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 luminal free fatty acids (FFAs). The biological action of this peptide includes inhibition of gut motility and gastrointestinal and pancreatic secretions. Intestinal fatty acid-binding protein (I-FABP) binds FFA and may be involved in their cytosolic trafficking. Quantitative in situ hybridization on heterogeneous populations of small intestinal somatic cell hybrids selected for endogenous I-FABP expression (hBRIE 380i cells) demonstrated a 5-fold increase in I-FABP transcripts in response to PYY (within 6 h) that was confined to clusters of differentiated cells, whereas ribonuclease protection assays performed on heterogeneous populations of these cells showed no significant differences. High affinity PYY receptors, with an IC50 of 5–50 pm, were identified in both differentiated and nondifferentiated cell populations, as determined by competitive binding assays and autoradiography. In situ hybridization of rat ileal tissue also revealed differing patterns of mRNA expression for liver fatty acid-binding protein (L-FABP) and I-FABP. Only I-FABP mRNA was detected in the villus tips. This localization correlated with the expression pattern of I-FABP mRNA in the hBRIE 380i cells where changes in transcripts were observed only in differentiated cells that did not incorporate bromodeoxyuridine. The sustained expression of I-FABP transcripts in the villar tips suggests (unlike L-FABP) that older terminally differentiated cell populations of the mucosa can still be PYY responsive. These studies demonstrate that physiological concentrations of PYY can regulate I-FABP and place this peptide in a key position as part of a feedback system that determines the processing of cytosolic FFA in the enterocyte. In addition, these studies suggest a mechanism whereby luminal agents can modulate expression of proteins in terminally differentiated cells in the gastrointestinal mucosa. Peptide tyrosine tyrosine (PYY) is a gut hormone present in endocrine cells in the lower intestine that can be released by the presence of luminal free fatty acids (FFAs). The biological action of this peptide includes inhibition of gut motility and gastrointestinal and pancreatic secretions. Intestinal fatty acid-binding protein (I-FABP) binds FFA and may be involved in their cytosolic trafficking. Quantitative in situ hybridization on heterogeneous populations of small intestinal somatic cell hybrids selected for endogenous I-FABP expression (hBRIE 380i cells) demonstrated a 5-fold increase in I-FABP transcripts in response to PYY (within 6 h) that was confined to clusters of differentiated cells, whereas ribonuclease protection assays performed on heterogeneous populations of these cells showed no significant differences. High affinity PYY receptors, with an IC50 of 5–50 pm, were identified in both differentiated and nondifferentiated cell populations, as determined by competitive binding assays and autoradiography. In situ hybridization of rat ileal tissue also revealed differing patterns of mRNA expression for liver fatty acid-binding protein (L-FABP) and I-FABP. Only I-FABP mRNA was detected in the villus tips. This localization correlated with the expression pattern of I-FABP mRNA in the hBRIE 380i cells where changes in transcripts were observed only in differentiated cells that did not incorporate bromodeoxyuridine. The sustained expression of I-FABP transcripts in the villar tips suggests (unlike L-FABP) that older terminally differentiated cell populations of the mucosa can still be PYY responsive. These studies demonstrate that physiological concentrations of PYY can regulate I-FABP and place this peptide in a key position as part of a feedback system that determines the processing of cytosolic FFA in the enterocyte. In addition, these studies suggest a mechanism whereby luminal agents can modulate expression of proteins in terminally differentiated cells in the gastrointestinal mucosa. Peptide tyrosine tyrosine (PYY) 1The abbreviations used are: PYY, peptide tyrosine tyrosine; NPY, neuropeptide Y; PP, pancreatic polypeptide; FFA, free fatty acid; I-FABP and L-FABP, intestinal and liver fatty acid-binding proteins, respectively; BCS, bovine calf serum; RPA, ribonuclease protection assay; nt, nucleotide(s); BrdUrd, bromodeoxyuridine. 1The abbreviations used are: PYY, peptide tyrosine tyrosine; NPY, neuropeptide Y; PP, pancreatic polypeptide; FFA, free fatty acid; I-FABP and L-FABP, intestinal and liver fatty acid-binding proteins, respectively; BCS, bovine calf serum; RPA, ribonuclease protection assay; nt, nucleotide(s); BrdUrd, bromodeoxyuridine. is member of a 36-amino acid regulatory peptide family that includes neuropeptide Y (NPY) and pancreatic polypeptide (PP). PYY has greater than 70% sequence identity with NPY and shares a common structural motif consisting of two antiparallel helices, an amino-terminal polyproline helix, and a long amphipathic α helix connected by a β turn (1MacKerell Jr., A.D. J. Comput. Aided Mol. Des. 1988; 2: 55-63Crossref PubMed Scopus (31) cells in the small intestine and the where fatty acids can as of PYY the on the gastrointestinal can be by of the peptide concentrations than concentrations PubMed Scopus PubMed Scopus for in gastrointestinal as cells J. and mucosa of the small and intestine PubMed Scopus PYY also in tissue J. J. PubMed Scopus 1988; PubMed Scopus J. J. and in cell J. PubMed for PYY to both as an endocrine and a of the of PYY on the as the inhibition of intestinal and acid as with of PYY a and demonstrated that luminal acid the of PYY in the J. rat J. 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