Scd1 controls de novo beige fat biogenesis through succinate-dependent regulation of mitochondrial complex II

Keli Liu, Liangyu Lin, Qing Li, Yueqing Xue, Fanjun Zheng, Guan Wang, Chunxing Zheng, Liming Du, Mingyuan Hu, Yin Huang, Changshun Shao, Xiangyin Kong, Gerry Melino, Yufang Shi, Ying Wang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Preadipocytes can give rise to either white adipocytes or beige adipocytes. Owing to their distinct abilities in nutrient storage and energy expenditure, strategies that specifically promote “beiging” of adipocytes hold great promise for counterbalancing obesity and metabolic diseases. Yet, factors dictating the differentiation fate of adipocyte progenitors remain to be elucidated. We found that stearoyl-coenzyme A desaturase 1 (Scd1)-deficient mice, which resist metabolic stress, possess augmentation in beige adipocytes under basal conditions. Deletion of Scd1 in mature adipocytes expressing Fabp4 or Ucp1 did not affect thermogenesis in mice. Rather, Scd1 deficiency shifted the differentiation fate of preadipocytes from white adipogenesis to beige adipogenesis. Such effects are dependent on succinate accumulation in adipocyte progenitors, which fuels mitochondrial complex II activity. Suppression of mitochondrial complex II by Atpenin A5 or oxaloacetic acid reverted the differentiation potential of Scd1-deficient preadipocytes to white adipocytes. Furthermore, supplementation of succinate was found to increase beige adipocyte differentiation both in vitro and in vivo. Our data reveal an unappreciated role of Scd1 in determining the cell fate of adipocyte progenitors through succinate-dependent regulation of mitochondrial complex II.

Original languageEnglish (US)
Pages (from-to)2462-2472
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number5
DOIs
StatePublished - Feb 4 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Beige fat biogenesis
  • Mitochondrial complex II
  • Preadipocytes
  • Stearoyl-coenzyme A desaturase 1 (Scd1)
  • Succinate

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