Treatment with resistin ASO normalized plasma resistin levels in HF-fed mice. (A) Experimental design for treatment with resistin ASO and clamp studies. Mice on HF diet for 3 weeks received an i.p. injection of resistin ASO (RsASO) or control ASO (ConASO) 7 and 3 days before the insulin-clamp studies. Intravenous catheters were inserted into the jugular vein 3 days before the clamp procedure. (B) Plasma insulin levels at the end of insulin clamp. Insulin levels were similar in all experimental groups. (C) Plasma resistin levels. Circulating resistin levels are significantly increased in mice on HF diet (black bar) as compared with mice on SC (white bar). Treatment with resistin ASO significantly decreased circulating resistin levels to those of SC-fed mice. Finally, infusion of recombinant mouse resistin acutely restored circulating resistin levels (HF + RsASO + i.v. Rs) to those observed in the HF-fed mice treated with control ASO. (D) Increased liver TGs with HF diet. Hepatic TG content was increased twofold by HF diet, whereas treatment with resistin ASO or acute infusion of recombinant resistin did not significantly altered hepatic TG levels. *P < 0.01 vs. SC group; #P < 0.01 vs. HF + ConASO; P < 0.01 vs. HF + RsASO. ww, wet weight.