Obesity-induced PARIS (ZNF746) accumulation in adipose progenitor cells leads to attenuated mitochondrial biogenesis and impaired adipogenesis

Author:

Hachiya Kazuki1,Deguchi Yusuke1,Hirata Takuro1,Arikawa Tomoya1,Fukai Hiroto1,Esashi Tatsuhiro1,Nagasawa Kota1,Mizunoe Yuhei1,Nozaki Yuka1,Kobayashi Masaki2,Higami Yoshikazu1

Affiliation:

1. 1. Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science

2. 2. Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu Universit

Abstract

Abstract White adipose tissue (WAT) is critical for whole-body energy metabolism, and its dysfunction leads to various metabolic disorders. In recent years, many studies have suggested that impaired mitochondria may contribute to the obesity-related decline in adipose tissue function, but the detailed mechanisms remain unclear. To investigate these mechanisms, we carried out a comprehensive analysis of WAT from mice with diet-induced obesity. The transcription factor Parkin interactive substrate (PARIS or ZNF746), which suppresses the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key regulator of mitochondrial biogenesis, was found to be accumulated in adipose progenitor cells from obese mice. Furthermore, we demonstrated that 3T3-L1 preadipocytes with overexpression of PARIS protein exhibited decreased mitochondrial biogenesis and impaired adipogenesis. Our results suggest that the accumulation of PARIS protein may be a novel component of the pathogenesis of obesity-related dysfunction in WAT.

Publisher

Research Square Platform LLC

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