Chronic circadian shift leads to adipose tissue inflammation and fibrosis

Details

• Alternative Title:
  Mol Cell Endocrinol
• Personal Author:
  Xiong, Xuekai ; Lin, Yayu ; Lee, Jeongkyung ; Paul, Antonio ; Yechoor, Vijay ; Figueiro, Mariana ; Ma, Ke
• Description:
  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.
• Subjects:
  Adipocytes Adipogenesis Adipose Tissue Animals Article Circadian Clock Circadian Clocks Down-Regulation Fibrosis Gene Expression Profiling Gene Expression Regulation Gene Ontology Inflammation Insulin Resistance Macrophages Male Mice Mice, Inbred C57BL Neovascularization, Pathologic Photoperiod Shiftwork Signal Transduction TOR Serine-Threonine Kinases Transcriptome Up-Regulation

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• Source:
  Mol Cell Endocrinol. 521:111110
• Pubmed ID:
  33285245
• Pubmed Central ID:
  PMC7799174
• Document Type:
  Journal Article
• Funding:
  R01 DK097160/DK/NIDDK NIH HHSUnited States/ ; R01 DK112794/DK/NIDDK NIH HHSUnited States/ ; R01 OH010668/OH/NIOSH CDC HHSUnited States/ ; R01OH010668/ACL/ACL HHSUnited States/
• Volume:
  521
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b8c9db1fd30563eaa6407df5c08a6ed2137f9fcdec1e3b5517383bad3392a9c8
• Download URL:
  https://stacks.cdc.gov/view/cdc/100404/cdc_100404_DS1.pdf
• File Type:
  [PDF - 2.61 MB ]