期刊
ATHEROSCLEROSIS
卷 204, 期 2, 页码 412-417出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2008.09.015
关键词
NNMT; Nicotinamide; Methyltransferase; Adipose tissue; Homocysteine; Nicotinic acid; Atherosclerosis
资金
- Austrian Science Fund (FWF)
- Project SFB Lipotox [F3001, F3002]
- Austrian Federal Ministry of Science and Research
- GENAU
- Genomics of Lipid-assciated Disorder (GOLD)
- [P-19473-1305]
- Austrian Science Fund (FWF) [Z 136, F 3002] Funding Source: researchfish
Nicotinamide N-methyltransferase (NNMT) catalyses the conversion of nicotinamide to 1-methylnicotinamide and plays an important role in hepatic detoxification reactions. Here we show that, in addition to the liver, 3T3-L1 adipocytes as well as human and murine adipose tissue explants express high amounts of enzymatically active NNMT. NNMT mRNA levels and enzyme activity increased in 3T3-L1 cells in a differentiation-dependent manner. Homocysteine, the atherogenic product of the NNMT-catalyzed reaction, was secreted from 3T3-L1 cells or adipose tissue cultures. Homocysteine release increased during 3T3-L1 differentiation and was reduced when adipose tissue was treated with the NNMT inhibitor 1-methylnicotinamide. Nicotinic acid (NA), a widely used drug to lower elevated plasma lipid levels, induced NNMT enzyme activity in white adipose tissue of mice. In tissue culture nicotinamide treatment led to an increase in adipose tissue homocysteine secretion. These data support the concept that adipose tissue NNMT contributes to the increased plasma homocysteine levels in patients treated with NA. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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