Rescue of Dystrophic Skeletal Muscle by PGC-1α Involves a Fast to Slow Fiber Type Shift in the mdx Mouse

Increased utrophin expression is known to reduce pathology in dystrophin-deficient skeletal muscles. Transgenic over-expression of PGC-1α has been shown to increase levels of utrophin mRNA and improve the histology of mdx muscles. Other reports have shown that PGC-1α signaling can lead to increased oxidative capacity and a fast to slow fiber type shift. Given that it has been shown that slow fibers produce and maintain more utrophin than fast skeletal muscle fibers, we hypothesized that over-expression of PGC-1α in post-natal mdx mice would increase utrophin levels via a fiber type shift, resulting in more slow, oxidative fibers that are also more resistant to contraction-induced damage. To test this hypothesis, neonatal mdx mice were injected with recombinant adeno-associated virus (AAV) driving expression of PGC-1α. PGC-1α over-expression resulted in increased utrophin and type I myosin heavy chain expression as well as elevated mitochondrial protein expression. Muscles were shown to be more resistant to contraction-induced damage and more fatigue resistant. Sirt-1 was increased while p38 activation and NRF-1 were reduced in PGC-1α over-expressing muscle when compared to control. We also evaluated if the use a pharmacological PGC-1α pathway activator, resveratrol, could drive the same physiological changes. Resveratrol administration (100 mg/kg/day) resulted in improved fatigue resistance, but did not achieve significant increases in utrophin expression. These data suggest that the PGC-1α pathway is a potential target for therapeutic intervention in dystrophic skeletal muscle

Effect of environmental enrichment with wood materials and straw pellets on the metabolic status of sows during gestation

Environmental enrichment is a recognized strategy to improve sow welfare. Providing manipulable wood materials and straw pellets to sows during gestation might participate in satisfying their investigative behavior. Sows may also get a benefit from chewing and eating fibers, which can decrease their hunger. Such strategy, however, should not adversely affect metabolic status of sows and newborn piglets. In this study, gestating sows were group-housed in a conventional system on slatted floor (C, n = 26) or in the same system enriched with pieces of oak attached to a chain and straw pellets (CE, n = 30). Straw pellets were provided in the trough at a rate of 200 g/d from 3 to 30 days of gestation (DG) and 400 g/d from 31 to 104 DG. On DG105, sows were transferred into farrowing pens and housed in identical individual stalls on slatted floor. Sow body weight and backfat thickness were recorded before insemination, on DG105 and at weaning. Plasma concentrations of metabolites and insulin were measured in sows on DG73 and DG102. Blood was also collected from a subset of piglets at birth (n = 6 per litter in 5 C and 8 CE litters) to determine their metabolic and oxidative status. Sow body weight, backfat thickness, and estimated body lipid and protein masses did not differ between treatments during gestation and lactation. Maternal plasma concentrations of glucose, lactate, NEFA, beta‑hydroxy‑butyrate and insulin did not differ between groups (P > 0.10). However, CE sows had lower circulating concentrations of urea (P 0.10) piglet birth weight or plasma concentrations of glucose, fructose, lactate and albumin, antioxidant potential and the oxidative stress index in newborns. On the day after farrowing, the milk produced by CE sows contained more minerals (P < 0.01) than the milk of C sows but similar contents of protein, fat, lactose, energy and IgA. The proportion of piglets that died at birth and within 12 h of birth was lower in CE than in C litters (P < 0.05), but overall mortality (stillbirth + preweaning death) did not differ between the two groups. To conclude, providing manipulable materials and straw pellets to sows during gestation had little impact on sow metabolic status but improved early neonatal survival