The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice
The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice
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DOI：
10.1172/jci200317797
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发表时间：
2003-07-01
影响因子：
15.9
通讯作者：
Cooper, GJS
中科院分区：
文献类型：
--
作者：
Xu, AM;Wang, Y;Cooper, GJS
脂联素最近被证明是治疗肥胖相关代谢综合征的有希望的候选药物。在小鼠体内补充重组脂联素可以降低高血糖，逆转胰岛素抵抗，并在不影响食物摄入量的情况下引起持续的体重减轻。在这里，我们报道了它在小鼠酒精性和非酒精性脂肪肝疾病中的潜在作用。脂联素循环浓度在长期食用高脂肪含乙醇食物后显著下降。将重组脂联素注入这些小鼠体内，可显著减轻肝肿大和脂肪变性（脂肪肝），并显著减轻炎症和血清丙氨酸转氨酶水平升高。这些治疗效果部分是由于脂联素能够增加肉毒碱棕榈酰基转移酶I的活性和增强肝脏脂肪酸氧化，同时降低脂肪酸合成的两个关键酶的活性，包括乙酰辅酶a羧化酶和脂肪酸合成酶。此外，脂联素治疗可以抑制肝脏产生tnf - α和血浆中这种促炎细胞因子的浓度。脂联素还能有效改善与非酒精性肥胖（ob/ob）小鼠相关的肝肿大、脂肪变性和丙氨酸转氨酶异常。这些结果证明了脂联素作用的新机制，并提示了脂联素及其激动剂在肝脏疾病治疗中的潜在临床应用。
Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.