Using an HDAC Inhibitor to Alter Muscle Growth in Fetal Pigs

Abstract

A broad spectrum histone deacetylase (HDAC) inhibitor, butyrate, has been shown to promote increased myofiber size by altering satellite cell (SC) activity. The use of dietary supplementation of butyrate to affect muscle development has been hampered by its technical and pharmacokinetic properties. Most of these can be overcome with the use of tributyrin (TB), a butyrate prodrug. Dietary supplementation of TB was able to promote muscle growth by increasing myofiber size in neonatal pigs. We hypothesized that muscle growth during fetal development may be improved by increased fiber number through the dietary supplementation of TB to gestating sows. Nine sows of 53.6 ±1.08 gestational days (gd) were randomly assigned to one of three dietary treatment groups (n=3). These dietary treatments were a basal diet, basal diet + 1% TB, and the basal diet + 2% TB. All diets were made isocaloric with the addition of oil and wheat flour. Fetal piglets were removed at 107.6 ±1.5 gd. Weights and body lengths were recorded for all fetuses. Sections of Longissimus dorsi and Psoas major were collected from the median male, median female, the smallest, and the largest piglets of each litter and frozen for future histological analysis. Two novel methods for objective description of muscle fiber organization were evaluated, including fiber eccentricity (measure of elongation), and proportion of primary myofibers. The most significant difference in cross sectional area (CSA) was found within LD muscle with TB supplementation causing a significant reduction compared to control animals (p value < 0.05). Fibers from 1% TB animals were significantly more elongated than control (p value < 0.05). The proportion of primary to secondary myofibers was significantly higher in muscle from 2% TB treated piglets compared to control (p value < 0.05). The smaller CSA together with a similar body weight across individual piglets (p >0.05) suggest that TB supplementation increased myofiber number. The increased fiber count may be further supported by more elongated myofibers suggesting alterations to muscle fiber organization and an improved development of primary fibers. Further studies to elucidate the impact of TB supplementation during gestation and early postnatal life are warranted.