来自美国哈佛大学医学院的科学家发现LNFPIII通过直接或间接控制代谢途径胞外信号调节激酶(Erk)-激活因子蛋白1(Ap1)通路减轻脂肪肝和胰岛素耐受。

-2012年11月《自然-医学》

中文翻译


【题目】聚糖LNFPIII通过直接或间接控制代谢途径减轻脂肪肝和胰岛素耐受

【译文】寄生虫表达宿主聚糖以抑制人类宿主的免疫反应。这种免疫调制机制的治疗潜能在控制与慢性炎症相关的代谢疾病方面尚不清楚。本研究证实了施予乳酰-N-岩藻五糖III (LNFPIII),一种在人乳中和寄生虫上发现的含LewisX免疫调制的聚糖,会提高饮食诱导的肥胖小鼠中的葡萄糖耐量及胰岛素敏感性。这种效应部分是通过增加由LNFPIII激活的巨噬细胞和树状细胞产生的白介素10的增加而介导的,白介素10的增加会减少白脂肪组织炎症并使得脂肪细胞的胰岛素反应变得敏感。与此同时,LNFPIII治疗会上调核受体亚家族1,H组,第四成员(Fxr-α,又称为Nr1h4),从而抑制肝脏中脂肪形成,防止脂肪肝发生。在信号水平,胞外信号调节激酶(Erk)-激活因子蛋白1(Ap1)通路似乎调控着LNFPIII对炎症和代谢通路的作用。 我们的结果表明LNFPIII可能提供了治疗代谢性疾病的新疗法。

英文原稿


[Title]: Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways

 [Authors]:Prerna Bhargava,1 Changlin Li,2 Kristopher J Stanya,1 David Jacobi,1, 3 Lingling Dai,1, 4 Sihao Liu,1 Matthew R Gangl,1 Donald A Harn2 & Chih-Hao Lee1

[Abstract]Parasitic worms express host-like glycans to attenuate the immune response of human hosts. The therapeutic potential of this immunomodulatory mechanism in controlling the metabolic dysfunction that is associated with chronic inflammation remains unexplored. We demonstrate here that administration of lacto-N-fucopentaose III (LNFPIII), a LewisX-containing immunomodulatory glycan found in human milk and on parasitic helminths, improves glucose tolerance and insulin sensitivity in diet-induced obese mice. This effect is mediated partly through increased interleukin-10 (Il-10) production by LNFPIII-activated macrophages and dendritic cells, which reduces white adipose tissue inflammation and sensitizes the insulin response of adipocytes. Concurrently, LNFPIII treatment upregulates nuclear receptor subfamily 1, group H, member 4 (Fxr-α, also known as Nr1h4) to suppress lipogenesis in the liver, conferring protection against hepatosteatosis. At the signaling level, the extracellular signal-regulated kinase (Erk)-activator protein 1 (Ap1) pathway seems to mediate the effects of LNFPIII on both inflammatory and metabolic pathways. Our results suggest that LNFPIII may provide new therapeutic approaches to treat metabolic diseases.

原文地址

http://www.nature.com/nm/journal/v18/n11/abs/nm.2962.html

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本文链接: http://www.bioku.cn/201301/nature-medicine-lnfpiii-hepatosteatosis-insulin-resistance-metabolic/
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