Chronic circadian shift leads to adipose tissue inflammation and fibrosis

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:521

Article

Xiong, Xuekai¹  Lin, Yayu¹  Lee, Jeongkyung²  Paul, Antonio³  Yechoor, Vijay²  Figueiro, Mariana^4,5  Ma, Ke¹ 

[1] City Hope Natl Med Ctr, Dept Diabet Complicat & Metab, Beckman Res Inst, Duarte, CA 91010 USA

[2] Univ Pittsburgh, Diabet & Beta Cell Biol Ctr, Dept Med, Div Endocrinol Diabet & Metab, Pittsburgh, PA 15213 USA

[3] Albany Med Coll, Dept Mol & Cellular Physiol, Albany, NY 12208 USA

[4] Rensselaer Polytech Inst, Lighting Res Ctr, Troy, NY 12180 USA

[5] Icahn Sch Med Mt Sinai, eDept Populat Hlth Sci & Policy, New York, NY 10029 USA

关键词: Circadian clock;    Adipose tissue;    Inflammation;    Shiftwork;    Insulin resistance;   

DOI  :  10.1016/j.mce.2020.111110

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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