Ube2i deletion in adipocytes causes lipoatrophy in mice

Molecular Metabolism

Stephanie A. Pangas¹  Natasha Chernis²  Robert Sharp²  Peter M. Masschelin²  Zheng Sun²  Xin Li³  David D. Moore⁴  Pradip K. Saha⁴  Jessica B. Felix⁵  Kang Ho Kim⁵  Aaron R. Cox⁵  Sean M. Hartig⁵  Shawn M. Briley⁵ 

[1] Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA;Department of Medicine, Baylor College of Medicine, Houston, TX, USA;Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA;Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA;Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, Houston, TX, USA;

关键词: Ube2i;    Lipodystrophy;    Adipose tissue;    Lipid metabolism;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objective: White adipose tissue (WAT) expansion regulates energy balance and overall metabolic homeostasis. The absence or loss of WAT occurring through lipodystrophy and lipoatrophy contributes to the development of hepatic steatosis and insulin resistance. We previously demonstrated that sole small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ube2i represses human adipocyte differentiation. The role of Ube2i during WAT development remains unknown. Methods: To determine how Ube2i impacts body composition and energy balance, we generated adipocyte-specific Ube2i knockout mice (Ube2ia-KO). CRISPR/Cas9 gene editing inserted loxP sites flanking exons 3 and 4 at the Ube2i locus. Subsequent genetic crosses to Adipoq-Cre transgenic mice allowed deletion of Ube2i in white and brown adipocytes. We measured multiple metabolic endpoints that describe energy balance and carbohydrate metabolism in Ube2ia-KO and littermate controls during postnatal growth. Results: Surprisingly, Ube2ia-KO mice developed hyperinsulinemia and hepatic steatosis. Global energy balance defects emerged from dysfunctional WAT marked by pronounced local inflammation, loss of serum adipokines, hepatomegaly, and near absence of major adipose tissue depots. We observed progressive lipoatrophy that commences in the early adolescent period. Conclusions: Our results demonstrate that Ube2i expression in mature adipocytes allows WAT expansion during postnatal growth. Deletion of Ube2i in fat cells compromises and diminishes adipocyte function that induces WAT inflammation and ectopic lipid accumulation in the liver. Our findings reveal an indispensable role for Ube2i during white adipocyte expansion and endocrine control of energy balance.

【 授权许可】

Unknown