Dataset Information

Enhancement of muscle mitochondrial function by growth hormone.

ABSTRACT: Although GH promotes growth and protein anabolism, which are ATP-dependent processes, the GH effect on mitochondrial regulation remains to be determined.Our objective was to determine the acute effect of GH on mitochondrial oxidative capacity in skeletal muscle of healthy subjects.The study was a randomized crossover design at an academic medical center.Nine healthy men and women completed the study.GH (150 microg/h) or saline was infused for 14 h on separate days, and muscle biopsies were obtained.Outcome measures included mitochondrial function, gene expression, and protein metabolism.The 4-fold increase in plasma GH caused elevations in plasma IGF-I, insulin, glucose, and free fatty acids and a shift in fuel selection, with less carbohydrate (-69%) and leucine (-43%) oxidation and 29% more fat oxidation. Muscle mitochondrial ATP production rate and citrate synthase activity were increased 16-35% in response to GH. GH also resulted in higher abundance of muscle mRNAs encoding IGF-I, mitochondrial proteins from the nuclear (cytochrome c oxidase subunit 4) and mitochondrial (cytochrome c oxidase subunit 3) genomes, the nuclear-derived mitochondrial transcription factor A, and glucose transporter 4. Although GH increased whole-body protein synthesis (nonoxidative disposal of leucine), no effect on synthesis rate of muscle mitochondrial proteins was observed.These results demonstrate that acute GH action promotes an increase in mitochondrial oxidative capacity and abundance of several mitochondrial genes. These events may occur through direct or indirect effects of GH on intracellular signaling pathways but do not appear to involve a change in mitochondrial protein synthesis rate.

SUBMITTER: Short KR

PROVIDER: S-EPMC2243230 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enhancement of muscle mitochondrial function by growth hormone.

Short Kevin R KR Moller Niels N Bigelow Maureen L ML Coenen-Schimke Jill J Nair K Sreekumaran KS

The Journal of clinical endocrinology and metabolism 20071113 2

<h4>Context</h4>Although GH promotes growth and protein anabolism, which are ATP-dependent processes, the GH effect on mitochondrial regulation remains to be determined.<h4>Objective</h4>Our objective was to determine the acute effect of GH on mitochondrial oxidative capacity in skeletal muscle of healthy subjects.<h4>Design and setting</h4>The study was a randomized crossover design at an academic medical center.<h4>Participants</h4>Nine healthy men and women completed the study.<h4>Interventio ...[more]

PMID: 18000087

Similar Datasets

Project description:KEY POINTS:Skeletal muscle energy requirements increase at birth but little is known regarding the development of mitochondria that provide most of the cellular energy as ATP. Thyroid hormones are known regulators of adult metabolism and are important in driving several aspects of fetal development, including muscle fibre differentiation. Mitochondrial density and the abundance of mitochondrial membrane proteins in skeletal muscle increased during late gestation. However, mitochondrial functional capacity, measured as oxygen consumption rate, increased primarily after birth. Fetal hypothyroidism resulted in significant reductions in mitochondrial function and density in skeletal muscle before birth. Mitochondrial function matures towards birth and is dependent on the presence of thyroid hormones, with potential implications for the health of pre-term and hypothyroid infants. ABSTRACT:Birth is a significant metabolic challenge with exposure to a pro-oxidant environment and the increased energy demands for neonatal survival. This study investigated the development of mitochondrial density and activity in ovine biceps femoris skeletal muscle during the perinatal period and examined the role of thyroid hormones in these processes. Muscle capacity for oxidative phosphorylation increased primarily after birth but was accompanied by prepartum increases in mitochondrial density and the abundance of electron transfer system (ETS) complexes I-IV and ATP-synthase as well as by neonatal upregulation of uncoupling proteins. This temporal disparity between prepartum maturation and neonatal upregulation of mitochondrial oxidative capacity may protect against oxidative stress associated with birth while ensuring energy availability to the neonate. Fetal thyroid hormone deficiency reduced oxidative phosphorylation and prevented the prepartum upregulation of mitochondrial density and ETS proteins in fetal skeletal muscle. Overall, the data show that mitochondrial function matures over the perinatal period and is dependent on thyroid hormones, with potential consequences for neonatal viability and adult metabolic health.

Project description:BackgroundTesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown.ObjectivesThe goals of this exploratory secondary analysis were to determine the effects of tesamorelin on muscle quality (density) and quantity (area).DesignSecondary, exploratory analysis of two previously completed randomized (2:1), clinical trials.SettingU.S. and Canadian sites.ParticipantsPeople living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%).InterventionTesamorelin or placebo.MeasurementsComputed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm.ResultsTesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p<0.005), and the lean anterolateral/abdominal and rectus muscles (1.39 and 1.78 Hounsfield units; both p<0.005) compared to placebo. Significant increases were also seen in total area of the rectus and psoas muscles (0.44 and 0.46 centimeters2; p<0.005), and in the lean muscle area of all four truncal muscle groups (0.64-1.08 centimeters2; p<0.005).ConclusionsAmong those with clinically significant decrease in visceral adipose tissue on treatment, tesamorelin was effective in increasing skeletal muscle area and density. Long term effectiveness of tesamorelin among people with and without HIV, and the impact of these changes in daily life should be further studied.

Dataset Information

Enhancement of muscle mitochondrial function by growth hormone.

Publications

Enhancement of muscle mitochondrial function by growth hormone.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets