Abstract
Tumor necrosis factor α (TNFα) is an adipokine, whose increase is known to suppress the expression and secretion of adiponectin in adipocytes. Resveratrol has been ever reported to recover the suppression of adiponectin by TNFα, but the underlying mechanism remains poorly understood. In this study, we validated the roles of resveratrol in the inhibition of the adiponectin by TNFα in 3T3-L1 cells. Exposure to TNFα for 24 h inhibited adiponectin synthesis and secretion, but the inhibitions were partially recovered by resveratrol treatment in 3T3-L1 adipocytes. Furthermore, we found that resveratrol improved the expression of adiponectin by the increase of PPARγ DNA-binding activity. Our results suggest that resveratrol may attenuate the inhibition of adiponectin expression by TNFα via activation of PPARγ, thereby possibly improving insulin resistance. However, significant preventive effects of resveratrol were only observed when it was administrated before TNFα increase, limiting its use as preventive strategy for insulin resistance.
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Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946
Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein acrp30 enhances hepatic insulin action. Nat Med 7:947–953
Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98:2005–2010
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 8:1288–1295
Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, Funahashi T, Walsh K (2004) Adiponectin stimulates angiogenesis by promoting cross-talk between amp-activated protein kinase and akt signaling in endothelial cells. J Biol Chem 279:1304–1309
Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ (2003) Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 278:45021–45026
Hu E, Liang P, Spiegelman BM (1996) Adipoq is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271:10697–10703
Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415
Hotamisligil GS, Spiegelman BM (1994) Tumor necrosis factor alpha: a key component of the obesity–diabetes link. Diabetes 43:1271–1278
Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y (2001) Ppargamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:2094–2099
Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y (2002) Diet-induced insulin resistance in mice lacking adiponectin/acrp30. Nat Med 8:731–737
You M, Considine RV, Leone TC, Kelly DP, Crabb DW (2005) Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice. Hepatology 42:568–577
Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y (1996) Enhanced expression of pai-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med 2:800–803
Peraldi P, Spiegelman B (1998) TNF-alpha and insulin resistance: summary and future prospects. Mol Cell Biochem 182:169–175
Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV (1996) Leptin: the tale of an obesity gene. Diabetes 45:1455–1462
Ahn J, Lee H, Kim S, Ha T (2007) Resveratrol inhibits TNF-alpha-induced changes of adipokines in 3T3-L1 adipocytes. Biochem Biophys Res Commun 364:972–977
Kadowaki T, Yamauchi T (2005) Adiponectin and adiponectin receptors. Endocr Rev 26:439–451
Yang WS, Jeng CY, Wu TJ, Tanaka S, Funahashi T, Matsuzawa Y, Wang JP, Chen CL, Tai TY, Chuang LM (2002) Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 25:376–380
Cawthorn WP, Sethi JK (2008) TNF-alpha and adipocyte biology. FEBS Lett 582:117–131
Acknowledgments
This work was supported by Science and Technology Programs to Hai-Yan Zhang (2010225032) and Zhen-Xian Du (2009225012) from Department of Science and Technology of Liaoning Province, and colleges and universities research programs to Hai-Yan Zhang (2009A765) from Department of Education of Liaoning province.
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Zhang, HY., Du, ZX. & Meng, X. Resveratrol prevents TNFα-induced suppression of adiponectin expression via PPARγ activation in 3T3-L1 adipocytes. Clin Exp Med 13, 193–199 (2013). https://doi.org/10.1007/s10238-012-0189-2
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DOI: https://doi.org/10.1007/s10238-012-0189-2