期刊
NATURE MEDICINE
卷 21, 期 8, 页码 887-894出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3882
关键词
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资金
- Takeda
- US National Institute of Health [DK028082, DK083694]
- Boston Area Diabetes Endocrinology Research Center (BADERC) [DK057521]
- Instituto de Salud Carlos III [FIS-PI11/00214, FIS-PI12/02631]
- Fondo Europeo de Desarrollo Regional (FEDER), Spain
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R37DK028082, P30DK057521, R01DK083694, R01DK028082] Funding Source: NIH RePORTER
Nicotinamide N-methyltransferase (Nnmt) methylates nicotinamide, a form of vitamin 83, to produce N-1-methylnicotinamide (MNAM). Nnmt has emerged as a metabolic regulator in adipocytes, but its role in the liver, the tissue with the strongest Nnmt expression, is not known. In spite of its overall high expression, here we find that hepatic expression of Nnmt is highly variable and correlates with multiple metabolic parameters in mice and humans. Further, we find that suppression of hepatic Nnmt expression in vivo alters glucose and cholesterol metabolism and that the metabolic effects of Nnmt in the liver are mediated by its product MNAM. Supplementation of high-fat diet with MNAM decreases serum and liver cholesterol and liver triglycerides levels in mice. Mechanistically, increasing Nnmt expression or MNAM levels stabilizes sirtuin 1 protein, an effect that is required for their metabolic benefits. In summary, we describe here a novel regulatory pathway for vitamin B3 that could provide a new opportunity for metabolic disease therapy.
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