Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling

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. [Display omitted] •The gut microbiota contributes to phenotypic differences in mice fed lard or fish oil•Mice lacking MyD88 or TRIF are protected against WAT inflammation•Microbial-derived factors induce CCL2 in adipocytes through TLR4, MyD88, and TRIF•Microbial-induced CCL2 enhances macrophage accumulation in WAT Caesar et al. reveal how saturated lipids in lard affect gut microbial composition to promote obesity and WAT inflammation via TLR signaling and CCL2; in contrast, mice fed a fish-oil diet enriched in polyunsaturated fatty acids are protected. Transfer of microbiota from fish-oil-fed mice dampens lard-induced inflammation.