Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of Duchenne muscular dystrophy

The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles

Myogenin Regulates Exercise Capacity and Skeletal Muscle Metabolism in the Adult Mouse

Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle

Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)

Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10-12) and small (3-4) litter sizes, of Brandt's voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China.Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters.These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood

Ablations of Ghrelin and Ghrelin Receptor Exhibit Differential Metabolic Phenotypes and Thermogenic Capacity during Aging

mice are adaptive. mice.Our data therefore suggest that GHS-R ablation activates adaptive thermogenic function(s) in BAT and increases EE, thereby enabling the retention of a lean phenotype. This is the first direct evidence that the ghrelin signaling pathway regulates fat-burning BAT to affect energy balance during aging. This regulation is likely mediated through an as-yet-unidentified new ligand of GHS-R

SULLE CARATTERISTICHE DEL FLUSSO IN CORRISPONDENZA DI UN PENNELLO

L'ACQU

Non conforming finite element model to analyse highly non-linear groundwater problems: the case of Richard's equation

Analytical solutions of the Richards equation for unsaturated flow with varying boundary and initial conditions are difficult to obtain because of nonlinearity in soil hydraulic parameters. This difficulty is exaggerated in the case where soil is heterogeneous. Generally, one has to rely on numerical approaches for predicting moisture movement in unsaturated soils. In this paper the capability of the non-conforming quadrilateral finite element for solving saturated-unsaturated porous media seepage problems is presented. The reliability of the proposed model is checked by comparing the numerical solutions with the analytical solutions available in literature. The accuracy of the numerical solution with increasing element dimensions is examined to find out the proper mesh size compatible with the scale of practical interest in civil engineering problems where unsaturated flow plays an important role

A study on surface finishing and weld line strength in micro injection moulding using a variotherm and visual mould

In temperature cycle injection moulding (TCIM) of thermoplastics, the mould cavity surface is heated to a temperature close to the glass transition point of the resin before melt injection, and then cooled after injection is complete. In order to study the weld line developing process and its influence on surface finish in micro injection moulding, a variotherm system mould was used. The effect of TCIM on mechanical properties in the region of the weld line is also the subject of the present work. In this mould, a visualization design was integrated. A tensile bar sample and a flat cavity with an obstacle were used for the study of two main types of weld line. The tensile specimens were produced applying different processing parameters. Weld line depth and surface roughness are determined using an atomic force microscope. Weld line strength of micro tensile samples were tested on the micro tensile test machine. Results showed that the shape of weld lines and roughness are mainly influenced by mould temperature and its interaction with the injection speed. It is necessary to increase the temperature to 10\ub0C higher than Tg to obtain a glossy surface without weld lines. The cooling time of the injected part also affects the weld line depth. Elevated mould temperature and low injection speed were shown to improve weld line strength for each material in the experiment. Weld line strength was shown to be inversely proportional to the impingement velocity. Candidate reasons include air entrainment in the mating surface and superheating of the air compressed air in the region affecting the polymer behavior. The comparison between conventional injection moulding process and TCIM shows how the variotherm system is suitable to be used to improve the mechanical properties and to completely remove the weld lines of plastic parts