The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism

International Journal of Molecular Sciences

Amalia Ruiz-Serrano¹  Carsten C. Scholz¹  Svende Pfundstein¹  Roland H. Wenger¹  Agnieszka E. Jucht¹  Andreas M. Bapst¹  Julia Günter¹  Christina N. Boyle²  Thomas A. Lutz²  Josep M. Monné Rodríguez³ 

[1] Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland;Institute of Veterinary Physiology, University of Zurich, 8057 Zurich, Switzerland;Laboratory for Animal Model Pathology (LAMP), Institute of Veterinary Pathology, University of Zurich, 8057 Zurich, Switzerland;

关键词: deubiquitinating enzyme;    energy expenditure;    insulin;    liver;    ubiquitin system;    FIH;   

DOI  :  10.3390/ijms23031536

来源: DOAJ

【 摘 要 】

Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis.

【 授权许可】

Unknown