Project description:Intrauterine growth restriction (IUGR) is a leading cause of neonatal morbidity and mortality in humans and domestic animals. Developmental adaptations of skeletal muscle in IUGR lead to increased risk of premature muscle loss and metabolic disease later during life. Although transcriptome-wide profiles in muscle associated with IUGR have been reported, their regulation by miRNAs is not well understood. The aim of this study was to identify differences in miRNA expression in porcine skeletal muscle of IUGR and normal-weight (NW) littermates during late foetal development (day 90 of gestation).
Project description:Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation and reactive oxygen species scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1a is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1a activity. To test this model for the first time, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1a (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1a is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy demonstrated that PGC-1a is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1a is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1a nor mitochondrial biogenesis in skeletal muscle are required for the metabolic benefits of CR. Control (FLOX) and PGC-1a skeletal muscle specific knock out (MKO) mice were placed on a control diet [C] or a calorie restriction diet [CR] for 12 weeks. RNA was isolated from TA/EDL muscles for microarray analysis. The following numbers of mice were analyzed from each group: C FLOX: n = 6; C MKO: n = 7; CR FLOX: n = 6; CR MKO: n = 7. Mice were mixed C57/BL6 and 129 background.
Project description:The effects of recombinant human GDF15 on Sympathetic Nervous System (SNS) signalling in skeletal muscle during the caloric restriction in mice.
Project description:This study aimed to investigate the effect of glucose restriction (GR) on energy metabolism and muscle fibre type in skeletal muscle. To achieve this goal, we constructed a mouse model of innate glucose restriction by mutating the glucose transporter 4 (Glut4), the major glucose transporter in skeletal muscle. We performed proteomic and phosphoproteomic analysis on gastrocnemius samples of male Glut4m mice at 12-week age, with or without a 4-week low-intensity training.
Project description:The aim of this study was to identify genes, gene clusters and networks involved in sexual dimorphism and in the response to nutritional restriction in porcine skeletal muscles, through the analysis of gene expression differences. Full sib Iberian piglets from three litters composed of two males and two females per family were randomly assigned to two dietary treatments which differed in the feeding level during 15 wk. At the end of the trial, 27 wk of age, significant phenotypic differences were detected between genders and between feeding levels for growth, fatness, fatty acid composition and primary cuts weights. RNA samples from two skeletal muscles, diaphragm and Psoas major, were hybridized with Affymetrix microarrays and the expression data were analyzed using a mixed model and a FDR<0.01. The successfully performed validations by qRT-PCR of six selected genes supported the reliability of our microarray results. Ina a first step, the main gene expression differences between both muscles were established, identifying 181 differentially expressed genes, which represented almost exclusively anatomical structural differences. The analysis between genders reported expression differences of 59 unique genes, mainly implicated in muscle growth and stress response, including well known genes, such as IGF1, apart from others potentially associated to meat quality such as ANKRD1. The analysis of the feeding level effect restriction reported up-regulation of 76 genes and down-regulation of other 60 genes. Functional annotation showed that the moderated nutritional restriction applied led to a reduced growth through down-regulation of key genes implicated in enhancing growth and up-regulation of genes implicated in inhibiting growth. Besides, the restriction led to an increase of muscular aminoacid metabolism and decrease of lipid metabolism as adaptive response. Changes in expression patterns of genes determining meat characteristics, such as PDK4 implicated in water holding, CTSD associated to muscle transformation during meat processing and SCD involved in the determination of fatty acids profiles, were also reported. Finally, we identify relevant expression differences in ADAM12, CA2, UCHL1 and ESRRG genes, which are involved in human obesity and have not been previously studied in pig. 16 skeletal muscle samples, diaphragm and psoas major, from eight animals at slaughter, 211 days old, four males and four females, four under high feeding level and four under 20% restriction.
Project description:Skeletal muscle unloading due to joint immobilization induces skeletal muscle atrophy. However, the skeletal muscle proteome response to limb immobilization has not been investigated using SWATH methods. This study quantitatively characterized the muscle proteome at baseline, and after 3 and 14 d of unilateral lower limb (knee-brace) immobilization in 18 healthy young men (25.4 ±5.5 y, 81.2 ±11.6 kg). All muscle biopsies were obtained from the vastus lateralis muscle. Unilateral lower limb immobilization was preceded by four-weeks of exercise training to standardise acute training history, and 7 days of dietary provision to standardise energy/macronutrient intake. Dietary intake was also standardised/provided throughout the 14 d immobilization period.
Project description:The objective of this study was to examine changes in muscle gene expression of growing bulls during a period of dietary energy restriction followed by a period of subsequent realimentation and compensatory growth. Purebred Holstein Friesian bulls (n=20) were assigned to one of two feeding treatments (i) restricted feed allowance for 125 days (n=10) followed by ad libitum access to feed for a further 55 days or (ii) a control group with ad libitum access to feed through out the 180 days trial (n=10). The first 125 days of the trial were denoted as Peirod 1, during which treatment groups were fed differentially. The subsequent 55 days, denoted as Period 2 during which all bulls were fed ad libitum. All bulls received the same diet of 70% concentrate 30% grass silage through out the experimental trial,with the amount of feed provided different dependnet on each treatment group. Muscle biopsies were collected at 2 time points (end of the differential feeding in Period 1 (d 120) and during the realimentation phase in Period 2 (d 15 of re-alimentation). RNA was extracted and muscle gene expression was examined using RNAseq technology and bioinformatic analysis. During the differential feeding period, over-represented pathways including fatty acid beta oxidaiton, oxidative phosphorylation and TCA cyclewere identified, which indicate utilisation of lipid sotes for energy utilisaiton and also alterations in energy produciton during dietary restriciton in muscle. During the realimentation period, pathways involved in energy produciton were over-represented, with the direction of fold changes opposite to that of these pathways in Period 1. additionally, a number of genes involved in cell division and cellular proliferation were up-regulated during compensatory growth in re-alimentation, thereby promoting accelerated cell growth and proliferation in muscle tissue of animals experiencing compensatory growth. This information can be exploited in genomic breeding programmes to assist selection of cattle with a greater ability to compensate following a period dietary restriction. 40 muscle RNA samples were analysed in total. 10 samples were from muscle biopsies collected at the end of a period of dietary restriction (d 120) and 10 samples were from muscle biopsis collected during the initial stages of compensatory growth (d 15 of re-alimentation). In addition, RNA was also anlaysed from 10 samples collected from animals fed a libitum at each of these two timepoints.
Project description:In utero undernutrition is associated with obesity and insulin resistance, although its effect on skeletal muscle remains poorly defined. We report that, in mice, adult offspring from undernourished dams have decreased energy expenditure, decreased skeletal muscle mitochondrial content, and altered energetics in isolated mitochondria and permeabilized muscle fibers. Strikingly, when these mice are put on a 40% calorie restricted diet they lose half as much weight as calorie restricted controls. Our results reveal for the first time that in utero undernutrition alters metabolic physiology having a profound effect on skeletal muscle energetics and response to calorie restriction in adulthood. We have used a mouse model of low birth weight generated through 50% food restriction of mouse dams during the third week of gestation. We have studied in utero food restricted offspring and control offspring that were not food restricted in utero in both the ad libitum and calorie restricted states. Gene expression profiling was performed on tibialis anterior muscle from 8 mice per group, pooled in pairs.