Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.
Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.
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DOI：
10.1016/j.cmet.2010.11.002
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发表时间：
2010-12-01
期刊：
影响因子：
29
通讯作者：
Kersten S
中科院分区：
文献类型：
--
作者：
Lichtenstein L;Mattijssen F;de Wit NJ;Georgiadi A;Hooiveld GJ;van der Meer R;He Y;Qi L;Köster A;Tamsma JT;Tan NS;Müller M;Kersten S
膳食饱和脂肪与许多慢性疾病有关，包括心血管疾病。在这里，我们展示了脂蛋白脂肪酶抑制剂ANGPTL4对饮食饱和脂肪显著的促炎作用的保护作用。值得注意的是，在缺乏ANGPTL4的小鼠中，饮食饱和脂肪诱导了一种严重的、最终致命的表型，其特征是纤维蛋白脓性腹膜炎、腹水、肠纤维化和恶病质。在这些异常之前，由起源于肠系膜淋巴结(MLN)的饱和但不饱和脂肪或中链脂肪引起的大量急性时相反应。MLN急剧扩张，含有大量富含脂质的巨噬细胞。在与乳糜液孵育的腹膜巨噬细胞中，ANGPTL4显著减少巨噬细胞泡沫细胞的形成、炎症基因的表达以及乳糜液诱导的内质网应激途径的激活。这些数据揭示了一种新的机制，即脂肪酸诱导巨噬细胞ANGPTL4通过抑制甘油三酯水解来减少餐后脂肪乳糜脂进入驻留巨噬细胞的脂肪摄取，从而防止巨噬细胞激活和泡沫细胞形成，并防止进行性的、不受控制的饮食饱和脂肪诱导的炎症。
Dietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we show that the lipoprotein lipase inhibitor Angptl4 protects against the pronounced pro-inflammatory effects of dietary saturated fat. Strikingly, in mice lacking Angptl4, dietary saturated fat induces a severe and ultimately lethal phenotype characterized by fibrinopurulent peritonitis, ascites, intestinal fibrosis, and cachexia. These abnormalities are preceded by a massive acute phase response induced by saturated but not unsaturated fat or medium-chain fat, originating in the mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced macrophage foam cell formation, inflammatory gene expression, and chyle-induced activation of the ER stress pathway. The data reveal a novel mechanism in which induction of macrophage Angptl4 by fatty acids serves to reduce postprandial lipid uptake from fatty chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled dietary saturated fat-induced inflammation.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
82.9
作者：
Erbay, Ebru;Babaev, Vladimir R.;Mayers, Jared R.;Makowski, Liza;Charles, Khanichi N.;Snitow, Melinda E.;Fazio, Sergio;Wiest, Michelle M.;Watkins, Steven M.;Linton, MacRae F.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
影响因子：
11.8
作者：
Gale, NW;Thurston, G;Yancopoulos, GD
通讯作者：
Yancopoulos, GD
影响因子：
4
作者：
Diakogiannaki, Eleftheria;Welters, Hannah J.;Morgan, Noel G.
通讯作者：
Morgan, Noel G.