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The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Jan 28; Vol. 23 (3). Date of Electronic Publication: 2022 Jan 28. - Publication Year :
- 2022
-
Abstract
- 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.
- Subjects :
- Adenylate Kinase metabolism
Animals
Blood Glucose
Body Weight
Cell Size
Cells, Cultured
Cysteine Endopeptidases metabolism
Energy Metabolism
Fibroblasts cytology
Fibroblasts drug effects
Fibroblasts metabolism
Insulin adverse effects
Mice
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
Adenosine Triphosphate metabolism
Cysteine Endopeptidases genetics
Gene Deletion
Insulin administration & dosage
Insulin Resistance genetics
Mixed Function Oxygenases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35163456
- Full Text :
- https://doi.org/10.3390/ijms23031536