Lipoic acid inhibits adiponectin production in 3T3-L1 adipocytes
- 498 Downloads
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.
KeywordsLipoic acid Obesity Adiponectin Adipocytes
This work has been supported by the Ministry of Science and Innovation of the Government of Spain (AGL 2009-10873/ALI and AGL 2006-04716/ALI) and by Línea Especial: “Nutrición, Obesidad y Salud” (University of Navarra). PL Prieto-Hontoria was supported by a research grant by Danone Institute, Spain. CTP, CIBERobn, and RETICS Network are gratefully acknowledged.
Conflict of interest
The authors declare no conflict of interest.
- 8.Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377(9765):557–567PubMedCrossRefGoogle Scholar
- 12.Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS, Yun JY, Namgoong IS, Ha J, Park IS, Lee IK, Viollet B, Youn JH, Lee HK, Lee KU (2004) Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic amp-activated protein kinase. Nat Med 10(7):727–733PubMedCrossRefGoogle Scholar
- 22.Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Martinez JA, Moreno-Aliaga MJ (2013) Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats. Eur J Nutr (in press)Google Scholar
- 32.Wang YM, Lin XF, Shi CM, Lu L, Qin ZY, Zhu GZ, Cao XG, Ji CB, Qiu J, Guo XR (2012) Alpha-lipoic acid protects 3T3-L1 adipocytes from NYGGF4 (PID1) overexpression-induced insulin resistance through increasing phosphorylation of IRS-1 and AKT. J Bioenerg Biomembr 44(3):357–363PubMedCrossRefGoogle Scholar
- 35.Yamada M, Kaibori M, Tanaka H, Habara K, Hijikawa T, Tanaka Y, Oishi M, Okumura T, Nishizawa M, Kwon AH (2012) Alpha-lipoic acid prevents the induction of iNOS gene expression through destabilization of its mrna in proinflammatory cytokine-stimulated hepatocytes. Dig Dis Sci 57(4):943–951PubMedCrossRefGoogle Scholar
- 36.Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating amp-activated protein kinase. Nat Med 8(11):1288–1295PubMedCrossRefGoogle Scholar
- 37.Yu S, Zhang Y, Li MZ, Xu H, Wang Q, Song J, Lin P, Zhang L, Liu Q, Huang QX, Wang K, Hou WK (2012) Chemerin and apelin are positively correlated with inflammation in obese type 2 diabetic patients. Chin Med J (Engl) 125(19):3440–3444Google Scholar