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Effects of alpha-lipoic acid on chemerin secretion in 3T3-L1 and human adipocytes
Affiliation:1. Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain;2. Faculty of Health and Physical Activity Science, University SEK, Santiago, Chile;3. HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain;4. Department of Nutrition, Diabetes and Metabolism, Pontificia Universidad Católica de Chile, Santiago, Chile;5. Centre for Nutrition Research, University of Navarra, Pamplona, Spain;6. Department of Pharmacology and College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada;7. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Pamplona, Spain;8. Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain;1. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan;2. Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan;3. Department of Medicine, Taipei Medical University, Taipei;4. Department of Sport Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;5. Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei, Taiwan;6. Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;7. Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan
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.
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