Altered Small Intestinal Morphology and Whole‐Body Energy Homeostasis in the Intestinal Fatty Acid Binding Protein (IFABP) Knockout Mouse

Abstract

Intestinal‐fatty acid binding protein (IFABP; FABP2) is a 15 kDa intracellular protein present in high abundance in the cytosol of the small intestinal (SI) enterocyte. High fat (HF) feeding of IFABP−/− mice resulted in lower weight gain and reduced fat mass relative to WT mice, revealing that ablation of this intestine‐specific protein leads to dramatic whole‐body phenotypic alterations (Gajda et al., JBC 2013 288:30330–30344). To understand the mechanisms leading to these differences in systemic energy homeostasis, we examined intestinal properties that may underlie the observed lean phenotype. Fecal lipid analysis demonstrated that IFABP−/− mice did not differ in their fecal lipid content, suggesting they are not malabsorbing dietary fat. However, the total excreted fecal mass for the IFABP−/− mice was significantly increased relative to WT mice. Moreover we found reduced intestinal transit time in the IFABP−/− mice, which underlies the increased fecal excretion. During tissue collection it was noted that the small intestine of IFABP−/− mice appeared to be more fragile, thus we questioned whether they may have alterations in intestinal structure. Histological analysis demonstrated that IFABP−/− mice have a shortened average villus length, reduced goblet cell density, and a reduced Paneth cell abundance relative to WT mice. BrdU proliferation assays demonstrated that the amount of proliferating cells in the crypts of IFABP−/− mice does not differ from that of WT mice, suggesting that the blunt villi phenotype is likely not due to alterations in proliferation. IHC analyses revealed increased staining for markers of inflammation, which is often observed in animals that have increased intestinal permeability. Taken together, while the effects of IFABP ablation within the enterocyte may be relatively modest in terms of lipid, there are clear changes in gut motility and morphology which likely contribute to the dramatically different phenotypes occurring at the whole‐body level. Thus, these results suggest that IFABP is likely involved in dietary lipid sensing and signaling, influencing intestinal motility, nutrient absorption, and intestinal structure, thereby impacting systemic energy metabolism.Support or Funding InformationThis work was supported by National Institutes of Health Grant DK‐38389 and NJAES (to J. S.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.