Adipose tissue as a source of nicotinamide N-methyltransferase and homocysteine.
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.
Riederer
Monika
M
Institute of Molecular Biosciences, University of Graz, Heinrichstrasse 31A, A-8010 Graz, Austria. monika.riederer@uni-graz.at
Erwa
Wolfgang
W
Zimmermann
Robert
R
Frank
Sasa
S
Zechner
Rudolf
R
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology*; D050156:Adipogenesis; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009525:Niacin / Q000494:pharmacology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D050903:Nicotinamide N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D006710:Homocysteine; D009536:Niacinamide; D009525:Niacin; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase; C494407:Nnmt protein, mouse; C024058:N(1)-methylnicotinamide