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

Impact of pre-breeding feeding practices on rabbit mammary gland development at mid-pregnancy

AbstractOptimizing rabbit does preparation during early life to improve reproductive potential is a major challenge for breeders. Does selected for reproduction have specific nutritional needs, which may not be supplied with the common practice of feed restriction during rearing in commercial rabbit production. Nutrition during early life was already known to influence metabolism, reproduction and mammary gland development later in life, in particular during pregnancy. The aim of this study was to analyze the impact of four different feeding strategies in the early life of rabbit females (combination of high or moderate feed restriction from 5 to 9 weeks of age with restricted or ad libitum feeding regime from 9 to 12 weeks of constituting the pubertal period) on their growth, reproductive capacities and mammary development at mid-pregnancy.Unlike food intake, which remains regular, mean body weight gain was inversely proportional to the dietary restriction applied over the considered periods. The feeding strategies in place for the four groups had no effect on the reproductive parameters of the females at mid-pregnancy, as opposed to certain metabolic parameters such as cholesterolemia, that decreased with dietary intake at puberty (p≤0.05). Furthermore, restriction programs have impacted mammary tissular structures at mid-pregnancy. The expression of lipid metabolism enzymes (Fatty acid synthase N and Stearoyl co-A desaturase) is also increased in mammary epithelial tissue at mid-pregnancy by the dietary strategies implemented (p≤0.05). Moreover, milk gene expression, used as differentiation markers, indicates a better mammary epithelial development regarding further lactation, in the case of the less restrictive strategies during early life period, especially the higher feeding allowance. Our results highlight the importance of investigating feeding conditions of young female rabbits and nutrition in early life rearing, in order to provide specific recommendations for optimizing lactation and thus preventing neonatal mortality of the offspring.</jats:p

Sow environment during gestation. Part II. Influence on piglet physiology and tissue maturity at birth

International audienceSow environment during gestation can generate maternal stress which could alter foetal development. The effects of two group-housing systems for gestating sows on piglet morphological and physiological traits at birth were investigated. During gestation, sows were reared in a conventional system on a slatted floor (C, 18 sows), demonstrated as being stressful for sows or in an enriched system in larger pens and on deep straw bedding (E, 19 sows). On gestation day 105, sows were transferred into identical individual farrowing crates on a slatted floor. Farrowing was supervised to allow sampling from piglets at birth. In each litter, one male piglet of average birth weight was euthanized immediately after birth to study organ development and tissue traits. Blood samples were collected from 6 or 7 piglets per litter at birth and 2 piglets per litter at 4 days of lactation (DL4). At birth, mean piglet BW did not differ between groups (P > 0.10); however, the percentage of light ( 0.10) between C and E piglets, but the insulin to glucose ratio was greater (P = 0.02) in C than in E piglets. Compared with E piglets, C piglets had a lighter gut at birth (P = 0.01) and their glycogen content in longissimus muscle was lower (P < 0.01). In this muscle, messenger RNA levels of PAX7, a marker of satellite cells and of PPARGC1A, a transcriptional coactivator involved in mitochondriogenesis and mitochondrial energy metabolism, were greater (P < 0.05), whereas the expression level of PRDX6, a gene playing a role in antioxidant pathway, was lower (P = 0.03) in C than in E piglets. Other studied genes involved in myogenesis did not differ between C and E piglets. No system effect was observed on target genes in liver and subcutaneous adipose tissue. On DL4, C piglets exhibited a lower plasma antioxidant capacity than E piglets (P = 0.002). In conclusion, exposure of sows to a stressful environment during gestation had mild negative effects on the maturity of piglets at birth

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