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
| Autor: | Daisuke Yamada, Yu-Lai Wang, Shinji Miura, Keiji Wada, Rieko Setsuie, Yasuyuki Suzuki, Hiromi Fujita, Mari Suzuki, Osamu Ezaki, Nobutsune Ichihara, Tomohiro Kabuta |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Adipose Tissue White Adipose tissue Ubiquitin C-Terminal Hydrolase AMP-Activated Protein Kinases Biochemistry Gene Expression Regulation Enzymologic Mice Ubiquitin AMP-activated protein kinase Internal medicine Genetics medicine Animals Obesity Muscle Skeletal Protein kinase A Molecular Biology Cells Cultured biology Body Weight Skeletal muscle AMPK Fibroblasts Animal Feed Diet Glucose Endocrinology medicine.anatomical_structure Body Composition biology.protein Female Energy Metabolism Ubiquitin Thiolesterase cGMP-dependent protein kinase Biotechnology |
| Zdroj: | The FASEB Journal. 23:4148-4157 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | 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 ubiquitin C-terminal hydrolase (UCH)-L3, one of the deubiquitinating enzymes, contributes to the regulation of 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 beta-oxidation, leading to the elevation of the whole-body energy expenditure. Consistently, increased activation of AMPK and fatty acid beta-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. |
| Databáze: | OpenAIRE |
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