title: Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling.
abstract: Dietary lipids may influence the abundance of circulating inflammatory microbial factors. Hence, inflammation in white adipose tissue (WAT) induced by dietary lipids may be partly dependent on their interaction with the gut microbiota. Here, we show that mice fed lard for 11 weeks have increased Toll-like receptor (TLR) activation and WAT inflammation and reduced insulin sensitivity compared with mice fed fish oil and that phenotypic differences between the dietary groups can be partly attributed to differences in microbiota composition. Trif(-/-) and Myd88(-/-) mice are protected against lard-induced WAT inflammation and impaired insulin sensitivity. Experiments in germ-free mice show that an interaction between gut microbiota and saturated lipids promotes WAT inflammation independent of adiposity. Finally, we demonstrate that the chemokine CCL2 contributes to microbiota-induced WAT inflammation in lard-fed mice. These results indicate that gut microbiota exacerbates metabolic inflammation through TLR signaling upon challenge with a diet rich in saturated lipids.
authors: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden. Electronic address: robert.caesar@wlab.gu.se.
authors: Robert
authors: R
authors: Caesar
authors: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
authors: Valentina
authors: V
authors: Tremaroli
authors: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
authors: Petia
authors: P
authors: Kovatcheva-Datchary
authors: Université Catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, WELBIO (Walloon Excellence in Life Sciences and BIOtechnology), 1200 Brussels, Belgium.
authors: Patrice D
authors: PD
authors: Cani
authors: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: fredrik.backhed@wlab.gu.se.
authors: Fredrik
authors: F
authors: Bäckhed
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D004269:DNA, Bacterial / Q000032:analysis; D059305:Diet, High-Fat; D005395:Fish Oils / Q000494:pharmacology; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D010802:Phylogeny; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018932:Chemokine CCL2; D004269:DNA, Bacterial; D005395:Fish Oils; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse