Differing Functions of Liver and Intestinal‐Fatty Acid Binding Proteins: Examination of the LFABP/IFABP Double Knockout Mouse.

Abstract

The intestinal enterocyte expresses two fatty acid‐binding proteins (FABP): intestinal‐ (IFABP; FABP2) and liver‐FABP (LFABP; FABP1). These proteins have similar tertiary structures, but display different mechanisms of long‐chain fatty acid (LCFA) transport, and some differences in ligand binding specificities. The individual functions of IFABP and LFABP in intestinal lipid absorption and metabolism are incompletely understood. We previously reported that ablation of these proteins in mice results in divergent phenotypes in response to high‐fat feeding; LFABP‐/‐ mice gain more weight and fat mass than WT mice, while IFABP‐/‐ mice are lean. In the present studies, we generated LFABP and IFABP double knockout mice (DKO) to study the effects of simultaneous ablation of these proteins. Male C57BL/6 (WT), IFABP‐/‐, LFABP‐/‐ and DKO mice were fed 10 or 45 kcal% fat diets containing LCFA for 12 weeks. Interestingly, the phenotype of the DKO mice was integrated between those of the LFABP‐/‐ and IFABP‐/‐ mice, with body weight and fat mass that were between those found for the single knockouts. Remarkably, DKO mice display no evidence of lipid malabsorption, indicating that these proteins are not required for bulk uptake of FA into the intestine. Overall, simultaneous ablation of LFABP and IFABP does not reveal a dominant effect of either protein, but rather an additive effect of ablation of each of the proteins. The results suggest that IFABP and LFABP have different functions in intestinal lipid homeostasis, resulting in differential downstream alterations in systemic energy metabolism.