Tributyrin Supplementation to Neonatal Piglets Enhances Muscle Growth through Modified Satellite Cell Behavior

The sustainability of the swine production relies on efficient lean growth. Postnatal muscle growth is dependent on myonuclear accretion and subsequent protein accumulation. Altering the ability of muscle resident stem cells (satellite cells, SC), which provide for nuclear accretion, to progress through their myogenic lineage can have lifelong effects on muscle growth. The use of butyrate, a histone deacetylase (HDAC) inhibitor, has promoted satellite cell myogenesis in vitro. In animal models, dietary butyrate has improved growth performance, but the impact of dietary butyrate on SC activity and the direct promotion of muscle growth have not been examined. In two studies, we utilized dietary tributyrin, a prodrug of butyrate, to examine the potential of butyrate as a muscle growth promoter in neonatal piglets. Study 1, 30 neonatal piglets (24±6h old) were fed a commercial milk replacer supplemented with 0.25% or 0.5% butyric acid (on a dry matter basis) in the form of tributyrin for 20d. Muscle tissue and SC were then harvested from the Longissimus dorsi (LD) to assess muscle growth and SC myogenesis. Tributyrin treatment increased the myogenic potential of SC based on increased myotube formation and an upregulation of myogenin gene expression. Also, piglets receiving the higher dietary tributyrin inclusion rate had significantly increased myonuclear accretion (P<.05), further indicating the potential for enhanced muscle growth. However, at the end of this study, there were no significant improvements in growth performance parameters. In order to further assess muscle growth potential, tributyrin supplementation during the pre-weaning and nursery phases was examined in a 2x2 factorial design. Piglets (30, 24±6h old) received milk replacer with or without tributyrin (0.5% butyric acid) for 20d then were weaned onto a dry diet either with or without tributyrin for 37d. At trial completion (58d of age), LD muscle samples were collected at the 12^th rib to assess muscle growth. Piglets who received tributyrin during the neonatal phase had 8% greater final body weight (P<.05) and a 9% increase in overall ADG (P<.05). These piglets also had larger loin eye area and greater muscle fiber cross-sectional area (assessed by immunohistochemical staining) (P<.05). Tributyrin treatment in the nursery phase did not have a significant effect on muscle growth or feed efficiency. Previous studies have attributed the beneficial growth effects of butyrate supplementation on improved intestinal health; however, our findings suggest that tributyrin is also potent promoter of muscle growth via enhanced satellite cell myogenic potential.