Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

Petersson, Stine Juhl; Christensen, Louise Lehmann; Kristensen, Jonas M.; Kruse, Rikke; Andersen, Marianne; Højlund, Kurt

doi:10.1530/eje-14-0006

Cited by 32 publications

(26 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Study in human muscle biopsy following testosterone therapy indicated that Ppia, Polymerase (RNA) II Subunit A (POLR2A) and Importin 8 (IPO8) were identified as suitable RG [20]. Even though HPRT is a variable gene among the examined set of genes under the influence of testosterone, unpublished data from our lab have identified GAPDH and HPRT as suitable RG in the uterus under the influence of estradiol in mature WKY rat.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of some housekeeping genes [9,17], such as tubulin, cyclophilin, tyrosine aminotransferase, ACTB, GAPDH and 18S in the liver of intact female and male rats, was shown to be sex-dependent as their levels of expression were different in both genders [18]. In a study by Cai et al [19] ACTB was used as a RGs following castration in pig, whilst in another study in aging men Polymerase (RNA) II Subunit A (POLR2A), Importin 8 (IPO8) and Ppia were identified as suitable genes for data analysis in biopsies of skeletal muscle following testosterone therapy [20]. There was no study to report of expression of housekeeping genes under the influence of testosterone in rats.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

et al. 2017

View full text Add to dashboard Cite

Real-time quantitative PCR (qPCR) is the most reliable and accurate technique for analyses of gene expression. Endogenous reference genes are being used to normalize qPCR data even though their expression may vary under different conditions and in different tissues. Nonetheless, verification of expression of reference genes in selected studied tissue is essential in order to accurately assess the level of expression of target genes of interest. Therefore, in this study, we attempted to examine six commonly used reference genes in order to identify the gene being expressed most constantly under the influence of testosterone in the kidneys and hypothalamus. The reference genes include glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin beta (ACTB), beta-2 microglobulin (B2m), hypoxanthine phosphoribosyltransferase 1 (HPRT), peptidylprolylisomerase A (Ppia) and hydroxymethylbilane synthase (Hmbs). The cycle threshold (Ct) value for each gene was determined and data obtained were analyzed using the software programs NormFinder, geNorm, BestKeeper, and rank aggregation. Results showed that Hmbs and Ppia genes were the most stably expressed in the hypothalamus. Meanwhile, in kidneys, Hmbs and GAPDH appeared to be the most constant genes. In conclusion, variations in expression levels of reference genes occur in kidneys and hypothalamus under similar conditions; thus, it is important to verify reference gene levels in these tissues prior to commencing any studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The largest difference in gene expression between normal and diabetic muscle was ubiquinol cytochrome c reductase binding protein that plays a critical role in OxPhos, and this expression was correlated with testosterone and insulin resistance . Testosterone replacement for 6 months in men with subnormal bioavailable testosterone levels increased lipid oxidation in muscle biopsies, although the expression of mitochondrial OxPhos genes was not altered . TRT in men with low free testosterone leads to an increase in lipid oxidation and a decrease in glucose oxidation, suggesting a shift in substrate partitioning to favour lipid utilization .…”

Section: Testosterone Mechanisms In Obesitymentioning

confidence: 96%

Testosterone and obesity

2015

View full text Add to dashboard Cite

Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal-obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism.

show abstract

“…Usui et al (28) demonstrated that in mice, testosterone treatment resulted in an increase in heat production that the authors concluded was derived from elevated mitochondrial biogenesis in skeletal muscle. On the other hand, in hypogonadal men treated with testosterone, Petersson et al (19) observed no effect on insulin sensitivity or skeletal muscle mRNA levels of genes involved in mitochondrial biogenesis, oxidative phosphorylation, or lipid metabolism. We observed a small but significant increase in muscle mitochondrial protein FSR.…”

Section: E414 Fractional Synthesis Rates Of Skeletal Muscle Proteinsmentioning

confidence: 99%

Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats

Shankaran

Shearer

Stimpson

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

. Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats. Am J Physiol Endocrinol Metab 310: E405-E417, 2016. First published December 29, 2015 doi:10.1152/ajpendo.00257.2015.-Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167-201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated (r 2 ϭ 0.90 -0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate-to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM. fractional synthesis rate; protein synthesis; selective androgen receptor modulator; skeletal muscle; anabolism; dynamic proteomics; stable isotope; biomarkers of muscle anabolism LOSS OF SKELETAL MUSCLE MASS with age (sarcopenia) or chronic disease (cachexia) is associated with reduced functional capacity, disability, and increased mortality (8). Androgen receptor (AR) stimulation via testosterone or other anabolic steroids is an established intervention for increasing muscle mass, strength, and functional performance in a dose-responsive way in many clinical settings (3, 15). Selective androgen receptor modulators (SARMs) represent a promising class of smallmolecule therapeutics for stimulating muscle anabolism through AR activation. SARM molecules have been under development for decades, and several compounds have proven to be effective at increasing muscle mass in several animal models and in humans (2,16,31).AR stimulation increases muscle mass primarily by increasing the synthesis rates of muscle proteins (10, 11). Changes in muscle mass or function that may result from an anabolic agent are also related to a number of addit...

show abstract

Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

Cited by 32 publications

References 46 publications

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

Testosterone and obesity

Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats

Contact Info

Product

Resources

About