Ectopic lipid deposition mediates insulin resistance in adipose specific 11?-hydroxysteroid dehydrogenase type 1 transgenic mice.

ABSTRACT: CONTEXT:Excessive adipose glucocorticoid action is associated with insulin resistance, but the mechanisms linking adipose glucocorticoid action to insulin resistance are still debated. We hypothesized that insulin resistance from excess glucocorticoid action may be attributed in part to increased ectopic lipid deposition in liver. METHODS:We tested this hypothesis in the adipose specific 11?-hydroxysteroid dehydrogenase-1 (HSD11B1) transgenic mouse, an established model of adipose glucocorticoid excess. Tissue specific insulin action was assessed by hyperinsulinemic-euglycemic clamps, hepatic lipid content was measured, hepatic insulin signaling was assessed by immunoblotting. The role of hepatic lipid content was further probed by administration of the functionally liver-targeted mitochondrial uncoupler, Controlled Release Mitochondrial Protonophore (CRMP). FINDINGS:High fat diet fed HSD11B1 transgenic mice developed more severe hepatic insulin resistance than littermate controls (endogenous suppression of hepatic glucose production was reduced by 3.8-fold, P?

SUBMITTER: Abulizi A 

PROVIDER: S-EPMC6401251 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature