Fig. 3

Overview of sirtuins in lipid metabolism. Selected pathways in nucleus, cytosol and mitochondria are depicted. a Activating LCAD, a key enzyme in long-chain fatty acids oxidation, SIRT3 increases β-oxidation in hepatocytes and skeletal muscle. Both SIRT3 and SIRT5 promotes ketogenesis via HMGCS2 in liver. In cytoplasm, SIRT2 deacetylates ACLY and deters lipid synthesis. In contrast to SIRT3, SIRT4 inhibits MCD and contributes to increased malonyl CoA,which suppresses the fatty acid translocator CAT-1 and shuts down entery of fatty acid for β-oxidation. b SIRT1 and SIRT6 reduce the activity of nuclear hormone receptor PPARγand lead to decreased adipogenesis. SIRT1 also destabilizes SREBP1 and transcriptionally represses lipogenesis. Besides the negative regulation, SIRT1 boosts fatty acid oxidation by enhancing PPARα and its coactivator PGC1α. LCAD, long chain acyl CoA dehydrogenase; HMGCS2,3-hydroxy-3-methylglutaryl CoA synthase 2; ACLY,ATP citrate lyase; MCD,malonyl CoA decarboxylase; CAT-1,carnitine acyl transferase-1; SREBP1,sterol regulatory element binding protein 1