2. Academic Validation
  3. PPA1 promotes adipogenesis by regulating the stability of C/EBPs

PPA1 promotes adipogenesis by regulating the stability of C/EBPs

  • Cell Death Differ. 2024 May 18. doi: 10.1038/s41418-024-01309-2.
Yangyang Wu # 1 2,  Yue Sun # 3,  Yuqing Song 1,  Jiateng Wang 1,  Ye Han 1,  Nan Yang 1,  Haiyan Lin 4,  Ye Yin 5,  Xiao Han 6
Affiliations

Affiliations

  • 1 Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • 2 Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing Medical University, Nanjing, China.
  • 3 Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • 4 Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China. linda@njmu.edu.cn.
  • 5 Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China. yin@njmu.edu.cn.
  • 6 Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China. hanxiao@njmu.edu.cn.
  • # Contributed equally.
PMID: 38762596 DOI: 10.1038/s41418-024-01309-2
Abstract

Adipogenesis significantly contributes to healthy adipose tissue expansion in obesity. Increasing adipocyte number or function to alleviate adipose tissue overload could serve as a therapeutic strategy for both lipodystrophy and obesity-related metabolic syndrome. Inorganic pyrophosphatase (PPA1) is an Enzyme that catalyzes the hydrolysis of pyrophosphate (PPi) and is involved in many biochemical reactions, but its function in adipose tissue has not been studied previously. In this study, we demonstrated that adipose-specific PPA1 knockout (PPA1AKO) mice showed lipodystrophy and spontaneously developed hepatic steatosis and severe Insulin resistance under normal chow diet feeding. PPA1 deficiency suppressed the differentiation of primary adipocyte precursors and 3T3-L1 cells. Notably, PPA1 overexpression can restore inhibited adipogenesis in preadipocytes isolated from db/db mice and type 2 diabetes patients. Mechanistic studies have revealed that PPA1 acts as a positive regulator of early adipocyte differentiation by promoting CCAAT/enhancer-binding proteinβ and δ (C/EBPβ and δ) protein stability. Moreover, the function of PPA1 in adipogenesis is independent of its PPi catalytic activity. Collectively, our in vivo and in vitro findings demonstrated that PPA1 is a novel critical upstream regulator of adipogenesis, controlling adipose tissue development and whole-body metabolic homeostasis.

Figures
Products