Metformin inhibits hepatocellular glucose, lipid and cholesterol biosynthetic pathways by transcriptionally suppressing steroid receptor coactivator 2 (SRC-2).

ABSTRACT: The ability of the anti-diabetic drug metformin to inhibit anabolic processes including gluconeogenesis and lipogenesis is partly attributable to activation of the AMP-activated protein kinase (AMPK) pathway. The p160 steroid receptor coactivator 2 (SRC-2) is a key regulator of cellular metabolism and drives expression of the gluconeogenic enzyme glucose-6-phosphatase (G6Pc). Here, we uncovered a role for SRC-2 in the metabolic reprogramming imposed by metformin. In FaO cells, metformin dose-dependently reduced mRNA expression of SRC-2. Microarray analysis of metformin-treated cells revealed an overrepresentation of downregulated genes involved in biosynthesis of lipids and cholesterol. Several metformin-regulated genes including fatty acid synthase (FASN) were validated as transcriptional

SUBMITTER: Madsen A 

PROVIDER: S-EPMC4637908 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature