Acute and selective inhibition of adipocyte glyceroneogenesis and cytosolic phosphoenolpyruvate carboxykinase by interferon γ

Interferon γ (IFN-γ) was previously shown to promote fatty acid (FA) release from adipose tissue (AT). Net lipolysis is an equilibrium between triglyceride breakdown and FA re-esterification. The latter requires activated glyceroneogenesis for glycerol-3-phosphate synthesis and increased cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), the key enzyme in this pathway. We wondered whether glyceroneogenesis and PEPCK-C would be IFN-γ targets. We injected mice with IFN-γ, and exposed either AT explants and isolated adipocytes from humans and mice or 3T3-F442A adipocytes to IFN-γ before monitoring expression of genes involved in lipid metabolism and the metabolic consequences. We show that IFN-γ induces a large increase in FA release without affecting glycerol output and decreases [1-14C]-pyruvate incorporation into lipids, thus demonstrating that FA re-esterification is reduced due to diminished glyceroneogenesis. A series of mRNA encoding proteins involved in FA metabolism remained unaffected by IFN-γ,...