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

Nov 11, 2019Molecular cell

High-Fat Diet Changes Daily Gene Control of Stress Hormone Response

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Glucocorticoid receptor (GR) binding in mouse livers shows a rhythmic pattern that correlates with metabolic processes across the day-night cycle.

GR regulates metabolic processes through time-dependent control of target gene expression.
Differential regulation occurs for circulating glucose and triglycerides during feeding and fasting states.
Most oscillating genes are bound by GR, indicating its significant role in circadian rhythms.
High-fat diets alter the rhythmic pattern of gene expression without affecting GR's binding to DNA.
In obese mice, increased co-occupancy of the protein STAT5 with GR was observed, influencing gene expression.

AI simplified

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.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief