Naa10p Inhibits Beige Adipocyte-Mediated Thermogenesis through N-α-acetylation of Pgc1α
Journal
Molecular Cell
Journal Volume
76
Journal Issue
3
Pages
500-515
Date Issued
2019
Author(s)
Lee, Chen-Cheng
Shih, Yi-Chun
Kang, Ming-Lun
Devaraj, Ramanan
Juan, Li-Jung
Abstract
Lee et al. reveal that Naa10p-mediated N-terminal acetylation of Pgc1α inhibits beige thermogenesis and promotes diet-induced obesity (DIO) in mice. Together with the fact that NAA10 expression positively correlates with human obesity, their results suggest that inhibiting the enzymatic activity of Naa10p in adipose tissues may suppress DIO. ? 2019 Elsevier Inc.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. ? 2019 Elsevier Inc.
Subjects
messenger RNA; peptide alpha n acetyltransferase; peptide alpha n acetyltransferase 10; peroxisome proliferator activated receptor gamma coactivator 1alpha; unclassified drug; uncoupling protein 1; NAA10 protein, human; Naa10 protein, mouse; peptide alpha n acetyltransferase A; peptide alpha n acetyltransferase E; peroxisome proliferator activated receptor gamma coactivator 1alpha; PPARGC1A protein, human; Ppargc1a protein, mouse; adipogenesis; adipose tissue; adult; aged; amino terminal sequence; animal cell; animal experiment; animal model; animal tissue; Article; beige adipocyte; cell differentiation; controlled study; diet-induced obesity; down regulation; energy expenditure; enzyme activity; gene deletion; gene knockout; gene overexpression; glucose tolerance test; human; human tissue; in vitro study; insulin tolerance test; major clinical study; male; mitochondrial respiration; mouse; mRNA expression level; nonhuman; protein acetylation; protein protein interaction; thermogenesis; acetylation; adolescent; animal; beige adipocyte; beige adipose tissue; C57BL mouse; case control study; disease model; energy metabolism; enzymology; female; genetics; HEK293 cell line; knockout mouse; lipid diet; metabolism; middle aged; NIH 3T3 cell line; obesity; pathophysiology; phenotype; protein processing; signal transduction; young adult; Acetylation; Adipocytes, Beige; Adipose Tissue, Beige; Adiposity; Adolescent; Adult; Aged; Animals; Case-Control Studies; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Female; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; N-Terminal Acetyltransferase A; N-Terminal Acetyltransferase E; NIH 3T3 Cells; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phenotype; Protein Processing, Post-Translational; Signal Transduction; Thermogenesis; Young Adult [SDGs]SDG3
SDGs
Type
journal article