Gut Microbiota and Phenotypic Changes Induced by Ablation of Liver- and Intestinal-Type Fatty Acid-Binding Proteins

Abstract

Intestinal fatty acid-binding protein (IFABP; FABP2) and liver fatty acid-binding protein (LFABP; FABP1) are small intracellular lipid-binding proteins. Deficiency of either of these proteins in mice leads to differential changes in intestinal lipid transport and metabolism, and to markedly divergent changes in whole-body energy homeostasis. The gut microbiota has been reported to play a pivotal role in metabolic process in the host and can be affected by host genetic factors. Here, we examined the phenotypes of wild-type (WT), LFABP−/−, and IFABP−/− mice before and after high-fat diet (HFD) feeding and applied 16S rRNA gene V4 sequencing to explore guild-level changes in the gut microbiota and their associations with the phenotypes. The results show that, compared with WT and IFABP−/− mice, LFABP−/− mice gained more weight, had longer intestinal transit time, less fecal output, and more guilds containing bacteria associated with obesity, such as members in family Desulfovibrionaceae. By contrast, IFABP−/− mice gained the least weight, had the shortest intestinal transit time, the most fecal output, and the highest abundance of potentially beneficial guilds such as those including members from Akkermansia, Lactobacillus, and Bifidobacterium. Twelve out of the eighteen genotype-related bacterial guilds were associated with body weight. Interestingly, compared with WT mice, the levels of short-chain fatty acids in feces were significantly higher in LFABP−/− and IFABP−/− mice under both diets. Collectively, these studies show that the ablation of LFABP or IFABP induced marked changes in the gut microbiota, and these were associated with HFD-induced phenotypic changes in these mice.

The Multifunctional Family of Mammalian Fatty Acid–Binding Proteins

“…This suggests that FABP2 null mice are malabsorbing nutrients in general, which likely contributes to their leaner phenotype ( 96 ). In line with this, gut microbiota of FABP2 −/− mice showed an increase in antiobesity-promoting guilds after HFD feeding relative to WT mice ( 182 ). The ablation of FABP2 induces differential alterations in male and female mice.…”

“…Within the intestine itself, mucosal lipid metabolism was differentially modified, with significant decreases in FA incorporation into triacylglycerol (TG) relative to phospholipid (PL) in FABP2 −/− mice, whereas FABP1 −/− mice displayed reduced monoacylglycerol incorporation in TG relative to PL, as well as reduced FA oxidation, possibly indicating participation of FABP1 in FA trafficking to oxidative pathways and explaining, at least in part, the obese phenotype. FABP1 −/− mice on an HFD had longer intestinal transit time, less fecal output, and more guilds containing bacteria associated with obesity ( 182 ). Higher mucosal levels of the orexigenic endocannabinoids arachidonoylethanolamine (AEA) and 2-arachidonoylglyccerol (2-AG) were also observed in FABP1 KO mice, a finding that may be related to the increased appetite in these mice ( 49 ).…”

Tannic Acid Extracted from Galla chinensis Supplementation in the Diet Improves Intestinal Development through Suppressing Inflammatory Responses via Blockage of NF-κB in Broiler Chickens

“…Intestinal FABP1 is a small intracellular lipid-binding protein. Previous study in mice showed that deficiency of FABP1 lead to divergent changes in intestinal lipid transport and metabolism and whole-body energy homeostasis [ 23 ]. Wang et al [ 16 ] demonstrated that TA from Galla chinensis supplementation increased the expressions of nutrient transporters SLC6A19 and SLC15A1 in small intestine of weaned piglets.…”

Integrated meta-omics reveals the regulatory landscape involved in lipid metabolism between pig breeds

“…3 B). The transporters of intestinal FABPs are intracellular lipid-binding proteins and display high affinity binding for long-chain fatty acids [ 54 ], and FABP1 preferentially directs fatty acid toward oxidative pathways while FABP2 directs fatty acids to triacylglycerol (TAG) synthesis [ 55 ]. In addition, small intestine-rich SLC27A4 (fatty acid transport protein 4, FATP4) is a cell-surface fatty acid transport protein for the trafficking of long-chain fatty acids [ 56 ] and exhibits acyl-CoA synthetase activity for lipid beta-oxidation [ 57 ].…”