Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways.
Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways.
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作者：
寄生蠕虫表达宿主样聚糖以减弱人类宿主的免疫应答。这种免疫调节机制在控制与慢性炎症相关的代谢功能障碍方面的治疗潜力尚未探索。我们在这里证明，乳糖-N-岩藻五糖III（LNFPIII），一种在人乳和寄生虫中发现的含有LewisX的免疫调节聚糖，可以改善饮食诱导的肥胖小鼠的葡萄糖耐量和胰岛素敏感性。这种作用部分通过LNFP III激活的巨噬细胞和树突细胞增加的IL-10产生介导，其减少了白色脂肪组织炎症并使脂肪细胞的胰岛素反应敏感。同时，LNFP III治疗上调核受体Fxr-α（或Nr 1h 4）以抑制肝脏中的脂肪生成，从而提供针对脂肪肝的保护。在信号水平，细胞外信号调节激酶（Erk）-Ap 1途径似乎介导LNFP III对炎症和代谢途径的影响。我们的研究结果表明，LNFPIII可能提供新的治疗方法来治疗代谢性疾病。
Parasitic worms express host-like glycans to attenuate the immune response of human hosts. The therapeutic potential of this immunomodulatory mechanism in controlling metabolic dysfunction 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 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 up-regulates nuclear receptor Fxr-α (or Nr1h4) to suppress lipogenesis in the liver, conferring protection against hepatosteatosis. At the signaling level, the extracellular signal-regulated kinase (Erk)-Ap1 pathway appears to mediate the effects of LNFPIII on both inflammatory and metabolic pathways. Our results suggest that LNFPIII may provide novel therapeutic approaches to treat metabolic diseases.
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影响因子：
64.5
作者：
Cao H;Gerhold K;Mayers JR;Wiest MM;Watkins SM;Hotamisligil GS
通讯作者：
Hotamisligil GS
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
7.7
作者：
Hong EG;Ko HJ;Cho YR;Kim HJ;Ma Z;Yu TY;Friedline RH;Kurt-Jones E;Finberg R;Fischer MA;Granger EL;Norbury CC;Hauschka SD;Philbrick WM;Lee CG;Elias JA;Kim JK
通讯作者：
Kim JK
DOI：
10.1590/s0100-879x2004000500006
发表时间：
2004-05-01
影响因子：
2.3
作者：
Foss-Freitas, M.C.;Foss, M.C.
通讯作者：
Foss, M.C.
影响因子：
2.7
作者：
Chang, Yih-Hsin;Huang, Chien-Ning;Shiau, Ming-Yuh
通讯作者：
Shiau, Ming-Yuh