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细胞和生理昼夜节律机制驱动了细胞的昼夜增殖和白色脂肪组织的扩张。

Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue.

机构信息

Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center, Houston, TX, 77030, USA.

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, 04103, Leipzig, Germany.

出版信息

Nat Commun. 2021 Jun 9;12(1):3482. doi: 10.1038/s41467-021-23770-0.

Abstract

Hyperplastic expansion of white adipose tissue (WAT) relies in part on the proliferation of adipocyte precursor cells residing in the stromal vascular cell fraction (SVF) of WAT. This study reveals a circadian clock- and feeding-induced diurnal pattern of cell proliferation in the SVF of visceral and subcutaneous WAT in vivo, with higher proliferation of visceral adipocyte progenitor cells subsequent to feeding in lean mice. Fasting or loss of rhythmic feeding eliminates this diurnal proliferation, while high fat feeding or genetic disruption of the molecular circadian clock modifies the temporal expression of proliferation genes and impinges on diurnal SVF proliferation in eWAT. Surprisingly, high fat diet reversal, sufficient to reverse elevated SVF proliferation in eWAT, was insufficient in restoring diurnal patterns of SVF proliferation, suggesting that high fat diet induces a sustained disruption of the adipose circadian clock. In conclusion, the circadian clock and feeding simultaneously impart dynamic, regulatory control of adipocyte progenitor proliferation, which may be a critical determinant of adipose tissue expansion and health over time.

摘要

白色脂肪组织 (WAT) 的过度增生部分依赖于位于 WAT 基质血管细胞部分 (SVF) 的脂肪细胞前体细胞的增殖。本研究揭示了体内内脏和皮下 WAT 的 SVF 中存在生物钟和进食诱导的细胞增殖的昼夜节律模式,在 lean mice 中,进食后内脏脂肪祖细胞的增殖更高。禁食或节律性进食的丧失消除了这种昼夜增殖,而高脂肪喂养或分子生物钟的遗传破坏改变了增殖基因的时间表达,并影响 eWAT 中 SVF 的昼夜增殖。令人惊讶的是,足以逆转 eWAT 中 SVF 增殖升高的高脂肪饮食逆转,不足以恢复 SVF 增殖的昼夜模式,表明高脂肪饮食诱导脂肪生物钟的持续破坏。总之,生物钟和进食同时对脂肪祖细胞增殖施加动态的调节控制,这可能是脂肪组织扩张和随时间健康的关键决定因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3b4/8190103/bcea79721a1d/41467_2021_23770_Fig1_HTML.jpg

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