title: Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes.
abstract: METHODS
  Lipoic acid (LA) is an antioxidant with therapeutic potential on several diseases such as diabetes and obesity. Hyperleptinemia and oxidative stress play a major role in the development of obesity-linked diseases. The aim of this study was to examine in vivo and in vitro the effects of LA on leptin production, as well as to elucidate the mechanisms and signalling pathways involved in LA actions.
  
  
  RESULTS
  Dietary supplementation with LA decreased both circulating leptin, and adipose tissue leptin mRNA in rats. Treatment of 3T3-L1 adipocytes with LA caused a concentration-dependent inhibition of leptin secretion and gene expression. Moreover, LA stimulated the anaerobic utilization of glucose to lactate, which negatively correlated with leptin secretion. Furthermore, LA enhanced phosphorylation of Sp1 and inhibited Sp1 transcriptional activity in 3T3-L1 adipocytes. Moreover, LA inhibited Akt phosphorylation, a downstream target of phosphatidylinositol 3-kinase (PI3K). Treatment with the PI3K inhibitor LY294002 mimicked LA actions, dramatically inhibiting both leptin secretion and gene expression and stimulating Sp1 phosphorylation.
  
  
  CONCLUSIONS
  All of these data suggest that the phosphorylation of Sp1 and the accompanying reduced DNA-binding activity are likely to be involved in the inhibition of leptin induced by LA, which could be mediated in part by the abrogation of the PI3K/Akt pathway.
authors.affiliation: Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Prieto-Hontoria
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Galilea
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.forename: María J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D002867:Chromones; D004041:Dietary Fats; D020738:Leptin; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D016329:Sp1 Transcription Factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008063:Thioctic Acid; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4; D005947:Glucose