title: Ostα-/- mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity.
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.
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York;
authors.forename: Sadie G
authors.initials: SG
authors.lastname: Wheeler
authors.forename: Christine L
authors.initials: CL
authors.lastname: Hammond
authors.forename: François R
authors.initials: FR
authors.lastname: Jornayvaz
authors.forename: Varman T
authors.initials: VT
authors.lastname: Samuel
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Soroka
authors.forename: James L
authors.initials: JL
authors.lastname: Boyer
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hinkle
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Ballatori
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D015430:Weight Gain / Q000235:genetics*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D026901:Membrane Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C476576:organic solute transporter alpha, mouse
keywords: bile acids; glucose tolerance; insulin sensitivity; lipid absorption; organic solute transporter