Inhibition of leptin release by atrial natriuretic peptide (ANP) in human adipocytes.
The addition of atrial natriuretic peptide (ANP) to isolated human adipocytes in primary culture from very obese individuals resulted in an inhibition of leptin release after a 24- or 48-hr incubation. There was also an inhibition of leptin release by isoproterenol (ISO) that was partially reversed by insulin, whereas the inhibition due to ANP was unaffected. Similar results were seen with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide (H-89), which is a cell-permeable inhibitor of protein kinase A. H-89 markedly reduced the effects of ISO on both lipolysis and leptin release without affecting the stimulation of lipolysis or the inhibition of leptin release due to ANP. Inhibition of endogenous nitric oxide formation using N(omega)-nitro-L-arginine resulted in a 20% increase in leptin release over 48 hr, which suggests that the nitric oxide/cyclic GMP pathway might play a small role in the regulation of endogenous leptin release. Similarly, the addition of the nitric oxide donor (Z)-1-[2-aminoethyl)-N-(2-aminoethyl)diazen-1-ium-1,2-diolate (DETA NONOate) at 0.1 or 1 microM to explants of human adipose tissue enhanced lipolysis by 29%. Our data demonstrate that the lipolytic effect of ANP is probably secondary to stimulation of cyclic GMP accumulation in human adipocytes, and this is accompanied by an inhibition of leptin release.
Fain
John N
JN
Department of Molecular Sciences, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. jfain@utmem.edu
Kanu
Alie
A
Bahouth
Suleiman W
SW
Cowan
George S M
GS
Lloyd Hiler
M
M
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects*; D009569:Nitric Oxide; D037342:Pertussis Toxin / Q000494:pharmacology
D007328:Insulin; D020738:Leptin; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D037342:Pertussis Toxin; D006152:Cyclic GMP