Figure 4. Regulation of hepatic lipid homeostasis by HDAC3.

A. Gene Ontology analysis of the HDAC3 and Rev-erbα-bound genes that were upregulated in liver depleted of HDAC3 was performed as described in Methods. B. Oil Red O staining of liver from 12 week old HDAC3^fl/fl mice 2 weeks after tail vein injection of AAV-GFP or AAV-Cre. C. Hepatic triglyceride (TG) levels in mice treated as in “B”. D. Oil Red O staining of livers from 9 week old WT and mice lacking Rev-erbα (Rev-erbα KO). E. Hepatic TG levels in from livers from 9 week old WT and mice lacking Rev-erbα (Rev-erbα KO). Values are mean ± s.e.m. (n=4). *p<0.05 by student’s t-test. F. Hepatic de novo lipogenesis (DNL) in 12 week old HDAC3^fl/fl mice 1 week after infection with AAV-Cre or with AAV-GFP. Hepatic DNL is measured as newly synthesized ²H labeled palmitate. Values are mean ± s.e.m. (n=7–8). *p<0.05 by student’s t-test. G. Model depicting the mechanistic links between the daily cycles of Rev-erbα expression, HDAC3 genomic recruitment, epigenomic status, and hepatic lipogenesis.