Post-Transcriptional Processing of the Small Intestinal Alkaline Phosphatase in the Postnatal Developing Pig

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Efficiency of whole body energy and nutrient utilization is high at birth and during suckling, then drops dramatically during the weanling transition and becomes low during the post-weaning growth in pigs. Weaning-associated enteric diseases and growth retardation are major challenges facing the current global swine production. Current use of feed antibiotics for curbing morbidity and mortality in weanling swine nutrition contributes to the rising global public health threat associated with antibiotic resistance. Long-term goals of my NSERC Discovery program aim to understand the expression and regulatory factors of the small intestinal hydrolases and nutrient transporters in affecting gut functions along the crypt-villus axis and during the gut development in pigs. Weaning marks a major intestinal adaptation from suckling to feeding on solid diets in mammals. Intestinal alkaline phosphatase (IAP) is an abundant apical membrane protein with a primary physiological function of detoxification of bacterial endotoxin lipopolysaccharides. Thus, expression of IAP is pivotal in protecting the gut from inflammation and infection and in maintaining whole body health status. Early weaning dampens the IAP maximal enzyme activity by reducing the IAP gene expression at the transcriptional and post-transcriptional levels with considerable decreases in the apical IAP abundance and affinity in piglets. Enteral amino acid (AA) availability and dietary prebiotics could modulate IAP expression and functionality. I hypothesize that IAP expression, functionality and enteral health status in weanling piglets fed a low-protein diet could be substantially enhanced by post-transcriptional regulation of IAP biosynthesis and IAP glycosylation because of increases in dietary supply of trophic AA, i.e., crystalline glutamate, glutamine, leucine and selected fermentable non-viscous soluble fibres serving as prebiotics. Specific objectives for the proposed research are to investigate roles of increasing these trophic dietary AA availability and changing the selected non-viscous soluble fibre composition in regulating the jejunal IAP fractional synthesis rate and IAP functionality, and in supporting two graduate students to conduct the proposed research. Major methodology for the proposed research includes IAP kinetics measured with chromogenic and purified physiological substrates, in vivo IAP fractional synthesis rate by isotopic labeling, IAP glycosylation by immune-precipitation and chemical profiling, and intestinal protein translational pathway initiation and elongation factor abundances by Western blotting. The proposed research will contribute to improved understanding of dietary factors in up-regulating intestinal endogenous alkaline phosphatase expression and functionality and the development of alternative strategies to improve gut health in weanling pigs.**