-25636, DK-34989]
- Veterans Health Administration Biomedical Laboratory Research and Development [I01 BX000901]
The organic solute transporter OST alpha-OST beta 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. Ost alpha(-/-) mice exhibit reduced bile acid pools and impaired lipid absorption. In this study, wild-type and Ost alpha(-/-) mice were characterized at 5 and 12 mo of age. Ost alpha(-/-) mice were resistant to age-related weight gain, body fat accumulation, and liver and muscle lipid accumulation, and male Ost alpha(-/-) mice lived slightly longer than wild-type mice. Caloric intake and activity levels were similar for Ost alpha(-/-) and wild-type male mice. Fecal lipid excretion was increased in Ost alpha(-/-) 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 Ost alpha(-/-) animals. Hepatic expression of cholesterol synthetic genes was upregulated in Ost alpha(-/-) mice, showing that increased cholesterol synthesis partially compensated for reduced dietary cholesterol absorption. Glucose tolerance was improved in male Ost alpha(-/-) mice, and insulin sensitivity was improved in male and female Ost alpha(-/-) 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 Ost alpha(-/-) than wild-type mice. These findings indicate that loss of OST alpha-OST beta protects against age-related weight gain and insulin resistance.
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