BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis

Shu Wen Qian, Yan Tang, Xi Li, Yuan Liu, You You Zhang, Hai Yan Huang, Rui Dan Xue, Hao Yong Yu, Liang Guo, Hui Di Gao, Yan Liu, Xia Sun, Yi Ming Li, Wei Ping Jia, Qi Qun Tang

Research output: Contribution to journalArticle

Abstract

Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator- activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number9
DOIs
StatePublished - Feb 26 2013
Externally publishedYes

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Keywords

  • Adipocyte terminal differentiation
  • Brown adipose tissue
  • Metabolism
  • Mitochondria

ASJC Scopus subject areas

  • General

Cite this

Qian, S. W., Tang, Y., Li, X., Liu, Y., Zhang, Y. Y., Huang, H. Y., Xue, R. D., Yu, H. Y., Guo, L., Gao, H. D., Liu, Y., Sun, X., Li, Y. M., Jia, W. P., & Tang, Q. Q. (2013). BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis. Proceedings of the National Academy of Sciences of the United States of America, 110(9). https://doi.org/10.1073/pnas.1215236110