Chronic circadian shift leads to adipose tissue inflammation and fibrosis

Xuekai Xiong, Yayu Lin, Jeongkyung Lee, Antonio Paul, Vijay Yechoor, Mariana Figueiro, Ke Ma

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The circadian clock exerts temporal coordination of metabolic pathways. Clock disruption is intimately linked with the development of obesity and insulin resistance, and our previous studies found that the essential clock transcription activator, Brain and Muscle Arnt-like 1 (Bmal1), is a key regulator of adipogenesis. However, the metabolic consequences of chronic shiftwork on adipose tissues have not been clearly defined. Here, using an environmental lighting-induced clock disruption that mimics rotating shiftwork schedule, we show that chronic clock dysregulation for 6 months in mice resulted in striking adipocyte hypertrophy with adipose tissue inflammation and fibrosis. Both visceral and subcutaneous depots display enlarged adipocyte with prominent crown-like structures indicative of macrophage infiltration together with evidence of extracellular matrix remodeling. Global transcriptomic analyses of these fat depots revealed that shiftwork resulted in up-regulations of inflammatory, adipogenic and angiogenic pathways with disruption of normal time-of-the-day-dependent regulation. These changes in adipose tissues are associated with impaired insulin signaling in mice subjected to shiftwork, together with suppression of the mTOR signaling pathway. Taken together, our study identified the significant adipose depot dysfunctions induced by chronic shiftwork regimen that may underlie the link between circadian misalignment and insulin resistance.

Original languageEnglish
Article number111110
JournalMolecular and Cellular Endocrinology
Volume521
DOIs
StatePublished - 5 Feb 2021
Externally publishedYes

Keywords

  • Adipose tissue
  • Circadian clock
  • Inflammation
  • Insulin resistance
  • Shiftwork

Fingerprint

Dive into the research topics of 'Chronic circadian shift leads to adipose tissue inflammation and fibrosis'. Together they form a unique fingerprint.

Cite this