Dietary Phosphate Influences Satellite Cell Activity and Subsequent Growth Potential in the Neonatal Pig

Satellite cells and mesenchymal stem cells (MSC) are critical to the growth and development of muscular and skeletal tissues. Satellite cells provide the myonuclei that allow for muscle fiber hypertrophy and MSC supply the osteoprogenitor cells responsible for skeletal growth. Despite the impact of dietary phosphate (PO4) on muscular and skeletal tissue growth, relatively little research has examined the impact of PO4 nutrition during the neonatal period when there is the highest number of satellite cells in muscle and MSC in bone marrow. The objective of the following experiments was to examine the possibility of nutritional programming of tissue specific stem cell activity by dietary PO4.;In the first experiment 20 piglets obtained at 24 h of age, were allotted into 1 of 2 treatment groups and were pair-fed, a soy-based liquid milk replacer that either met PO4 requirements or was approximately 25% deficient in available PO4 over 15 d. Lower sera PO4 and PTH concentrations were observed (P < 0.05) in PO4 restriction. Phosphate deficiency reduced growth (P < 0.05), feed efficiency (P < 0.05), bone mineral content (P < 0.05) and stem cell proliferation (P < 0.05). Dietary PO 4 impacted expression of genes associated with adipogeneis and osteogenesis in bone marrow and those associated with vitamin D metabolism in the kidney. We demonstrated that dietary PO4 deficiency reduces in vivo proliferation of stem cells, suggesting that dietary PO4 during early post-natal development can impact future growth potential by influencing stem cell activity.;The PO4 requirement of the neonatal pig is unknown, therefore a second experiment was performed to determine how differing inclusion levels of PO4 into the neonatal diet impacted stem cell kinetics. Twenty-one male and female piglets were obtained at 24 h of age and allotted into 1 of 3 dietary treatment groups. Pigs were pair-fed a milk-replacer diet that was either PO4 adequate, 25% in excess of the PO4 requirement, or 25% deficient in PO4 content for 12 d. Excess dietary PO 4 increased sera PO4 and PTH (P < 0.05) concentrations and improved (P < 0.05) feed conversion efficiency. Dietary PO4 deficiency resulted in wider bones (P < 0.05) with lesser dry matter percentages (P < 0.05). Excess dietary PO4 increased proliferation of MSC (P < 0.05) but not satellite cells. Expression of those genes associated with osteogenesis in bone marrow and Ca and P regulation in the thyroid were affected by dietary PO4. It was determined that access to provision of PO4 that is more available and in excess of what is supplied by the sow may have potential beneficial effects on stem cell activity and subsequent growth.;In the final experiment, satellite cells isolated from pigs in Experiment 2 were cultured in proliferating and differentiating media over 7 d to determine the impact of dietary PO4 on satellite cell progression through the myogenic lineage. Increased proliferation was noted in cells from PO 4 excess pigs. Immunofluorescent staining for Pax7, MyoD, and myogenin demonstrated increases in positive staining for all 3 proteins between 3 d and 5 d, but decreased by 7 d. Cells isolated from PO4 excess pigs had greater (P < 0.05) DNA:protein content at 5 d, though DNA:protein content was higher in cells from PO4 deficient pigsby 7 d. Increased MyoD and myogenin gene expression (P < 0.05) were noted at 7 d in cells from PO4 deficient pigs. These data are suggestive of possible premature differentiation of satellite cells during PO4 restriction.;From these experiments it can be concluded that early life dietary PO 4 influences tissue specific stem cell activity by triggering a nutritional programming event that permanently alters the behavior of these cells. Gaining an understanding of how early life nutrition impacts muscle and bone growth will allow us to clarify the possible long-term effects on growth potential in the pig.