Regulation of leptin release by insulin, glucocorticoids, G(i)-coupled receptor agonists, and pertussis toxin in adipocytes and adipose tissue explants from obese humans in primary culture.
The basal release of leptin by adipocytes from massively obese human subjects incubated for 48 hours in serum-free suspension culture was comparable to that by explants of subcutaneous adipose tissue from the same obese individuals. There was no stimulation due to dexamethasone or insulin alone of leptin release by adipocytes. However, the combination of insulin and dexamethasone doubled leptin release by adipocytes. The release of leptin was also stimulated by agonists of G(i)-coupled receptors (prostaglandin E(2) [PGE(2)], brimonidine [an alpha(2) catecholamine agonist] and cyclopentyladenosine [CPA]) in the presence of dexamethasone. Leptin release by these agents was further enhanced by insulin in both adipocytes and adipose tissue. Pertussis toxin, which irreversibly inactivates G(i) heterotrimers, inhibited leptin release and abolished the stimulatory effects of G(i)-coupled receptor agonists. However, pertussis toxin did not block the stimulation of leptin release by insulin in either adipose tissue or adipocytes. These data indicate that the release of leptin by human adipocytes cultured for 48 hours in a serum-free medium is comparable to that by explants of adipose tissue except that dexamethasone stimulation of leptin release requires the presence of insulin.
Kanu
Alie
A
Department of Molecular Sciences, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38136, USA.
Fain
John N
JN
Bahouth
Suleiman W
SW
Cowan
George S M
GS
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000819:agonists*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D009765:Obesity / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology*; D013268:Stimulation, Chemical
D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D020738:Leptin; D003907:Dexamethasone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go