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      Effects of systemic hypoxia on human muscular adaptations to resistance exercise training

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          Abstract

          Hypoxia is an important modulator of endurance exercise‐induced oxidative adaptations in skeletal muscle. However, whether hypoxia affects resistance exercise‐induced muscle adaptations remains unknown. Here, we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training, including muscle cross‐sectional area (CSA), one‐repetition maximum (1RM), muscular endurance, and makers of mitochondrial biogenesis and angiogenesis, such as peroxisome proliferator‐activated receptor‐ γ coactivator‐1 α (PGC‐1 α), citrate synthase (CS) activity, nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), hypoxia‐inducible factor‐1 (HIF‐1), and capillary‐to‐fiber ratio. Sixteen healthy male subjects were randomly assigned to either a normoxic resistance training group (NRT, n =7) or a hypoxic (14.4% oxygen) resistance training group (HRT, n =9) and performed 8 weeks of resistance training. Blood and muscle biopsy samples were obtained before and after training. After training muscle CSA of the femoral region, 1RM for bench‐press and leg‐press, muscular endurance, and skeletal muscle VEGF protein levels significantly increased in both groups. The increase in muscular endurance was significantly higher in the HRT group. Plasma VEGF concentration and skeletal muscle capillary‐to‐fiber ratio were significantly higher in the HRT group than the NRT group following training. Our results suggest that, in addition to increases in muscle size and strength, HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle.

          Abstract

          This study investigated the effect of resistance exercise training performed under systemic hypoxia or normoxia on biochemical and molecular muscular adaptations in healthy male subjects. Our findings demonstrate that resistance training under systemic hypoxia led not only muscle hypertrophy, but most interestingly, to a greater increase in muscular endurance. This increase in muscular endurance was potentially caused by the increased angiogenesis as determined by capillary‐to‐fiber ratio.

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          Most cited references28

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          Percutaneous needle biopsy of skeletal muscle in physiological and clinical research.

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            HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha.

            Ischaemia of the heart, brain and limbs is a leading cause of morbidity and mortality worldwide. Hypoxia stimulates the secretion of vascular endothelial growth factor (VEGF) and other angiogenic factors, leading to neovascularization and protection against ischaemic injury. Here we show that the transcriptional coactivator PGC-1alpha (peroxisome-proliferator-activated receptor-gamma coactivator-1alpha), a potent metabolic sensor and regulator, is induced by a lack of nutrients and oxygen, and PGC-1alpha powerfully regulates VEGF expression and angiogenesis in cultured muscle cells and skeletal muscle in vivo. PGC-1alpha-/- mice show a striking failure to reconstitute blood flow in a normal manner to the limb after an ischaemic insult, whereas transgenic expression of PGC-1alpha in skeletal muscle is protective. Surprisingly, the induction of VEGF by PGC-1alpha does not involve the canonical hypoxia response pathway and hypoxia inducible factor (HIF). Instead, PGC-1alpha coactivates the orphan nuclear receptor ERR-alpha (oestrogen-related receptor-alpha) on conserved binding sites found in the promoter and in a cluster within the first intron of the VEGF gene. Thus, PGC-1alpha and ERR-alpha, major regulators of mitochondrial function in response to exercise and other stimuli, also control a novel angiogenic pathway that delivers needed oxygen and substrates. PGC-1alpha may provide a novel therapeutic target for treating ischaemic diseases.
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              Testosterone physiology in resistance exercise and training: the up-stream regulatory elements.

              Testosterone is one of the most potent naturally secreted androgenic-anabolic hormones, and its biological effects include promotion of muscle growth. In muscle, testosterone stimulates protein synthesis (anabolic effect) and inhibits protein degradation (anti-catabolic effect); combined, these effects account for the promotion of muscle hypertrophy by testosterone. These physiological signals from testosterone are modulated through the interaction of testosterone with the intracellular androgen receptor (AR). Testosterone is important for the desired adaptations to resistance exercise and training; in fact, testosterone is considered the major promoter of muscle growth and subsequent increase in muscle strength in response to resistance training in men. The acute endocrine response to a bout of heavy resistance exercise generally includes increased secretion of various catabolic (breakdown-related) and anabolic (growth-related) hormones including testosterone. The response of testosterone and AR to resistance exercise is largely determined by upper regulatory elements including the acute exercise programme variable domains, sex and age. In general, testosterone concentration is elevated directly following heavy resistance exercise in men. Findings on the testosterone response in women are equivocal with both increases and no changes observed in response to a bout of heavy resistance exercise. Age also significantly affects circulating testosterone concentrations. Until puberty, children do not experience an acute increase in testosterone from a bout of resistance exercise; after puberty some acute increases in testosterone from resistance exercise can be found in boys but not in girls. Aging beyond 35-40 years is associated with a 1-3% decline per year in circulating testosterone concentration in men; this decline eventually results in the condition known as andropause. Similarly, aging results in a reduced acute testosterone response to resistance exercise in men. In women, circulating testosterone concentration also gradually declines until menopause, after which a drastic reduction is found. In summary, testosterone is an important modulator of muscle mass in both men and women and acute increases in testosterone can be induced by resistance exercise. In general, the variables within the acute programme variable domains must be selected such that the resistance exercise session contains high volume and metabolic demand in order to induce an acute testosterone response.
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                Author and article information

                Journal
                Physiol Rep
                Physiol Rep
                physreports
                phy2
                Physiological Reports
                Wiley Periodicals, Inc.
                2051-817X
                June 2014
                11 June 2014
                : 2
                : 6
                : e12033
                Affiliations
                [1 ]Department of Sports Sciences, Japan Institute of Sports Sciences, 3‐15‐1 Nishigaoka, KitaTokyo, Japan
                [2 ]Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
                [3 ]Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7‐3‐1 Hongo, BunkyoTokyo, Japan
                Author notes
                CorrespondenceMichihiro Kon, Department of Sports Sciences, Japan Institute of Sports Sciences,3‐15‐1 Nishigaoka, Kita, Tokyo 115‐0056, Japan.Tel: +81‐3‐5963‐0234Fax: +81‐3‐5963‐0232E‐mail: kon.michihiro@ 123456gmail.com
                Article
                phy212033
                10.14814/phy2.12033
                4208656
                24907297
                73ca23c8-948c-4c82-af7a-7e2c17de3e2c
                © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 April 2014
                : 02 May 2014
                : 07 May 2014
                Categories
                Original Research

                capillarization,resistance exercise training,skeletal muscle,systemic hypoxia

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