White adipose tissue (WAT) inflammation and metabolic diseases are associated with diets rich in saturated fatty acids, and host dietary composition affects the gut microbiota. Caesar et al. investigated whether WAT inflammation was mediated by the gut microbiota in response to the type of lipids in the diet. Mice were fed isocaloric diets that were based either on lard (a source of saturated lipids) or fish oil (a source of polyunsaturated lipids). After 11 weeks, the lard-fed mice gained more weight and had higher fasting insulin and glucose concentrations than mice fed a fish oil–based diet. Cell lines expressing Toll-like receptor 2 (TLR2) or TLR4, which respond to microbial products, showed increased activation when exposed to serum from lard-fed mice compared with serum from fish oil–fed mice. Lard-fed mice lacking the TLR adaptor protein MyD88 (MyD88–/– mice) gained less weight and had smaller adipocytes compared with lard-fed wild-type mice. Immune cell infiltration of the WAT was reduced in lard-fed MyD88–/– mice or those lacking the TLR adaptor protein TRIF (Trif–/– mice) compared with lard-fed wild-type mice. Principal component analysis (PCA) of data from 454 pyrosequencing of the 16S rRNA gene (which are a component of prokaryote ribosomes and can be used to reconstruct phylogenies) in cecal contents revealed that the phylogenetic diversity of the gut microbiota of the lard-fed mice was decreased compared with that of the fish oil–fed mice. In addition, conventionally raised mice gained more weight than germ-free mice, whether on the lard or fish oil diet. Antibiotic-treated mice that received transplanted microbiota from fish oil–fed mice gained less weight when subsequently fed a lard-based diet compared with mice that received microbiota from lard-fed mice. In the WAT of lard-fed mice, the expression of Ccl2 (which encodes a chemokine that attracts macrophages) was greater in mice that were conventionally raised than in germ-free mice and in wild-type mice than in MyD88–/– or Trif–/– mice. Adipocytes and macrophages exposed to serum from lard-fed, conventionally raised mice showed increased expression of the gene encoding the inflammatory cytokine tumor necrosis factor–α, suggesting that factors in the blood of lard-fed mice stimulated an inflammatory response. Last, germ-free mice that were conventionalized and treated with a CCL2 inhibitor had decreased infiltration of immune cells in WAT compared with WAT from control mice. Thus, this study suggests that an interaction between gut microbiota and lipids in the diet increases WAT inflammation.
R. Caesar, V. Tremaroli, P. Kovatcheva-Datchary, P. D. Cani, F. Bäckhed, Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 22, 658–668 (2015). [PubMed]