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

TLDR

Dietary lipids can modulate circulating inflammatory microbial factors, so white adipose tissue inflammation driven by dietary lipids may depend partly on gut‑microbiota interactions. Mice fed lard for 11 weeks showed increased TLR activation, WAT inflammation, and insulin resistance versus fish‑oil‑fed controls, effects largely attributable to microbiota composition—as shown by protection in Trif‑/‑, Myd88‑/‑, and germ‑free mice and the role of CCL2—demonstrating that gut microbiota amplify saturated‑lipid‑induced metabolic 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.