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

Cell Metab. 2015 Oct 6;22(4):658-68. doi: 10.1016/j.cmet.2015.07.026. Epub 2015 Aug 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / deficiency
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adipose Tissue, White / metabolism*
  • Animals
  • Bacteria / classification
  • Bacteria / genetics
  • Body Weight / drug effects
  • Chemokine CCL2 / metabolism
  • DNA, Bacterial / analysis
  • Diet, High-Fat*
  • Fish Oils / pharmacology
  • Gastrointestinal Microbiome*
  • Gastrointestinal Tract / microbiology
  • Inflammation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Phylogeny
  • Signal Transduction
  • Toll-Like Receptors / metabolism*

Substances

  • Adaptor Proteins, Vesicular Transport
  • Chemokine CCL2
  • DNA, Bacterial
  • Fish Oils
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • TICAM-1 protein, mouse
  • Toll-Like Receptors

Associated data

  • GEO/GSE70922