Docosahexaenoic Acid and Its Role in G-Protein-Coupled Receptor 120 Activation in Children Affected by Nonalcoholic Fatty Liver Disease.

C. Della Corte, A. Mosca, A. Ionata, V. Nobili
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引用次数: 9

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of chronic liver disease in children and adults. Recently, therapeutic supplementation with docosahexaenoic acid (DHA) showed an anti-inflammatory and insulin-sensitizing effect in children with NAFLD. The anti-inflammatory effects of DHA depend on its ability to alter phospholipid composition of the cell membrane, to disrupt lipid rafts and to hamper the transcriptional activity of nuclear factor-x03BA;B that controls the expression of proinflammatory cytokines. These effects of DHA are due to the interaction with the G-protein-coupled receptor 120 (GRP120), a lipid-sensing receptor highly expressed in activated macrophages. In fact, DHA may activate GPR120 expression in macrophages causing anti-inflammatory effects, and insulin-sensitizing and antidiabetic effects in vivo. Recently, it has been shown that GPR120 is also expressed by the Kupffer cells of the liver. A diet low in n-3 polyunsaturated fatty acids, as well as the presence of genetic factors, may induce a reduction in the GRP120 signal and the activation of Kupffer cells and inflammation during NAFLD. Therefore, it is conceivable that DHA/GRP120 may play a key role in slowing the progression of liver damage in patients with NAFLD.
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二十二碳六烯酸及其在非酒精性脂肪肝患儿g蛋白偶联受体120激活中的作用
非酒精性脂肪性肝病(NAFLD)是儿童和成人慢性肝病最重要的病因之一。最近,治疗性补充二十二碳六烯酸(DHA)显示出对NAFLD儿童的抗炎和胰岛素增敏作用。DHA的抗炎作用取决于其改变细胞膜磷脂组成的能力,破坏脂筏和阻碍核因子x03ba;B的转录活性,核因子x03ba;B控制促炎细胞因子的表达。DHA的这些作用是由于与g蛋白偶联受体120 (GRP120)的相互作用,GRP120是一种在活化的巨噬细胞中高度表达的脂感受体。事实上,DHA可能激活巨噬细胞中GPR120的表达,从而在体内产生抗炎作用、胰岛素增敏和降糖作用。最近有研究表明,GPR120也可在肝脏库普弗细胞中表达。低n-3多不饱和脂肪酸的饮食,以及遗传因素的存在,可能导致NAFLD期间GRP120信号的减少,Kupffer细胞的激活和炎症。因此,可以想象DHA/GRP120可能在减缓NAFLD患者肝损伤进展中发挥关键作用。
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