Role of white adipose lipolysis in the development of NASH induced by methionine- and choline-deficient diet.
Role of white adipose lipolysis in the development of NASH induced by methionine- and choline-deficient diet.
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DOI：
10.1016/j.bbalip.2014.08.015
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Gonzalez FJ
中科院分区：
文献类型：
--
作者：
Tanaka N;Takahashi S;Fang ZZ;Matsubara T;Krausz KW;Qu A;Gonzalez FJ
蛋氨酸和胆碱缺乏饮食（MCD）是啮齿类动物非酒精性脂肪性肝炎（NASH）的模型。然而，饮食蛋氨酸/胆碱缺乏导致NASH发展的机制仍不确定。为了阐明与MCD-NASH相关的早期代谢变化，使用MCD和对照饲料处理3天和1周的小鼠进行了血清代谢组学分析，结果显示MCD处理后油酸和亚油酸显著增加。这些增加与体重和白色脂肪组织（WAT）质量降低、脂肪敏感性脂肪酶磷酸化增加以及WAT中羧酸酯酶3和β2-肾上腺素能受体编码基因上调相关，表明脂肪细胞的脂解加速。MCD处理引起的血清脂肪酸和WAT变化可通过补充蛋氨酸逆转，在喂食蛋氨酸缺乏饲料（MD）的小鼠中检测到类似变化，从而证明饲料蛋氨酸缺乏可增强WAT中的脂解。MD治疗降低了血清中的葡萄糖并增加了成纤维细胞生长因子21，因此表现出与禁食反应相似的代谢表型。MCD和胆碱缺乏饮食（CD）治疗之间的比较表明，在CD诱导的肝脂肪变性中添加MD诱导的代谢改变（如WAT脂解）可促进肝损伤。总的来说，这些结果证明了饮食蛋氨酸缺乏和WAT脂解在MCD-NASH发展中的重要作用。
Methionine- and choline-deficient diet (MCD) is a model for nonalcoholic steatohepatitis (NASH) in rodents. However, the mechanism of NASH development by dietary methionine/choline deficiency remains undetermined. To elucidate the early metabolic changes associated with MCD-NASH, serum metabolomic analysis was performed using mice treated with MCD and control diet for three days and one week, revealing significant increases in oleic and linoleic acids after MCD treatment. These increases were correlated with reduced body weight and white adipose tissue (WAT) mass, increased phosphorylation of hormone-sensitive lipase, and up-regulation of genes encoding carboxylesterase 3 and β2-adrenergic receptor in WAT, indicating accelerated lipolysis in adipocytes. The changes in serum fatty acids and WAT by MCD treatment were reversed by methionine supplementation, and similar alterations were detected in mice fed a methionine-deficient diet (MD), thus demonstrating that dietary methionine deficiency enhances lipolysis in WAT. MD treatment decreased glucose and increased fibroblast growth factor 21 in serum, thus exhibiting a similar metabolic phenotype as the fasting response. Comparison between MCD and choline-deficient diet (CD) treatments suggested that the addition of MD-induced metabolic alterations, such as WAT lipolysis, to CD-induced hepatic steatosis promotes liver injury. Collectively, these results demonstrate an important role for dietary methionine deficiency and WAT lipolysis in the development of MCD-NASH.
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影响因子：
13.5
作者：
Ong, Kuok Teong;Mashek, Mara T.;Bu, So Young;Greenberg, Andrew S.;Mashek, Douglas G.
通讯作者：
Mashek, Douglas G.
影响因子：
7.7
作者：
Okazaki, Hiroaki;Igarashi, Masaki;Ishibashi, Shun
通讯作者：
Ishibashi, Shun
纳什（Nash）是一种炎症障碍：致病性，预后和治疗意义。
影响因子：
3.4
作者：
Farrell GC;van Rooyen D;Gan L;Chitturi S
通讯作者：
Chitturi S
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH
影响因子：
29
作者：
Idle, Jeffrey R.;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.