Direct effect of ghrelin on leptin production by cultured rat white adipocytes.
OBJECTIVE
Because ghrelin is known to stimulate adipogenesis, we tested whether ghrelin could contribute to the maintenance of homeostasis, directly affecting rat white adipocyte leptin production.


METHODS
Isolated retroperitoneal adipocytes were cultured for 0.5 to 48 hours without (baseline) or with (0.001 to 1 nM) ghrelin alone or in combination with insulin (0.01 to 10 nM) or dexamethasone (1 to 100 nM). Adipocytes were also incubated with ghrelin and inhibitors either of RNA (actinomycin D) or protein synthesis (cycloheximide) or with several concentrations (10 to 1000 nM) of a specific ghrelin antagonist. When cultures were terminated, we evaluated adipocyte leptin secretion and ob mRNA expression.


RESULTS
Our data indicate that ghrelin directly enhanced adipocyte leptin release and ob mRNA expression, that the leptin-releasing activity of ghrelin was additive to the action of both insulin and dexamethasone and was abrogated by protein synthesis inhibitors, and that effects of ghrelin on adipocyte ob mRNA expression and release were blocked by coincubation with the specific growth hormone secretagogue receptor 1a antagonist.


CONCLUSIONS
Our study supports the ability of ghrelin to enhance white adipose tissue leptin production by a direct receptor-mediated effect. This activity of ghrelin could play a potentially significant role in rapid restoration of homeostasis after food intake.
Giovambattista
Andrés
A
Neuroendocrine Unit, IMBICE (CONICET-CICPBA), P.O. Box 403, 1900 La Plata, Argentina.
Piermaría
Judith
J
Suescun
María O
MO
Calandra
Ricardo S
RS
Gaillard
Rolf C
RC
Spinedi
Eduardo
E
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D054439:Ghrelin; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000096:biosynthesis*; D008297:Male; D036361:Peptide Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D036361:Peptide Hormones; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide