Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.
Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.
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DOI：
10.1371/journal.pone.0043056
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Kita Y;Takamura T;Misu H;Ota T;Kurita S;Takeshita Y;Uno M;Matsuzawa-Nagata N;Kato K;Ando H;Fujimura A;Hayashi K;Kimura T;Ni Y;Otoda T;Miyamoto K;Zen Y;Nakanuma Y;Kaneko S
非酒精性脂肪性肝炎（NASH）的最佳治疗方法尚未确定，特别是对于无糖尿病的个体。我们在非糖尿病NASH小鼠模型中研究了二甲双胍（通常用于治疗2型糖尿病患者）对肝脏病理学的影响。对8周龄C57 BL/6小鼠喂食蛋氨酸和胆碱缺乏加高脂肪（MCD+HF）饲料（含或不含0.1%二甲双胍）8周。二甲双胍联合用药显著降低空腹血糖水平，但不影响葡萄糖耐量或外周胰岛素敏感性。二甲双胍可改善MCD+HF饲料诱导的肝脂肪变性、炎症和纤维化。此外，二甲双胍在实验性NASH发生后给药时可显著逆转肝脏脂肪变性和炎症。这些组织学变化伴随着肝脏甘油三酯含量降低，抑制肝星状细胞活化，以及参与脂肪酸代谢，炎症和纤维化的基因下调。二甲双胍在实验性非糖尿病模型中预防和逆转NASH的脂肪变性和炎症，而不影响外周胰岛素抵抗。
Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF) diet with or without 0.1% metformin for 8 weeks. Co-administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH. These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis. Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance.
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影响因子：
7.7
作者：
Basu, Rita;Shah, Pankaj;Rizza, Robert A.
通讯作者：
Rizza, Robert A.
影响因子：
3.3
作者：
CLARKE, SD
通讯作者：
CLARKE, SD
影响因子：
29.4
作者：
Aithal, Guruprasad P.;Thomas, James A.;Weeber, Jonathan
通讯作者：
Weeber, Jonathan
影响因子：
7.7
作者：
Marchesini, G;Brizi, M;Melchionda, N
通讯作者：
Melchionda, N
影响因子：
16.2
作者：
Hamaguchi, Erika;Takamura, Toshinari;Kaneko, Shuichi
通讯作者：
Kaneko, Shuichi