| First Author | Wheeler SG | Year | 2014 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 306 |
| Issue | 5 | Pages | G425-38 |
| PubMed ID | 24381083 | Mgi Jnum | J:210898 |
| Mgi Id | MGI:5572857 | Doi | 10.1152/ajpgi.00368.2013 |
| Citation | Wheeler SG, et al. (2014) Ostalpha-/- mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity. Am J Physiol Gastrointest Liver Physiol 306(5):G425-38 |
| abstractText | The organic solute transporter OSTalpha-OSTbeta 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. Ostalpha(-/-) mice exhibit reduced bile acid pools and impaired lipid absorption. In this study, wild-type and Ostalpha(-/-) mice were characterized at 5 and 12 mo of age. Ostalpha(-/-) mice were resistant to age-related weight gain, body fat accumulation, and liver and muscle lipid accumulation, and male Ostalpha(-/-) mice lived slightly longer than wild-type mice. Caloric intake and activity levels were similar for Ostalpha(-/-) and wild-type male mice. Fecal lipid excretion was increased in Ostalpha(-/-) 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 Ostalpha(-/-) animals. Hepatic expression of cholesterol synthetic genes was upregulated in Ostalpha(-/-) mice, showing that increased cholesterol synthesis partially compensated for reduced dietary cholesterol absorption. Glucose tolerance was improved in male Ostalpha(-/-) mice, and insulin sensitivity was improved in male and female Ostalpha(-/-) 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 Ostalpha(-/-) than wild-type mice. These findings indicate that loss of OSTalpha-OSTbeta protects against age-related weight gain and insulin resistance. |
