The proximal intestinal Fatty Acid-Binding Proteins liver FABP (LFABP) and intestinal FABP (IFABP) differentially modulate whole body energy homeostasis but are not centrally involved in net dietary lipid absorption: Studies of the LFABP/IFABP double knockout mouse

Angela M. Gajda, Hiba R. Tawfeeq, Atreju I. Lackey, Yin Xiu Zhou, Hamzeh Kanaan, Arete Pappas, Heli Xu, Sarala Kodukula, Judith Storch

Research output: Contribution to journalArticlepeer-review

Abstract

Proximal intestinal enterocytes expresses both intestinal-fatty acid binding protein (IFABP; FABP2) and liver-FABP (LFABP; FABP1). These FABPs are thought to be important in the net uptake of dietary lipid from the intestinal lumen, however their specific and potentially unique functions in the enterocyte remain incompletely understood. We previously showed markedly divergent phenotypes in LFABP−/− vs. IFABP−/− mice fed high-fat diets, with the former becoming obese and the latter remaining lean relative to wild-type (WT) mice, supporting different functional roles for each protein. Interestingly, neither mouse model displayed increased fecal lipid concentration, raising the question of whether the presence of one FABP was sufficient to compensate for absence of the other. Here, we generated an LFABP and IFABP double knockout mouse (DKO) to determine whether simultaneous ablation would lead to fat malabsorption, and to further interrogate the individual vs. overlapping functions of these proteins. Male WT, IFABP−/−, LFABP−/−, and DKO mice were fed a low-fat (10 % kcal) or high-fat (45 % kcal) diet for 12 weeks. The body weights and fat mass of the DKO mice integrated those of the LFABP−/− and IFABP−/− single knockouts, supporting the notion that IFABP and LFABP have distinct functions in intestinal lipid assimilation that result in downstream alterations in systemic energy metabolism. Remarkably, no differences in fecal fat concentrations were found in the DKO compared to WT, revealing that the FABPs are not required for net intestinal uptake of dietary lipid.

Original languageEnglish (US)
Article number159238
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1868
Issue number1
DOIs
StatePublished - Jan 2023

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • Fatty acid
  • Fatty acid binding protein
  • Intestinal metabolism
  • Lipid
  • Lipid absorption
  • Monoacyglycerol

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