Fig. 2

Regulation of lipid metabolism by BAF60a and BAF60c in periportal and perivenous hepatocytes, respectively, under the control of nutritional and hormonal signals. In periportal (PP) hepatocytes, PGC-1α is deacetylated by SIRT1 and activates its activity during fasting. In this state, PGC-1α mediates the recruitment of BAF60a to PPARα-binding sites, to transcriptional activation of mitochondrial fat-oxidation genes, leading promoting the oxidation of fatty acids. The acetyl-CoA is produced by fatty acid oxidation and transported from mitochondria to cytoplasm. In perivenous (PV) hepatocytes, insulin-mediated activation of atypical PKCζ/λ via the PI3K pathway induces SREBP-1c expression. BAF60c recruits BAF subunits including BAF155, BAF190, and BAF250 for the formation of lipoBAF complex to activate lipogenic program. BAF60c is phosporylated by aPKC in response to feeding/insulin. Phosphorylated BAF60c translocates from the cytosol to the nucleus and directly interacts with phosphorylated/acetylated USF, thus allowing recruitment of lipoBAF and remodeling of chromatin to activate lipogenic genes. USF-1, which is phosphorylated by DNA-PK and then acetylated by P/CAF, recruits BAF60c. DNA-PK is activated by PP1. USF-1 bound to the -65 E-box recruits SREBP-1c to bind the nearby SRE during feeding/insulin. The closely spaced arrangement of the E-box and SRE in many lipogenic promoters may allow USF-1 and SREBP-1c to cooperatively activate lipogenic genes transcription, leading to increased in the expression of ATP citrate lyase (ACL), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), to facilitate the synthesis of fatty acids. Moreover, PGC-1α is acetylated by GCN5 resulting in a transcriptionally inactive protein in response to feeding/insulin. Since fatty acid oxidation occur mainly in PV hepatocyte, whereas lipogenesis occur predominantly in PP hepatocyte. Therefore, the acetyl-CoA in PP hepatocyte is transported into PV hepatocyte and used for fatty acid synthesis, whereas the fatty acid in PV hepatocyte is shifted to PP hepatocyte and oxidated to acetyl-CoA