title: Lipoic acid inhibits adiponectin production in 3T3-L1 adipocytes.
abstract: Lipoic acid (LA) is a naturally occurring compound with antioxidant properties. Recent attention has been focused on the potential beneficial effects of LA on obesity and related metabolic disorders. Dietary supplementation with LA prevents insulin resistance and upregulates adiponectin, an insulin-sensitizing adipokine, in obese rodents. The aim of this study was to investigate the direct effects of LA on adiponectin production in cultured adipocytes, as well as the potential signaling pathways involved. For this purpose, fully differentiated 3T3-L1 adipocytes were treated with LA (1-500 μM) during 24 h. The amount of adiponectin secreted to media was detected by ELISA, while adiponectin mRNA expression was determined by RT-PCR. Treatment with LA induced a dose-dependent inhibition on adiponectin gene expression and protein secretion. Pretreatment with the PI3K inhibitor LY294002 inhibited adiponectin secretion and mRNA levels, and significantly potentiated the inhibitory effect of LA on adiponectin secretion. The AMPK activator AICAR also reduced adiponectin production, but surprisingly, it was able to reverse the LA-induced inhibition of adiponectin. The JNK inhibitor SP600125 and the MAPK inhibitor PD98059 did not modify the inhibitory effect of LA on adiponectin. In conclusion, our results revealed that LA reduces adiponectin secretion in 3T3-L1 adipocytes, which contrasts with the stimulation of adiponectin described after in vivo supplementation with LA, suggesting that an indirect mechanism or some in vivo metabolic processing is involved.
authors: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
authors: Pedro L
authors: PL
authors: Prieto-Hontoria
authors: Marta
authors: M
authors: Fernández-Galilea
authors: Patricia
authors: P
authors: Pérez-Matute
authors: J Alfredo
authors: JA
authors: Martínez
authors: María J
authors: MJ
authors: Moreno-Aliaga
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors; D005419:Flavonoids / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D000873:Anthracenes; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; D012333:RNA, Messenger; D012265:Ribonucleotides; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000620:Aminoimidazole Carboxamide; D008063:Thioctic Acid; D019869:Phosphatidylinositol 3-Kinases; D055372:AMP-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C031143:AICA ribonucleotide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one