Naa10p Inhibits Beige Adipocyte-Mediated Thermogenesis through N-α-acetylation of Pgc1α
| Autor: | Chen-Cheng Lee, Yi-Chun Shih, Yi-Cheng Chang, Ramanan Devaraj, Ming-Lun Kang, Li-Jung Juan, Lee-Ming Chuang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Adolescent White adipose tissue Biology Diet High-Fat Mice Young Adult 03 medical and health sciences 0302 clinical medicine Gene expression Animals Humans Adipocytes Beige N-Terminal Acetyltransferase E Obesity Molecular Biology N-Terminal Acetyltransferase A Adiposity Aged 030304 developmental biology Mice Knockout chemistry.chemical_classification 0303 health sciences Acetylation Thermogenesis Lipid metabolism Cell Biology Adipose Tissue Beige Middle Aged Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Cell biology Mice Inbred C57BL N-terminus Disease Models Animal HEK293 Cells Phenotype Enzyme chemistry Case-Control Studies NIH 3T3 Cells Female Energy Metabolism Protein Processing Post-Translational 030217 neurology & neurosurgery Function (biology) Signal Transduction |
| Zdroj: | Molecular Cell. 76:500-515.e8 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2019.07.026 |
| Popis: | Diet-induced obesity can be caused by impaired thermogenesis of beige adipocytes, the brown-like adipocytes in white adipose tissue (WAT). Promoting brown-like features in WAT has been an attractive therapeutic approach for obesity. However, the mechanism underlying beige adipocyte formation is largely unknown. N-α-acetyltransferase 10 protein (Naa10p) catalyzes N-α-acetylation of nascent proteins, and overexpression of human Naa10p is linked to cancer development. Here, we report that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, and beige adipocyte differentiation. Mechanistically, Naa10p acetylates the N terminus of Pgc1α, which prevents Pgc1α from interacting with Pparγ to activate key genes, such as Ucp1, involved in beige adipocyte function. Consistently, fat tissues of obese human individuals show higher NAA10 expression. Thus, Naa10p-mediated N-terminal acetylation of Pgc1α downregulates thermogenic gene expression, making inhibition of Naa10p enzymatic activity a potential strategy for treating obesity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|