Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet
Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet
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DOI：
10.1194/jlr.m800042-jlr200
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发表时间：
2008-05-01
影响因子：
6.5
通讯作者：
Green, Richard M.
中科院分区：
文献类型：
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作者：
Rinella, Mary E.;Elias, Marc S.;Green, Richard M.
蛋氨酸胆碱缺乏（MCD）饮食会导致类似于人类非酒精性脂肪性肝炎（NASH）的肝损伤。本研究的目的是确定 MCD 诱导胰岛素抵抗 db/db 和胰岛素敏感 db/m 小鼠脂肪变性的机制。与 MCD 喂养的 db/m 小鼠相比，MCD 喂养的 db/db 小鼠出现更多的肝脏脂肪变性并保留更多的胰岛素抵抗。 MCD 喂养可减少皮下脂肪和性腺脂肪：db/db 小鼠的性腺脂肪减少 23%，db/m 小鼠的性腺脂肪减少 90%。 db/db 小鼠的体重减轻减弱，仅为 13%，而 MCD 喂养的 db/db 和 db/m 小鼠的体重减轻分别为 35%。两种菌株的肝脏脂肪酸转运蛋白均上调，并且肝脏对 [C-14] 油酸的摄取增加：MCD 喂养 4 周后，db/m 小鼠增加了 3 倍（P < 0.001），db/db 小鼠增加了 2 倍（P < 0.01）。在这两种小鼠品系中，MCD 饮食减少了甘油三酯的分泌，并下调了参与甘油三酯合成的基因。因此，增加脂肪酸摄取和减少 VLDL 分泌代表了 MCD 饮食促进该模型中肝内脂质积累的两个重要机制。给糖尿病啮齿动物喂食 MCD 饮食拓宽了该模型在人类 NASH 研究中的适用性。
The methionine choline-deficient (MCD) diet results in liver injury similar to human nonalcoholic steatohepatitis (NASH). The aims of this study were to define mechanisms of MCD-induced steatosis in insulin-resistant db/db and insulin-sensitive db/m mice. MCD-fed db/db mice developed more hepatic steatosis and retained more insulin resistance than MCD-fed db/m mice. Both subcutaneous and gonadal fat were reduced by MCD feeding: gonadal fat decreased by 23% in db/db mice and by 90% in db/m mice. Weight loss was attenuated in the db/db mice, being only 13% compared With 35% in MCD-fed db/db and db/m mice, respectively. Both strains had upregulation of hepatic fatty acid transport proteins as well as increased hepatic uptake of [C-14] oleic acid: 3-fold in db/m mice (P < 0.001) and 2-fold in db/db mice (P < 0.01) after 4 weeks of MCD feeding. In both murine strains, the MCD diet reduced triglyceride secretion and downregulated genes involved in triglyceride synthesis. Therefore, increased fatty acid uptake and decreased VLDL secretion represent two important mechanisms by Which the MCD diet promotes intrahepatic lipid accumulation in this model. Feeding the MCD diet to diabetic rodents broadens the applicability of this model for the study of human NASH.