Retinol metabolism signaling participates in microbiota-regulated fat deposition in obese mice

Obesity is a global pandemic threatening public health, excess fat accumulation and overweight are its characteristics. In this study, the interplay between gut microbiota and retinol metabolism in modulating fat accumulation was verified. We observed gut microbiota depletion reduced the body weight (P<0.05) and the ratios of white adipose tissues (WATs) to body weight (P<0.05) in high-fat diet (HFD) fed-mice. Both the hepatic metabolomics and transcriptomics analyses confirmed that gut microbiota modulated fat accumulation in obese mice. Besides, the kyoto encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network of RNA-seq results indicated that retinol metabolism signaling may be involved in the microbiota-regulated fat deposition. Furthermore, activated retinol metabolism signaling by all-trans retinoic acid (atRA) supplementation reduced body weight (P<0.05) and WAT accumulation in obese mice. On the other hand, 16S rRNA gene sequencing of the ileal microbiota suggested that atRA supplementation, in turn, increased the microbial diversity and induced the growth of beneficial bacteria including Parabacteroides, Bacteroides, Clostridium_XVIII, Bifidobacterium, Enterococcus, Bacillus, Leuconostoc, and Lactobacillus in obese mice. Spearman correlation showed that atRA decreased the bacteria (Parvibacter, Asaccharobacter, Romboutsia, and Clostridium_IV) that were positively associated with body and WAT weights, whereas increased the bacteria (Lactobacillus) that were negatively associated with body and WAT weights. Together, this study reveals the interaction between the gut microbiota and retinol metabolism signaling in regulating adipose accumulation and obesity. It is expected of this finding to provide new insights to prevent and develop therapeutic measures of obesity-related metabolic syndrome.