The enterocyte expresses two fatty acid-binding proteins (FABP), intestinal-FABP (IFABP; FABP2) and liver-FABP (LFABP; FABP1). LFABP is also expressed in liver. Despite ligand transport and binding differences, it has remained uncertain whether these intestinally-coexpressed proteins, which both bind long chain FA, are functionally distinct. Here we directly compared IFABP-/- and LFABP-/- mice fed high-fat diets containing long-chain saturated or unsaturated fatty acids, reasoning that providing an abundance of dietary lipid would reveal unique functional properties. The results showed that mucosal lipid metabolism was indeed differentially modified, with significant decreases in FA incorporation into triacylglycerol (TG) relative to phospholipid (PL) in IFABP-/- mice, while LFABP-/- mice had reduced monoacylglycerol (MG) incorporation in TG relative to PL, and reduced radiolabeled monoacylglycerol (MG) incorporation in TG relative to PL, as well as reduced FA oxidation. Interestingly, striking differences were found in whole body energy homeostasis: LFABP-/- mice fed high-fat diets became obese relative to WT, while IFABP-/- mice displayed an opposite, lean, phenotype. Fuel utilization followed adiposity, with LFABP-/- mice preferentially utilizing lipids, and IFABP-/- mice preferentially metabolizing carbohydrate for energy production. Changes in body weight and fat may arise, in part, from altered food intake; mucosal levels of the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamine (AEA) were elevated in LFABP-/-, perhaps contributing to increased energy intake. This direct comparison provides evidence that LFABP and IFABP have distinct roles in intestinal lipid metabolism; differential intracellular functions in intestine and in liver, for LFABP-/- mice, result in divergent downstream effects at the systemic level.

PMID:

 23990461
[PubMed – as supplied by publisher]