Mechanisms underlying reduced weight gain in intestinal fatty acid-binding protein (IFABP) null mice

Intestinal-fatty acid binding protein (IFABP; FABP2) is a 15-kDa intracellular protein abundantly present in the cytosol of the small intestinal (SI) enterocyte. High-fat (HF) feeding of IFABP^-/- mice resulted in reduced weight gain and fat mass relative to wild-type (WT) mice. Here, we examined intestinal properties that may underlie the observed lean phenotype of high fat-fed IFABP^-/- mice. No alterations in fecal lipid content were found, suggesting that the IFABP^-/- mice are not malabsorbing dietary fat. However, the total excreted fecal mass, normalized to food intake, was increased for the IFABP^-/- mice relative to WT mice. Moreover, intestinal transit time was more rapid in the IFABP^-/- mice. IFABP^-/- mice displayed a shortened average villus length, a thinner muscularis layer, reduced goblet cell density, and reduced Paneth cell abundance. The number of proliferating cells in the crypts of IFABP^-/- mice did not differ from that of WT mice, suggesting that the blunt villi phenotype is not due to alterations in proliferation. IFABP^-/- mice were observed to have altered expression of genes and proteins related to intestinal structure, while immunohistochemical analyses revealed increased staining for markers of inflammation. Taken together, these studies indicate that the ablation of IFABP, coupled with high-fat feeding, leads to changes in gut motility and morphology, which likely contribute to the relatively leaner phenotype occurring at the whole-body level. Thus, IFABP is likely involved in dietary lipid sensing and signaling, influencing intestinal motility, intestinal structure, and nutrient absorption, thereby impacting systemic energy metabolism.NEW & NOTEWORTHY Intestinal fatty acid binding protein (IFABP) is thought to be essential for the efficient uptake and trafficking of dietary fatty acids. In this study, we demonstrate that high-fat-fed IFABP^-/- mice have an increased fecal output and are likely malabsorbing other nutrients in addition to lipid. Furthermore, we observe that the ablation of IFABP leads to marked alterations in intestinal morphology and secretory cell abundance.