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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Ssu72 phosphatase orchestrates obesogenic adipogenesis and metabolic homeostasis during nutrient excess
Si Chen1, Joon-Sup Yoon1, Eun-Ji Park1
1Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea.
Abstract:
White adipose tissue (WAT) dysfunction under nutrient excess is a central driver of obesity and its related metabolic disorders. Maintaining precise regulation of adipogenesis and lipid metabolism in WAT is essential for systemic energy balance and metabolic health. Here, we identify Ssu72 phosphatase as a critical regulator of adipogenesis required for WAT expansion. Ssu72 expression is elevated in obese WAT. Notably, adipocyte-specific deletion of Ssu72 in mice confers resistance to high-fat diet (HFD)-induced obesity, accompanied by improved insulin sensitivity and altered energy expenditure. Ssu72 deficiency diminishes HFD-induced adipocyte hypertrophy and inflammation in WAT. Mechanistically, loss of Ssu72 inhibits PPARγ-mediated adipogenesis and lipid storage by hyperphosphorylation of GSK3β, resulting in suppression of WAT expansion. In addition, metabolic alterations in Ssu72-deleted WAT are reversed by restoring Ssu72 expression. Taken together, our findings reveal a novel adipocyte Ssu72-GSK3β axis that regulates obesogenic adipogenesis in white adipocytes, suggesting that Ssu72 is a promising target for controlling diet-induced obesity and whole-body metabolic homeostasis.
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