Effects of pain controlling neuropeptides on human fat cell lipolysis.
OBJECTIVE
Neuropeptides NPFF and NPSF are involved in pain control, acting through the G-protein coupled receptors (GPR)74 (high affinity for NPFF) and GPR147 (equal affinity for NPFF and NPSF). GPR74 also inhibits catecholamine-induced adipocyte lipolysis and regulates fat mass in humans. The aim of this study was to compare the effects of NPFF and NPSF on noradrenaline-induced lipolysis and to determine the expression of their receptors in human fat cells.


METHODS
Adipose tissue was obtained during surgery. Adipocytes were prepared and kept in primary culture. Lipolysis, protein expression and gene expression were determined.


RESULTS
NPFF counteracted noradrenaline-induced lipolysis, which was more marked after 48 h than after 4 h exposure and was solely attributed to inhibition of beta-adrenoceptor signalling. NPSF counteracted noradrenaline-induced lipolysis maximally after 4 h of exposure, which was attributed to a combination of inhibition of beta-adrenoceptor signalling and decreased activation of the protein kinase-A hormone sensitive lipase complex by cyclic AMP. Both neuropeptides were effective in nanomolar concentrations. NPFF and NPSF had no effects on the expression of genes involved in catecholamine signal transduction. Both GPR74 and GPR147 were expressed at the protein level in fat cells from various adipose regions. GPR74 mRNA levels were higher in adipose tissue from obese as compared with non-obese subjects. High gene expression of either receptor correlated with low noradrenaline-induced lipolysis (P<0.05).


CONCLUSIONS
Pain controlling neuropeptides NPFF and NPSF may be important for the regulation of lipolysis in man probably acting through GPR74 and GPR147. At low concentrations they inhibit catecholamine-induced lipolysis through rapid and long-term post-transcriptional effects at several steps in adrenoceptor signalling in fat cells.
van Harmelen
V
V
Department of Medicine, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden.
Dicker
A
A
Sjölin
E
E
Blomqvist
L
L
Wirén
M
M
Hoffstedt
J
J
Rydén
M
M
Arner
P
P
D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D005260:Female; D006801:Humans; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D018013:Receptors, Neuropeptide / Q000502:physiology; D055815:Young Adult
D009479:Neuropeptides; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; C414382:neuropeptide SF; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide