Central activating transcription factor 4 (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve.

ABSTRACT: Recent studies have revealed that the central nervous system, particularly the hypothalamus, is critical for regulating insulin sensitivity in peripheral tissues. The aim of our current study is to investigate the possible involvement of hypothalamic activating transcription factor 4 (ATF4) in the regulation of insulin sensitivity in the liver. Here, we show that overexpression of ATF4 in the hypothalamus resulting from intracerebroventricular injection of adenovirus expressing ATF4 induces hepatic insulin resistance in mice and that inhibition of hypothalamic ATF4 by intracerebroventricular adenovirus expressing a dominant-negative ATF4 variant has the opposite effect. We also show that hypothalamic ATF4-induced insulin resistance is significantly blocked by selective hepatic vagotomy or

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC3712031 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature