Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice.
Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice.
复制标题
DOI：
10.1016/j.toxrep.2015.11.003
复制
发表时间：
2016
影响因子：
--
通讯作者：
Matsumoto A
中科院分区：
文献类型：
--
作者：
Iizuka Y;Kim H;Nakasatomi M;Izawa T;Hirako S;Matsumoto A
吡格列酮是一种噻唑烷二酮 (TZD)，广泛用作胰岛素增敏剂，用于治疗 2 型糖尿病。然而，在接受 TZD 治疗的患者中经常观察到体重增加。鱼油可改善脂质代谢功能障碍和肥胖。在这项研究中，我们通过吡格列酮和鱼油联合治疗 2 型糖尿病 KK 小鼠，证明了吡格列酮给药可抑制体重增加。雄性 KK 小鼠被喂食实验饮食 8 周。在红花油（SO）、红花油/低剂量吡格列酮（S/PL）和红花油/高剂量吡格列酮（S/PH）饮食中，20%的热量分别由含有0%、0.006%或0.012%（wt/wt）吡格列酮的红花油提供。在鱼油 (FO)、鱼油/低剂量吡格列酮 (F/PL) 和鱼油/高剂量吡格列酮 (F/PH) 饮食中，20% 的热量由鱼油和红花油的混合物提供。 S/PL和S/PH组中观察到体重和皮下脂肪量增加；然而，含有鱼油的饮食被发现可以改善这些变化。鱼油喂养组的肝脏脂肪生成酶 mRNA 水平显着降低。这些发现表明，吡格列酮和鱼油的组合通过鱼油介导的肝脏从头脂肪生成抑制作用，减少皮下脂肪积累，改善吡格列酮引起的体重增加。
Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO), safflower oil/low-dose pioglitazone (S/PL), and safflower oil/high-dose pioglitazone (S/PH) diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt) pioglitazone, respectively. In fish oil (FO), fish oil/low-dose pioglitazone (F/PL), and fish oil/high-dose pioglitazone (F/PH) diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups; however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis.