Hepatic mTORC1 signaling activates ATF4 as part of its metabolic response to feeding and insulin.

ABSTRACT:

Objective

The mechanistic target of rapamycin complex 1 (mTORC1) is dynamically regulated by fasting and feeding cycles in the liver to promote protein and lipid synthesis while suppressing autophagy. However, beyond these functions, the metabolic response of the liver to feeding and insulin signaling orchestrated by mTORC1 remains poorly defined. Here, we determine whether ATF4, a stress responsive transcription factor recently found to be independently regulated by mTORC1 signaling in proliferating cells, is responsive to hepatic mTORC1 signaling to alter hepatocyte metabolism.

Methods

ATF4 protein levels and expression of canonical gene targets were analyzed in the liver following fasting and physiological feeding in the presence or absence of the mTORC1 inhibitor, rapamy

SUBMITTER: Byles V 

PROVIDER: S-EPMC8368025 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature