title: Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes.
abstract: Lipoic acid (LA) is a naturally occurring compound with beneficial effects on obesity. The aim of this study was to evaluate its effects on lipolysis in 3T3-L1 adipocytes and the mechanisms involved. Our results revealed that LA induced a dose- and time-dependent lipolytic action, which was reversed by pretreatment with the c-Jun N-terminal kinase inhibitor SP600125, the PKA inhibitor H89, and the AMP-activated protein kinase activator AICAR. In contrast, the PI3K/Akt inhibitor LY294002 and the PDE3B antagonist cilostamide enhanced LA-induced lipolysis. LA treatment for 1 h did not modify total protein content of hormone-sensitive lipase (HSL) but significantly increased the phosphorylation of HSL at Ser(563) and at Ser(660), which was reversed by H89. LA treatment also induced a marked increase in PKA-mediated perilipin phosphorylation. LA did not significantly modify the protein levels of adipose triglyceride lipase or its activator comparative gene identification 58 (CGI-58) and inhibitor G(0)/G(1) switch gene 2 (G0S2). Furthermore, LA caused a significant inhibition of adipose-specific phospholipase A2 (AdPLA) protein and mRNA levels in parallel with a decrease in the amount of prostaglandin E(2) released and an increase in cAMP content. Together, these data suggest that the lipolytic actions of LA are mainly mediated by phosphorylation of HSL through cAMP-mediated activation of protein kinase A probably through the inhibition of AdPLA and prostaglandin E(2).
authors.affiliation: Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Galilea
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Prieto-Hontoria
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martinez
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology; D002787:Sterol Esterase / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology*; D000217:Acyltransferases
chemical_list: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide; D000873:Anthracenes; D002352:Carrier Proteins; D002867:Chromones; D007546:Isoquinolines; D048031:JNK Mitogen-Activated Protein Kinases; D008049:Lipase; D009025:Morpholines; D000070778:Perilipin-1; D010750:Phosphoproteins; D015363:Quinolones; D012265:Ribonucleotides; D002787:Sterol Esterase; D013449:Sulfonamides; D008063:Thioctic Acid; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C021294:cilostamide; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases; C031143:AICA ribonucleotide; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide