Disruption of the Circadian Clock Component BMAL1 Elicits an Endocrine Adaption Impacting on Insulin Sensitivity and Liver Disease

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Mar 3

PMID 35238641

Authors

Celine Jouffe

Benjamin D Weger

Eva Martin

Florian Atger

Meltem Weger

Cedric Gobet

Divya Ramnath

Aline Charpagne

Delphine Morin-Rivron

Elizabeth E Powell

Matthew J Sweet

Mojgan Masoodi

N Henriette Uhlenhaut

Frederic Gachon

Affiliations

Soon will be listed here.

Abstract

SignificanceWhile increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), the involved mechanisms are still poorly described. Here, we show that, in both humans and mice, the pathogenesis of NAFLD is associated with the disruption of the circadian clock combined with perturbations of the growth hormone and sex hormone pathways. However, while this condition protects mice from the development of fibrosis and insulin resistance, it correlates with increased fibrosis in humans. This suggests that the perturbation of the circadian clock and its associated disruption of the growth hormone and sex hormone pathways are critical for the pathogenesis of metabolic and liver diseases.

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