Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A.
A G-protein coupled receptor to niacin (nicotinic acid) was identified recently but the physiological/pharmacological role of the receptor remains poorly defined. We present our studies to demonstrate that HM74A, but not HM74, binds niacin at high affinities and effectively mediates Gi signaling events in human embryonic kidney HEK293 cells as well as in 3T3L1 adipocytes expressing HM74A. Furthermore, HM74A, but not HM74, expressed in differentiated 3T3L1 adipocytes effectively mediated inhibition of lipolysis by niacin. Our results provided direct evidence indicating that HM74A, but not HM74, was sufficient to mediate anti-lipolytic effect of niacin in adipose tissue.
Zhang
Youyan
Y
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Schmidt
Robert J
RJ
Foxworthy
Patricia
P
Emkey
Renee
R
Oler
Jennifer K
JK
Large
Thomas H
TH
Wang
He
H
Su
Eric W
EW
Mosior
Marion K
MK
Eacho
Patrick I
PI
Cao
Guoqing
G
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006801:Humans; D007668:Kidney; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009525:Niacin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*
C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin