Curcumin Inhibits Hepatic Protein-Tyrosine Phosphatase 1B and Prevents Hypertriglyceridemia and Hepatic Steatosis in Fructose-Fed Rats
Curcumin Inhibits Hepatic Protein-Tyrosine Phosphatase 1B and Prevents Hypertriglyceridemia and Hepatic Steatosis in Fructose-Fed Rats
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姜黄素抑制肝蛋白酪氨酸磷酸酶 1B，预防果糖喂养大鼠的高甘油三酯血症和肝脂肪变性
DOI：
10.1002/hep.23524
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发表时间：
2010-05-01
期刊：
影响因子：
13.5
通讯作者：
Hu, Qing-Hua
中科院分区：
文献类型：
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作者：
Li, Jian-Mei;Li, Yu-Cheng;Hu, Qing-Hua
高果糖摄入是胰岛素抵抗或瘦素抵抗引起肝脂肪变性的重要因素。本研究观察了姜黄素对果糖诱导的大鼠高甘油三酯血症和肝脂肪变性的影响，并探讨其预防机制。姜黄素降低果糖喂养大鼠的血清胰岛素和瘦素水平。该化合物可以增加胰岛素受体和胰岛素受体底物1的磷酸化，从而增强果糖喂养大鼠肝脏中Akt和细胞外信号调节激酶1/2（ERK 1/2）的激活。此外，姜黄素增加磷酸化肝janus激活激酶信号转导2，随后也刺激Alct和ERK 1/2激活在这个模型中。姜黄素对瘦素信号传导的抑制过度刺激长型瘦素受体和信号转导子和转录激活子3的酪氨酸1138磷酸化导致果糖喂养大鼠肝脏中细胞因子信号传导抑制子3的下调。因此，姜黄素改善胰岛素和瘦素信号转导和随后升高过氧化物酶体增殖物激活受体cc表达导致极低密度脂蛋白过度产生和甘油三酯过度合成减少。此外，在果糖喂养的大鼠中观察到与胰岛素和瘦素信号缺陷相关的肝蛋白酪氨酸磷酸酶1B（PTP 1B）的过度表达和过度活性。此外，发现姜黄素在该模型中显著降低肝脏PTP 1B表达和活性。结论：我们的数据表明，姜黄素对果糖诱导的高甘油三酯血症和肝脂肪变性的保护机制是其对PTP 1B的抑制，并随后改善大鼠肝脏中的胰岛素和瘦素敏感性。这种PTP 1B抑制特性可能是姜黄素治疗由肝胰岛素和瘦素抵抗驱动的果糖诱导的肝脂肪变性的有前途的治疗策略。（《肝脏学》2010年;51：1555-1566）
High consumption of dietary fructose is an important contributory factor in the development of hepatic steatosis in insulin or leptin resistance. We investigated the effects of curcumin on fructose-induced hypertriglyceridemia and liver steatosis and explored its preventive mechanisms in rats. Curcumin reduced serum insulin and leptin levels in fructose-fed rats. This compound could increase phosphorylation of insulin receptor and insulin receptor substrate 1 to enhance Akt and extracellular signal-regulated kinase1/2 (ERK1/2) activation in the liver of fructose-fed rats. Moreover, curcumin increased phosphorylation of hepatic janus-activated kinase-signal transducer 2 and subsequently also stimulated Alct and ERK1/2 activation in this model. Suppression of curcumin on leptin signaling overstimulation in tyrosine1138 phosphorylation of the long form of leptin receptor and signal transducer and activator of transcription 3 resulted in down-regulation of suppressor of cytokine signaling 3 in the liver of fructose-fed rats. Thus, improvement of insulin and leptin signaling transduction and subsequently elevation of peroxisome proliferator-activated receptor cc expression by curcumin led to reduction of very-low-density lipoprotein overproduction and triglyceride hypersynthesis. Furthermore, overexpression and hyperactivity of hepatic protein tyrosine phosphatase 1B (PTP1B) associated with defective insulin and leptin signaling were observed in fructose-fed rats. Additionally, curcumin was found to significantly reduce hepatic PTP1B expression and activity in this model. Conclusion: Our data indicate that the mechanisms by which curcumin protects against fructose-induced hypertriglyceridemia and hepatic steatosis are its inhibition on PTP1B and subsequently improvement of insulin and leptin sensitivity in the liver of rats. This PTP1B inhibitory property may be a promising therapeutic strategy for curcumin to treat fructose-induced hepatic steatosis driven by hepatic insulin and leptin resistance. (HEPATOLOGY 2010;51:1555-1566.)