Humoral Regulation of Resistin Expression in 3T3-L1 and Mouse Adipose Cells

Humoral Regulation of Resistin Expression in 3T3-L1 and Mouse Adipose Cells Nobuhiro Shojima 1 , Hideyuki Sakoda 2 , Takehide Ogihara 1 , Midori Fujishiro 1 , Hideki Katagiri 3 , Motonobu Anai 2 , Yukiko Onishi 2 , Hiraku Ono 2 , Kouichi Inukai 4 , Miho Abe 1 , Yasushi Fukushima 1 , Masatoshi Kikuchi 2 , Yoshitomo Oka 3 and Tomoichiro Asano 1 1 Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 2 Institute for Adult Disease, Asahi Life Foundation, Tokyo, Japan 3 Department of Internal Medicine, University of Tohoku, Sendai, Japan 4 Fourth Department of Internal Medicine, Saitama Medical School, Saitama, Japan Abstract Resistin is a hormone secreted by adipocytes that acts on skeletal muscle myocytes, hepatocytes, and adipocytes themselves, reducing their sensitivity to insulin. In the present study, we investigated how the expression of resistin is affected by glucose and by mediators known to affect insulin sensitivity, including insulin, dexamethasone, tumor necrosis factor-α (TNF-α), epinephrine, and somatropin. We found that resistin expression in 3T3-L1 adipocytes was significantly upregulated by high glucose concentrations and was suppressed by insulin. Dexamethasone increased expression of both resistin mRNA and protein 2.5- to 3.5-fold in 3T3-L1 adipocytes and by ∼70% in white adipose tissue from mice. In contrast, treatment with troglitazone, a thiazolidinedione antihyperglycemic agent, or TNF-α suppressed resistin expression by ∼80%. Epinephrine and somatropin were both moderately inhibitory, reducing expression of both the transcript and the protein by 30–50% in 3T3-L1 adipocytes. Taken together, these data make it clear that resistin expression is regulated by a variety of hormones and that cytokines are related to glucose metabolism. Furthermore, they suggest that these factors affect insulin sensitivity and fat tissue mass in part by altering the expression and eventual secretion of resistin from adipose cells. Footnotes Address correspondence and reprint requests to Asano Tomoichiro, Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. E-mail: asano-tky{at}umin.ac.jp . Received for publication 22 October 2001 and accepted in revised form 11 March 2002. DMEM, Dulbecco’s modified Eagle’s medium; PPAR, peroxisome proliferator-activated receptor; TNF-α, tumor necrosis factor α. DIABETES