Medicine and Health Sciences Commons^™

Sirt1 Deacetylates And Inhibits Srebp-1c Activity In Regulation Of Hepatic Lipid Metabolism, Bhaskar Ponugoti, Dong-Hyun Kim, Zhen Xiao, Zachary Smith, Ji Miao, Mengwei Zang, Shwu-Yuan Wu, Cheng-Ming Chiang, Timothy D. Veenstra, Jongsook Kim Kemper

Pharmaceutical Sciences Faculty Publications

The SIRT1 deacetylase inhibits fat synthesis and stimulates fat oxidation in response to fasting, but the underlying mechanisms remain unclear. Here we report that SREBP-1c, a key lipogenic activator, is an in vivo target of SIRT1. SIRT1 interaction with SREBP-1c was increased during fasting and decreased upon feeding, and consistently, SREBP-1c acetylation levels were decreased during fasting in mouse liver. Acetylated SREBP-1c levels were also increased in HepG2 cells treated with insulin and glucose to mimic feeding conditions, and down-regulation of p300 by siRNA decreased the acetylation. Depletion of hepatic SIRT1 by adenoviral siRNA increased acetylation of SREBP-1c with increased …