EVIDENCE FOR A ROLE OF THE GUT HORMONE PYY IN THE REGULATION OF INTESTINAL FATTY-ACID-BINDING PROTEIN TRANSCRIPTS IN DIFFERENTIATED SUBPOPULATIONS OF INTESTINAL EPITHELIAL-CELL HYBRIDS

Peptide tyrosine tyrosine (PYY) is a gut hormone present in endocrine cells in the lower intestine that can be released by the presence of l uminal free fatty acids (FFAs). The biological action of this peptide includes inhibition of gut motility and gastrointestinal and pancreati c secretions. Intestinal fatty acid-binding protein (I-FABP) binds FFA and may be involved in their cytosolic trafficking. Quantitative in s itu hybridization on heterogeneous populations of small intestinal som atic cell hybrids selected for endogenous I-FABP expression (hBRIE 380 i cells) demonstrated a 5-fold increase in I-FABP transcripts in respo nse to PYY (within 6 h) that was confined to clusters of differentiate d cells, whereas ribonuclease protection assays performed on heterogen eous populations of these cells showed no significant differences. Hig h affinity PW receptors, with an IC50 of 5-50 pw, were identified in b oth differentiated and nondifferentiated cell populations, as determin ed by competitive binding assays and autoradiography. In situ hybridiz ation of rat ileal tissue also revealed differing patterns of mRNA exp ression for liver fatty acid-binding protein (L-FABP) and I-FABP. Only I-FABP mRNA was detected in the villus tips. This localization correl ated with the expression pattern of I-FABP mRNA in the hBRIE 380i cell s where changes in transcripts were observed only in differentiated ce lls that did not incorporate bromodeoxyuridine. The sustained expressi on of I-FABP transcripts in the villar tips suggests (unlike L-FABP) t hat older terminally differentiated cell populations of the mucosa can still be PW responsive. These studies demonstrate that physiological concentrations of PW can regulate I-FABP and place this peptide in a k ey position as part of a feedback system that determines the processin g of cytosolic FFA in the enterocyte. In addition, these studies sugge st a mechanism whereby luminal agents can modulate expression of prote ins in terminally differentiated cells in the gastrointestinal mucosa.