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首页> 外文期刊>Endocrinology >Curcumin eliminates leptin's effects on hepatic stellate cell activation via interrupting leptin signaling.
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Curcumin eliminates leptin's effects on hepatic stellate cell activation via interrupting leptin signaling.

机译：姜黄素可通过中断瘦素信号传导消除瘦素对肝星状细胞活化的影响。

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摘要

Nonalcoholic steatohepatitis (NASH) is commonly found in patients with obesity and is often accompanied with abnormally elevated levels of plasma leptin, i.e. hyperleptinemia. A relatively high population of NASH patients develops hepatic fibrosis, even cirrhosis. Hepatic stellate cells (HSCs) are the major effector cells during liver fibrogenesis and could be activated by leptin. The antioxidant curcumin, a phytochemical from turmeric, has been shown to suppress HSC activation in vitro and in vivo. This project is to evaluate the effect of curcumin on leptin-induced HSC activation and to elucidate the underlying mechanisms. We hypothesize that curcumin abrogates the stimulatory effect of leptin on HSC activation by interrupting leptin signaling and attenuating leptin-induced oxidative stress. Curcumin eliminates the stimulatory effects of leptin on regulating expression of genes closely relevant to HSC activation. Curcumin interrupts leptin signaling by reducing phosphorylation levels of leptin receptor (Ob-R) and its downstream intermediators. In addition, curcumin suppresses gene expression of Ob-R in HSCs, which requires the activation of endogenous peroxisome proliferator-activated receptor-gamma and de novo synthesis of glutathione. In conclusion, our results demonstrate that curcumin abrogates the stimulatory effect of leptin on HSC activation in vitro by reducing the phosphorylation level of Ob-R, stimulating peroxisome proliferator-activated receptor-gamma activity, and attenuating oxidative stress, leading to the suppression of Ob-R gene expression and interruption of leptin signaling. These results provide novel insights into therapeutic mechanisms of curcumin in inhibiting HSC activation and intervening liver fibrogenesis associated with hyperleptinemia in NASH patients.
机译：非酒精性脂肪性肝炎（NASH）通常在肥胖患者中发现，并经常伴有血浆瘦素水平异常升高，即高瘦素血症。相对较多的NASH患者会发展为肝纤维化，甚至肝硬化。肝星状细胞（HSC）是肝纤维化过程中的主要效应细胞，可以被瘦素激活。抗氧化剂姜黄素是姜黄的一种植物化学物质，已显示出在体外和体内抑制HSC活化的作用。该项目旨在评估姜黄素对瘦素诱导的HSC活化的影响并阐明其潜在机制。我们假设姜黄素通过中断瘦素信号传导和减弱瘦素诱导的氧化应激而消除了瘦素对HSC激活的刺激作用。姜黄素消除了瘦素对调节与HSC激活密切相关的基因表达的刺激作用。姜黄素通过降低瘦素受体（Ob-R）及其下游中介物的磷酸化水平来中断瘦素信号传导。另外，姜黄素抑制HSC中Ob-R的基因表达，这需要激活内源性过氧化物酶体增殖物激活的受体-γ和从头合成谷胱甘肽。总之，我们的结果表明姜黄素通过降低Ob-R的磷酸化水平，刺激过氧化物酶体增殖物激活的受体-γ活性和减弱氧化应激，从而消除了瘦素对体外HSC激活的刺激作用，从而导致对Ob的抑制-R基因表达和瘦素信号传导中断。这些结果为姜黄素抑制NASH患者高脂蛋白血症相关的HSC活化和介入肝纤维发生提供了新的见解。

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