Duodenal-Jejunal Bypass Surgery Suppresses Hepatic De Novo Lipogenesis and Alleviates Liver Fat Accumulation in a Diabetic Rat Model
Duodenal-Jejunal Bypass Surgery Suppresses Hepatic De Novo Lipogenesis and Alleviates Liver Fat Accumulation in a Diabetic Rat Model
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十二指肠空肠绕道手术抑制糖尿病大鼠模型中肝脏从头脂肪生成并减轻肝脏脂肪堆积
DOI：
10.1007/s11695-014-1308-9
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发表时间：
2014-12-01
期刊：
影响因子：
2.9
通讯作者：
Hu, Sanyuan
中科院分区：
文献类型：
--
作者：
Han, Haifeng;Hu, Chunxiao;Hu, Sanyuan
背景：十二指肠-空肠搭桥术(DJB)可使2型糖尿病(T2 DM)迅速持久缓解，但其内在机制尚不清楚。最近的研究表明，改善肝脏胰岛素抵抗和胰岛素信号转导可能有助于DJB后糖尿病的控制。鉴于肝脏肥胖在肝脏胰岛素抵抗中的重要作用，本研究旨在观察DJB对高脂饮食(HFD)和小剂量链脲佐菌素(STZ)诱导的T2 DM大鼠血糖稳态和肝脏脂肪蓄积的影响。方法将40只成年雄性糖尿病大鼠随机分为假手术组和DJB组。在指定的时间点测量体重、卡路里摄入量、激素水平、血糖和血脂参数。分别于术后2周和8周检测大鼠肝脏甘油三酯(TG)含量和糖调节元件结合蛋白-1(SREBP-1)、碳水化合物反应元件结合蛋白(ChREBP)、脂肪酸合成酶(FAS)和乙酰辅酶A羧基酶(ACC)的蛋白水平。结果与Sham组相比，DJB组大鼠的血糖稳态和胰岛素敏感性显著改善，且与体重减轻和热量限制无关。DJB组大鼠术后8周肝脏TG含量降低，肝脏SREBP-1、ChREBP、ACC和Fas含量降低。结论DJB可减轻肝脏脂肪堆积，下调参与肝脏新生脂肪生成的关键转录调节因子和酶的表达，可能有助于改善DJB后肝脏的胰岛素敏感性和血糖稳态。
Background Duodenal-jejunal bypass (DJB) surgery can induce rapid and durable remission of type 2 diabetes mellitus (T2DM), but the intrinsic mechanisms remain to be elucidated. Recent studies indicated that improved hepatic insulin resistance and insulin signaling transduction might contribute to the diabetic control after DJB. Given the important role of liver adiposity in hepatic insulin resistance, this study was aimed at investigating the effects of DJB on glucose homeostasis and liver fat accumulation in a T2DM rat model induced by high-fat diet (HFD) and small dose of streptozotocin (STZ).Methods Forty adult male diabetic rats induced by HFD and small dose of STZ were randomly assigned to sham and DJB groups. Body weight, calorie intake, hormone levels, glucose, and lipid parameters were measured at indicated time points. Subsequently, hepatic triglycerides (TG) content and the protein levels of sterol regulatory element binding protein-1 (SREBP-1), carbohydrate response element binding protein (ChREBP), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were evaluated at 2 and 8 weeks postoperatively.Results Compared with sham group, DJB induced rapid and significant improvements in glucose homeostasis and insulin sensitivity independently of weight loss and calorie restriction. The DJB-operated rats exhibited lower liver TG content and decreased hepatic SREBP-1, ChREBP, ACC, and FAS at 8 weeks postoperatively.Conclusions DJB alleviated hepatic fat accumulation and downregulated the key transcriptional regulators and enzymes involved in hepatic de novo lipogenesis, which might contribute to improved hepatic insulin sensitivity and glucose homeostasis after DJB.