Abstract
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 fatty acids (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, whereas LFABP(-/-) mice had reduced monoacylglycerol 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, whereas 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 and arachidonoylethanolamine 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.
Highlights
Intestinal and liver fatty acid-binding proteins (IFABP and liver FABP (LFABP)) are coexpressed in the enterocyte, but their individual functions are not known
Ablation of LFABP or intestinal FABP (IFABP) Differentially Affects Body Weight, Body Composition, and Food Intake—The BW and body fat mass (FM) of IFABPϪ/Ϫ and LFABPϪ/Ϫ mice were similar to WT prior to the start of feeding, but the percentage of fat-free mass (FFM) of LFABPϪ/Ϫ mice was slightly lower than WT (p Ͻ 0.05)
After 12 weeks of high fat feeding, different BW phenotypes were readily evident between the IFABPϪ/Ϫ and LFABPϪ/Ϫ mice
Summary
Intestinal and liver fatty acid-binding proteins (IFABP and LFABP) are coexpressed in the enterocyte, but their individual functions are not known. 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. Changes in body weight and fat may arise, in part, from altered food intake; mucosal levels of the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamine 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
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