title: Effects of alpha-lipoic acid on chemerin secretion in 3T3-L1 and human adipocytes.
abstract: Chemerin is a novel adipokine associated with obesity and insulin resistance. α-Lipoic acid (α-LA) has shown beneficial properties on diabetes and obesity. The aim of this study was to examine the effects of α-LA on chemerin production in adipocytes in absence or presence of TNF-α, insulin and AICAR. The potential signaling pathways involved in α-LA effects on chemerin were also analyzed. α-LA actions on chemerin were tested in differentiated 3T3-L1 adipocytes and in some cases in human subcutaneous and omental adipocytes. Chemerin mRNA levels were measured by RT-PCR and the amount of chemerin secreted to culture media was determined by ELISA. α-LA induced a concentration-dependent inhibition on both chemerin secretion and mRNA levels in 3T3-L1 adipocytes. The AMPK activator AICAR and the PI3K inhibitor LY294002 dramatically abrogated both chemerin secretion and gene expression, and further potentiated the inhibitory effect of α-LA on chemerin secretion. Insulin was able to partially reverse the inhibitory action of α-LA on chemerin secretion. α-LA also reduced basal chemerin secretion in both subcutaneous and omental adipocytes from overweight/obese subjects. Moreover, α-LA was able to abolish the stimulatory effects of the pro-inflammatory cytokine TNF-α on chemerin secretion. Our data demonstrated the ability of α-LA to inhibit chemerin production, an adipokine associated to obesity and metabolic syndrome, suggesting that the reduction of chemerin could contribute to the antiobesity/antidiabetic properties described for α-LA.
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Faculty of Health and Physical Activity Science, University SEK, Santiago, Chile.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Prieto-Hontoria
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Department of Nutrition, Diabetes and Metabolism, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Galilea
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Centre for Nutrition Research, University of Navarra, Pamplona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Yoldi
authors.affiliation: Department of Pharmacology and College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinal
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Centre for Nutrition Research, University of Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain; Centre for Nutrition Research, University of Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. Electronic address: mjmoreno@unav.es.
authors.forename: María J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D018925:Chemokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D018925:Chemokines; D007004:Hypoglycemic Agents; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; C478630:RARRES2 protein, human; D012333:RNA, Messenger; C560738:Rarres2 protein, rat; D012265:Ribonucleotides; D014409:Tumor Necrosis Factor-alpha; C523686:chemerin protein, mouse; D000620:Aminoimidazole Carboxamide; D008063:Thioctic Acid; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide
keywords: Adipocytes; Chemerin; Lipoic acid; Obesity