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Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

ABSTRACT: Dietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and 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 mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid-laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced foam cell formation, inflammatory gene expression, and chyle-induced activation of ER stress. Induction of macrophage Angptl4 by fatty acids is part of a mechanism that serves to reduce postprandial lipid uptake from chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled saturated fat-induced inflammation.

SUBMITTER: Lichtenstein L

PROVIDER: S-EPMC3387545 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

Lichtenstein Laeticia L Mattijssen Frits F de Wit Nicole J NJ Georgiadi Anastasia A Hooiveld Guido J GJ van der Meer Roelof R He Yin Y Qi Ling L Köster Anja A Tamsma Jouke T JT Tan Nguan Soon NS Müller Michael M Kersten Sander S

Cell metabolism 20101201 6

Dietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and 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 m ...[more]

PMID: 21109191

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Project description:BackgroundThe diagnosis of proximal small bowel involvement in Crohn's disease (CD) can be challenging at magnetic resonance enterography (MRE). The inflammatory process in CD can be associated with peri-intestinal inflammatory reactions, including the presence of inflamed mesenteric lymph nodes.ObjectivesTo evaluate the significance of inflamed mesenteric lymph nodes adjacent to the jejunum at MRE in CD and the association with proximal bowel disease as detected by video capsule endoscopy (VCE).DesignThis retrospective study was performed in two tertiary medical centres, and included 64 patients with CD who underwent MRE as well as VCE within 1 year.MethodsData were collected for examinations performed between August 2013 and February 2021. MRE images were independently reviewed by radiologists who were blinded to the clinical data. Association between the presence of mesenteric lymph nodes adjacent to jejunum at MRE and disease activity according to VCE Lewis scores of proximal small bowel was examined.ResultsVCE detected proximal disease in 24/64 patients (37.5%). Presence of regional lymph nodes in the jejunal mesentery was significantly associated with jejunal disease as seen on VCE (p < 0.001). Of the 20 patients who had proximal mesenteric lymph nodes at MRE, 15 (75%) had jejunal disease at VCE (sensitivity, 62.5%; specificity, 87.5%; and negative and positive predictive values, 79.5 and 75%, respectively). The number of regional lymph nodes was positively correlated with jejunal disease (mean: 2.63 ± 2.90 versus 0.78 ± 2.60, p = 0.01). Other MRE features of lymph nodes were not significantly predictive of jejunal CD.ConclusionIn patients with CD, inflamed regional lymph nodes in the jejunal mesentery at MRE can be valuable to suggest proximal small bowel disease, even when bowel wall features at imaging do not suggest disease involvement.Plain language summaryThe diagnosis of proximal small bowel involvement in Crohn's disease (CD) can be challenging at magnetic resonance enterography (MRE). We analysed MRE examinations in patients with CD for the presence of lymph nodes adjacent to the proximal small bowel. We included 64 patients with CD who had MRE examinations and video capsule endoscopy (VCE) examinations within 1 year. Of 64 patients, 24 had proximal small bowel disease according to VCE. We found that of 20 patients who had regional mesenteric lymph nodes in the jejunal mesentery at MRE, 15 had proximal bowel disease involvement. We also found that patients with jejunal disease had a larger number of regional lymph nodes compared to patients without jejunal disease. All but one patient had normal appearing bowel at MRE. But, using regional mesenteric lymphadenopathy at MRE as an indicator for disease, 15/24 (62.5%) patients with proximal small bowel disease were detected. We therefore conclude that regional mesenteric lymph nodes assessment at MRE can aid diagnose proximal bowel disease, even when the proximal bowel looks normal at imaging. Presence of proximal mesenteric lymph nodes at MRE in patients with CD possibly warrant further investigation of the proximal small bowel by endoscopic measures.

Dataset Information

Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

Publications

Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

Similar Datasets

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