title: Beta-3 agonist-induced lipolysis and nitric oxide production: relationship to PPARgamma agonist/antagonist and AMP kinase modulation.
abstract: PPARgamma receptor agonist -troglitazone increases insulin sensitivity in visceral adipocytes and also increases fat mass. Beta-3 adrenergic receptor agonists mediate lipolysis and NO production (iNOS transcription) in visceral adipocytes. Troglitazone could possibly interfere with Beta-3-triggered lipolysis. We tested the crosstalk between PPARgamma agonist and Beta-3 agonist pathways on lipolysis and NO production in first 24 hours of treatment. Isolated epididymal rat adipocytes were cultivated in DMEM for 24 hours with treatment with Beta-3 agonist - BRL-37344, PPARgamma agonist - troglitazone, PPARgamma antagonist - SR-202 and AMPK blocker - compound C alone as well as in combinations. After 24 hours, lipolysis was measured by free glycerol, NO production by Griess reagent and iNOS mRNA by qRT-PCR. BRL-37344 increased lipolysis and NO production with iNOS transcription. Troglitazone increased all the three parameters as well but less than BRL-37344. Combination of troglitazone or SR-202 with BRL-37344 decreased NO production, iNOS transcription and lipolysis triggered before adding of BRL-37344. Compound C completely blocked the effect of troglitazone (and SR-202 as well) on BRL-37344. PPARgamma agonist/antagonist interferes with Beta-3 agonist activity in 24 hours. Troglitazone/SR-202 effect on Beta-3 triggered lipolysis and iNOS mRNA production is probably not PPAR gamma- but rather AMPK-dependent in first 24 hours (AMPK blocker - compound C blocked the effect).
authors: Institute of Pharmacology, First Faculty of Medicine, Charles University, Albertov 4, 120 00 Prague 2, Czech Republic. hodis@atlas.cz
authors: Jiří
authors: J
authors: Hodis
authors: Radka
authors: R
authors: Vaclavíková
authors: Hassan
authors: H
authors: Farghali
mesh_terms: D000263:Adenylate Kinase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D002839:Chromans; D004983:Ethanolamines; D009943:Organophosphorus Compounds; D047495:PPAR gamma; D045162:Thiazolidinediones; D009569:Nitric Oxide; C057368:BRL 37344; D019001:Nitric Oxide Synthase; D000263:Adenylate Kinase; D000077288:Troglitazone; D005990:Glycerol; C051602:mifobate