Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein.
Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells.
Valet
P
P
Institut de Physiologie, Institut National de la Santé et de la Recherche Medicale, Université Paul Sabatier, Toulouse, France.
Berlan
M
M
Beauville
M
M
Crampes
F
F
Montastruc
J L
JL
Lafontan
M
M
D000243:Adenosine Deaminase / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D005768:Gastrointestinal Hormones; D009478:Neuropeptide Y; D010455:Peptides; D010566:Virulence Factors, Bordetella; D019894:Peptide YY; D005576:Colforsin; D037342:Pertussis Toxin; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D005990:Glycerol; D004837:Epinephrine