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

Aleix Ribas-Latre, Rafael Bravo Santos, Baharan Fekry, Yomna M. Tamim, Samay Shivshankar, Alaa M. T. Mohamed, Corrine Baumgartner, Christopher Kwok, Claudia Gebhardt, Angielyn Rivera, Zhanguo Gao, Kai Sun, John T. Heiker, Brad E. Snyder, Mikhail G. Kolonin and Kristin L. Eckel-Mahan ()
Additional contact information
Aleix Ribas-Latre: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Rafael Bravo Santos: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Baharan Fekry: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Yomna M. Tamim: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Samay Shivshankar: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Alaa M. T. Mohamed: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Corrine Baumgartner: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Christopher Kwok: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Claudia Gebhardt: Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig
Angielyn Rivera: Memorial Hermann Texas Medical Center
Zhanguo Gao: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Kai Sun: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
John T. Heiker: Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig
Brad E. Snyder: Memorial Hermann Texas Medical Center
Mikhail G. Kolonin: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center
Kristin L. Eckel-Mahan: Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23770-0

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