Hepatocyte growth factor alleviates hepatic insulin resistance and lipid accumulation in high-fat diet-fed mice.
Hepatocyte growth factor alleviates hepatic insulin resistance and lipid accumulation in high-fat diet-fed mice.
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肝细胞生长因子减轻高脂饮食小鼠的肝脏胰岛素抵抗和脂质积累
DOI：
10.1111/jdi.12904
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发表时间：
2019-03
影响因子：
3.2
通讯作者：
Zhu D
中科院分区：
文献类型：
--
作者：
Jing Y;Sun Q;Xiong X;Meng R;Tang S;Cao S;Bi Y;Zhu D
2型糖尿病常伴有脂肪肝。肝脏内的脂质积聚被认为是胰岛素抵抗的危险因素之一。肝细胞生长因子（HGF）被用于治疗肝功能障碍，但其对肝脏脂质代谢的影响及其机制尚不完全清楚。雄性C57 BL/6小鼠用高脂饮食诱导12周，然后用HGF或溶剂盐水处理4周。计算空腹血糖、空腹胰岛素水平及稳态模型胰岛素抵抗评估值，评价胰岛素敏感性。还测量了生化血浆参数，以评估HGF对脂质蓄积的影响。此外，在棕榈酸处理的HepG 2细胞和高脂饮食小鼠中评价了脂质代谢途径中的基因。肝细胞生长因子治疗显著降低空腹血糖水平，肝甘油三酯和胆固醇含量。此外，HGF调节固醇调节元件结合蛋白-1c/脂肪酸合酶、过氧化物酶增殖物激活受体-α和上游核受体（如法尼醇X受体和小异源二聚体伴侣）的表达水平。此外，c-Met抑制剂可以部分逆转HGF的作用。肝细胞生长因子治疗可通过调节脂质代谢改善肝脏胰岛素抵抗和脂肪变性。这些作用可能通过法尼醇X受体-小异源二聚体伴侣轴依赖性转录活性发生。
Type 2 diabetes mellitus is frequently accompanied by fatty liver disease. Lipid accumulation within the liver is considered as one of the risk factors for insulin resistance. Hepatocyte growth factor (HGF) is used to treat liver dysfunction; however, the effect and mechanism of HGF on hepatic lipid metabolism are still not fully understood. Male C57BL/6 mice were induced with a high‐fat diet for 12 weeks, followed by a 4‐week treatment of HGF or vehicle saline. The levels of fasting blood glucose, fasting insulin and homeostatic model assessment of insulin resistance were calculated for insulin sensitivity. Biochemical plasma parameters were also measured to assess the effect of HGF on lipid accumulation. Additionally, genes in the lipid metabolism pathway were evaluated in palmitic acid‐treated HepG2 cells and high‐fat diet mice. HGF treatment significantly decreased the levels of fasting blood glucose, hepatic triglyceride and cholesterol contents. Additionally, HGF‐regulated expression levels of sterol regulatory element‐binding protein‐1c/fatty acid synthase, peroxidase proliferator‐activated receptor‐α, and upstream nuclear receptors, such as farnesoid X receptor and small heterodimer partner. Furthermore, c‐Met inhibitor could partially reverse the effects of HGF. HGF treatment can ameliorate hepatic insulin resistance and steatosis through regulation of lipid metabolism. These effects might occur through farnesoid X receptor–small heterodimer partner axis‐dependent transcriptional activity.
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影响因子：
4.6
作者：
Muratsu J;Iwabayashi M;Sanada F;Taniyama Y;Otsu R;Rakugi H;Morishita R
通讯作者：
Morishita R
DOI：
10.2183/pjab.86.588
发表时间：
2010
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Nakamura T;Mizuno S
通讯作者：
Mizuno S
影响因子：
25.7
作者：
Sugimoto, T;Yamashita, S;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
4.8
作者：
Bertola, Adeline;Bonnafous, Stephanie;Gual, Philippe
通讯作者：
Gual, Philippe
影响因子：
1.9
作者：
Frederico, Marisa J. S.;Vitto, Marcelo F.;De Souza, Claudio T.
通讯作者：
De Souza, Claudio T.