Testosterone stimulates extra‐hepatic but not hepatic fat oxidation (Fox): comparison of oral and transdermal testosterone administration in hypopituitary men

Birzniece, Vita; Meinhardt, Udo; Handelsman, David J.

doi:10.1111/j.1365-2265.2009.03524.x

Cited by 26 publications

(53 citation statements)

References 50 publications

(107 reference statements)

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“…In the present study, our results suggested a beneficial role of testosterone therapy in aging men with low normal bioavailable testosterone levels on one component of metabolic flexibility as indicated by the increase in lipid oxidation and decrease in glucose oxidation during fasting. This is in agreement with reports of decreased lipid oxidation in men with very low levels of testosterone, i.e., hypogonadism due to pituitary disease (Birzniece et al 2009). In human skeletal muscle, lipid is the predominate oxidative substrate during fasting, accounting for approximately 80% of oxygen consumption (Dagenais et al 1976).…”

Section: Discussionsupporting

confidence: 93%

Testosterone therapy increased muscle mass and lipid oxidation in aging men

Frederiksen

Højlund

Hougaard

et al. 2011

AGE

115

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The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebocontrolled study of testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b=1.9 kg, p=0.003) increased while HDL-cholesterol (b=−0.12 mmol/l, p=0.043) and TFM decreased (b=−1.2 kg, p=0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b=5.65 mg/min/m 2 , p=0.045) increased and basal glucose oxidation (b=−9.71 mg/min/m 2 , p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b=−0.01mg/min/m 2 , p=0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.

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Section: Discussionsupporting

confidence: 93%

Testosterone therapy increased muscle mass and lipid oxidation in aging men

Frederiksen

Højlund

Hougaard

et al. 2011

AGE

115

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“…Moreover, we have recently shown that testosterone therapy promoted a shift in substrate partitioning toward an increased lipid oxidation and decreased glucose oxidation in elderly men with subnormal bioavailable testosterone levels (4). Consistently, other studies have reported that testosterone therapy stimulates lipid oxidation in hypopituitary men (20,21), and that testosterone deficiency, induced by a gonadotropin-releasing hormone analog in younger men, increases adiposity and decreases fat oxidation and resting energy expenditure (22). The possible effect of testosterone on energy metabolism is supported by a recent microarray study of orchidectomized mice, in which testosterone replacement in addition to the known positive effects on muscle mass and insulin-like growth factor 1/Akt signaling also normalized the expression of OxPhos genes (3,23).…”

Section: Introductionsupporting

confidence: 59%

“…This suggested that the positive effect of testosterone on lipid oxidation reported in humans (4,20,21,22) could be mediated by the AR in skeletal muscle. Accordingly, it has been reported that the testosterone-mediated stimulation of whole-body lipid oxidation is not due to an increase in liver lipid oxidation, but rather takes place in peripheral tissues such as skeletal muscle (20). As reported in other clinical trials (1, 2, 3, 4), we found a modest but significant increase in muscle mass (LBM) and a reciprocal decrease in adiposity in response to testosterone therapy.…”

Section: Discussionmentioning

confidence: 90%

“…A recent study of myotubes from male donors has shown that the testosterone-mediated increase in palmitate oxidation was attenuated in the presence of an AR antagonist (24). This suggested that the positive effect of testosterone on lipid oxidation reported in humans (4,20,21,22) could be mediated by the AR in skeletal muscle. Accordingly, it has been reported that the testosterone-mediated stimulation of whole-body lipid oxidation is not due to an increase in liver lipid oxidation, but rather takes place in peripheral tissues such as skeletal muscle (20).…”

Section: Discussionmentioning

confidence: 94%

“…Recent studies have indicated a link between testosterone, insulin sensitivity, and mitochondrial oxidative capacity, including lipid oxidation (4,19,20,21,22,23,24). We hypothesized that testosterone therapy, which is known to cause favorable changes in body composition, would stimulate mitochondrial biogenesis and lead to increased abundance of molecular markers of OxPhos and lipid metabolism in skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

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

Petersson

Christensen

Kristensen

et al. 2014

European Journal of Endocrinology

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Objective: Recent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. Methods: Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (nZ12) or placebo (nZ13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting. Results: Despite an increase in lipid oxidation (P!0.05), testosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, PRKAA2, and PRKAG3), OxPhos (NDUFS1, ETFA, SDHA, UQCRC1, and COX5B), or lipid metabolism (ACADVL, CD36, CPT1B, HADH, and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear (SDHA and UQCRC1) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy. Conclusion: The beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.

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Consequences of the Use of Anabolic-Androgenic Steroids for Male Athletes’ Fertility

García-Manso

Valverde-Esteve

2016

Exercise and Human Reproduction

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Testosterone stimulates extra‐hepatic but not hepatic fat oxidation (Fox): comparison of oral and transdermal testosterone administration in hypopituitary men

Abstract: Short-term testosterone administration does not stimulate hepatic fat oxidation but enhances whole body fat oxidation by acting on extra-hepatic tissues.

Cited by 26 publications

References 50 publications

Testosterone therapy increased muscle mass and lipid oxidation in aging men

Testosterone therapy increased muscle mass and lipid oxidation in aging men

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

Consequences of the Use of Anabolic-Androgenic Steroids for Male Athletes’ Fertility

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