Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Nov 11

PMID 31706703

Citations 39

Authors

Fabiana Quagliarini

Ashfaq Ali Mir

Kinga Balazs

Michael Wierer

Kenneth Allen Dyar

Celine Jouffe

Konstantinos Makris

Johann Hawe

Matthias Heinig

Fabian Volker Filipp

Grant Daniel Barish

Nina Henriette Uhlenhaut

Affiliations

Soon will be listed here.

Abstract

The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.

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