Dissipating excess energy stored in the liver is a potential treatment strategy for diabetes associated with obesity
Dissipating excess energy stored in the liver is a potential treatment strategy for diabetes associated with obesity
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DOI：
10.2337/diabetes.54.2.322
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发表时间：
2005-02-01
期刊：
影响因子：
7.7
通讯作者：
Oka, Y
中科院分区：
文献类型：
--
作者：
Ishigaki, Y;Katagiri, H;Oka, Y
为了检验消除肝脏中的过剩能量是否是治疗高脂饮食诱导的代谢紊乱的一种可能的方法，我们使用腺病毒载体在高脂饮食诱导的糖尿病和肥胖小鼠以及标准饮食喂养的瘦小鼠的肝脏中表达了解偶联蛋白-1(UCP1)。一旦糖尿病合并肥胖，肝脏UCP1的表达增加能量消耗，减轻体重，减少肝脏和脂肪组织中的脂肪，从而显著改善胰岛素抵抗，从而导致糖尿病和血脂异常。肝脏中脂质合成和葡萄糖产生的酶的表达减少以及AMP激活的激酶的激活似乎有助于这些改善。肝脏UCP1的表达也逆转了高脂饮食诱导的吞噬功能亢进和下丘脑瘦素抵抗，以及肌肉中的胰岛素抵抗。相比之下，有趣的是，在标准饮食喂养的瘦小鼠中，肝脏UCP1的表达并没有显著影响能量消耗或肝脏ATP含量。此外，没有观察到血糖水平、体重或肥胖的变化。这些发现表明，肝脏中的异位UCP1在不影响所需能量的情况下分散了多余的能量，并对瘦小鼠产生了最小的代谢影响。因此，UCP1在肝脏中的表达增强是治疗代谢综合征的新的潜在靶点。
For examining whether dissipating excess energy in the liver is a possible therapeutic approach to high-fat diet-induced metabolic disorders, uncoupling protein-1 (UCP1) was expressed in murine liver using adenoviral vectors in mice with high-fat diet-induced diabetes and obesity, and in standard diet-fed lean mice. Once diabetes with obesity developed, hepatic UCP1 expression increased energy expenditure, decreased body weight, and reduced fat in the liver and adipose tissues, resulting in markedly improved insulin resistance and, thus, diabetes and dyslipidemia. Decreased expressions of enzymes for lipid synthesis and glucose production and activation of AMP-activated kinase in the liver seem to contribute to these improvements. Hepatic UCP1 expression also reversed high-fat diet-induced hyperphagia and hypothalamic leptin resistance, as well as insulin resistance in muscle. In contrast, intriguingly, in standard diet-fed lean mice, hepatic UCP1 expression did not significantly affect energy expenditure or hepatic ATP contents. Furthermore, no alterations in blood glucose levels, body weight, or adiposity were observed. These findings suggest that ectopic UCP1 in the liver dissipates surplus energy without affecting required energy and exerts minimal metabolic effects in lean mice. Thus, enhanced UCP1 expression in the liver is a new potential therapeutic target for the metabolic syndrome.