Different functions of intestinal and liver-type fatty acid-binding proteins in intestine and in whole body energy homeostasis

Abstract

It has long been known that mammalian enterocytes coexpress two members of the fatty acid-binding protein (FABP) family, the intestinal FABP (IFABP) and the liver FABP (LFABP). Both bind long-chain fatty acids and have similar though not identical distributions in the intestinal tract. While a number of in vitro properties suggest the potential for different functions, the underlying reasons for expression of both proteins in the same cells are not known. Utilizing mice genetically lacking either IFABP or LFABP, we directly demonstrate that each of the enterocyte FABPs participates in specific pathways of intestinal lipid metabolism. In particular, LFABP appears to target fatty acids toward oxidative pathways and dietary monoacylglycerols toward anabolic pathways, while IFABP targets dietary fatty acids toward triacylglycerol synthesis. The two FABP-null models also displayed differences in whole body response to fasting, with LFABP-null animals losing less fat-free mass and IFABP-null animals losing more fat mass relative to wild-type mice. The metabolic changes observed in both null models appear to occur by nontranscriptional mechanisms, supporting the hypothesis that the enterocyte FABPs are specifically trafficking their ligands to their respective metabolic fates.

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei

“…In vertebrates, the absorption and transport of short-to medium-chain FAs occurs differently in enterocytes, as LCFAs are usually reesterifi ed inside the cell. There is evidence indicating that both FABP1 and FABP2 participate in the cellular uptake and transport of unesterifi ed FAs and the lipid metabolism ( 16,80,81 ). However, some authors report that they play a role in lipid sensing but not in direct dietary FA absorption ( 13,62,82,83 ).…”

Decreased body weight and hepatic steatosis with altered fatty acid ethanolamide metabolism in aged L-Fabp mice

“…Our studies have demonstrated that female mice with germline deletion of L-Fabp are protected against weight gain and hepatic steatosis when fed high saturated fat (SF) diets (15)(16)(17). This phenotype cannot be attributed to increased energy metabolism or decreased absorption of dietary fat, although the kinetics of intestinal fatty acid (FA) uptake is altered in L-Fabp Ϫ / Ϫ mice ( 17,18 ). In general, L-Fabp Ϫ / Ϫ mice fed a high-fat diet exhibit a subtle (although not statistically signifi cant) decrease in average daily food consumption, a difference which would over time be suffi cient to reduce weight gain ( 15 ).…”

Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice

“…L-FABP, and oxidation such as PPAR␣ and PPAR␥. Furthermore, L-FABP can target fatty acids to oxidative degradation (40). Therefore, higher ␤-oxidation of FFA might be secondary to high FFA concentrations.…”