Hemin Improves Insulin Sensitivity and Lipid Metabolism in Cultured Hepatocytes and Mice Fed a High-Fat Diet.
Hemin Improves Insulin Sensitivity and Lipid Metabolism in Cultured Hepatocytes and Mice Fed a High-Fat Diet.
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氯化血红素可改善培养肝细胞和高脂饮食小鼠的胰岛素敏感性和脂质代谢
DOI：
10.3390/nu9080805
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发表时间：
2017-07-26
期刊：
影响因子：
5.9
通讯作者：
Zhai Q
中科院分区：
文献类型：
--
作者：
Luan Y;Zhang F;Cheng Y;Liu J;Huang R;Yan M;Wang Y;He Z;Lai H;Wang H;Ying H;Guo F;Zhai Q
血红蛋白是血红蛋白的分解产物。据报道，注射血红蛋白可改善多种遗传模型的脂质代谢和胰岛素敏感性。然而，食物中补充血红蛋白对脂质代谢和胰岛素敏感性的影响尚不清楚，血红蛋白是否直接影响细胞胰岛素敏感性尚不清楚。本研究表明，在胰岛素抵抗条件下，血红蛋白增强了胰岛素诱导的胰岛素受体、Akt、Gsk3β、fox01的磷酸化和fox01的细胞质易位。此外，血红素减少甘油三酯的积累，并增加棕榈酸诱导的原代肝细胞中游离脂肪酸的含量。口服hemin可降低高脂饮食雄性小鼠的体重、能量摄入、血糖和甘油三酯水平，改善胰岛素和葡萄糖耐量以及肝脏胰岛素信号传导和肝脏脂肪变性。此外，血红素处理降低了肝脏中参与脂肪生成调控、脂肪酸合成和储存的部分基因的mRNA和蛋白水平，增加了参与脂肪酸氧化的CPT1的mRNA水平和酶活性。这些数据表明，血红蛋白可以改善培养肝细胞和高脂饮食小鼠的脂质代谢和胰岛素敏感性，并显示食物血红蛋白对脂质和葡萄糖代谢的潜在有益作用。
Hemin is a breakdown product of hemoglobin. It has been reported that the injection of hemin improves lipid metabolism and insulin sensitivity in various genetic models. However, the effect of hemin supplementation in food on lipid metabolism and insulin sensitivity is still unclear, and whether hemin directly affects cellular insulin sensitivity is yet to be elucidated. Here we show that hemin enhances insulin-induced phosphorylation of insulin receptors, Akt, Gsk3β, FoxO1 and cytoplasmic translocation of FoxO1 in cultured primary hepatocytes under insulin-resistant conditions. Furthermore, hemin diminishes the accumulation of triglyceride and increases in free fatty acid content in primary hepatocytes induced by palmitate. Oral administration of hemin decreases body weight, energy intake, blood glucose and triglyceride levels, and improves insulin and glucose tolerance as well as hepatic insulin signaling and hepatic steatosis in male mice fed a high-fat diet. In addition, hemin treatment decreases the mRNA and protein levels of some hepatic genes involved in lipogenic regulation, fatty acid synthesis and storage, and increases the mRNA level and enzyme activity of CPT1 involved in fatty acid oxidation. These data demonstrate that hemin can improve lipid metabolism and insulin sensitivity in both cultured hepatocytes and mice fed a high-fat diet, and show the potential beneficial effects of hemin from food on lipid and glucose metabolism.
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