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- Title
Ubiquitin C-terminal hydrolase-L3-knockout mice are resistant to diet-induced obesity and show increased activation of AMP-activated protein kinase in skeletal muscle.
- Authors
Setsuie, Rieko; Suzuki, Mari; Kabuta, Tomohiro; Fujita, Hiromi; Miura, Shinji; Ichihara, Nobutsune; Yamada, Daisuke; Yu-Lai Wang; Ezaki, Osamu; Suzuki, Yasuyuki; Wada, Keiji
- Abstract
Obesity results from the dysregulation of energy balance throughout the entire body. Although the ubiquitin system participates in many cellular processes, its contribution to the balance of energy in the body remains poorly understood. Here, we show that ubiqultin C-terminal hydrolase (UCH)-L3, one of the deubiqullinating enzymes, contributes to the regulation metabolism. Uchl3-/- mice displayed a reduction of adipose tissue mass and were protected against high-fat diet (HFD)-induced obesity and insulin resistance. Uchl3-/- mice given both a normal chow and an HFD had an increased whole-body energy expenditure accounting for the reduction of adipose tissue mass Activation of AMP-activated protein kinase (AMPK) in skeletal muscle has been reported to increase fatty acid t-oxidation, leading to the elevation of the whole-body energy expenditure. Consistently, increased activation of AMPK and fatty acid β-oxidation was observed in skeletal muscle of Uchl3-/- mice. Mouse embryonic fibroblasts derived from Uchl3-/- mice also showed increased activation of AMPK, indicating that UCH-L3 is involved in a cell-autonomous down-regulation of AMPK. These results suggest a role for UCH-L3 in the regulation of AMPK activity and whole-body energy metabolism.
- Subjects
OBESITY; UBIQUITIN; BIOENERGETICS; ENZYMES; INSULIN resistance; PROTEIN kinases
- Publication
FASEB Journal, 2009, Vol 23, Issue 12, p4148
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.09-132217