Fig. 1.
Hepatic Sirt6 knockout leads to elevated cholesterol levels and increased cholesterol biosynthetic gene expression. A, B: Serum and liver cholesterol measurements in 3-month-old control floxed (LoxpT6) and Sirt6 liver-specific knockout mice (LKOT6) (n = 10–12). C: Both cytoplasmic SREBP-2 precursor (Srebp2p) and nuclear mature SREBP-2 (nSrebp2) amounts were increased in the liver of LKOT6 mice, indicated by immunoblot analysis of total liver lysates and nuclear extracts, respectively. D: Sirt6 might not directly deacetylate SREBP-2 protein. nSrebp2 was cotransfected with GFP, Sirt1, or Sirt6 in HEK293 cells, and acetylation of SREBP-2 was analyzed by immunoprecipitation with anti-FLAG antibody followed by immunoblotting with anti-acetyl lysine antibody. E: Real-time PCR analysis of mRNAs for cholesterol metabolism genes in the liver of control floxed and LKOT6 mice (n = 3–5). F, G: SREBP-2 and its target genes were analyzed in the liver of control floxed and LKOT6 mice (n = 2–3) under overnight fasting or 4 h refeeding immediately after the fasting. Data are mean ± SEM; *P ≤ 0.05 by t-test. TC, total cholesterol.