Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome

Takashi Yokota, Shintaro Kinugawa, Kagami Hirabayashi, Tadashi Suga, Shingo Takada, Masashi Omokawa, Tomoyasu Kadoguchi, Masashige Takahashi, Arata Fukushima, Shouji Matsushima, Mayumi Yamato, Koichi Okita, Hiroyuki Tsutsui

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Aims/Introduction: Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). Here, we investigated the effects of pioglitazone treatment on whole-body aerobic capacity and skeletal muscle energy metabolism in MetS patients. Materials and Methods: A total of 14 male patients with MetS received oral pioglitazone 15 mg/day for 4 months. To assess whole-body aerobic capacity, exercise testing with a bicycle ergometer was carried out before and after pioglitazone treatment. To assess skeletal muscle energy metabolism, intramyocellular lipid in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus magnetic resonance spectroscopy, respectively. Results: Pioglitazone significantly increased peak oxygen uptake (25.1 ± 4.9 mL/kg/min pretreatment vs 27.2 ± 3.9 mL/kg/min post- treatment, P < 0.05) and anaerobic threshold (12.7 ± 1.9 mL/kg/min pretreatment vs 13.6 ± 1.6 mL/kg/min post-treatment, P < 0.05), although daily physical activity was comparable before and after the treatment. Intramyocellular lipid content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased the muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in anaerobic threshold; that is, submaximal aerobic capacity, closely correlated with the decrease in intramyocellular lipid content after pioglitazone treatment. Conclusions: Pioglitazone significantly improved the MetS patients’ whole-body aerobic capacity and skeletal muscle energy metabolism. The beneficial effect of pioglitazone on whole-body aerobic capacity might be at least in part through improved fatty acid metabolism in the skeletal muscle.

    Original languageEnglish
    Pages (from-to)535-541
    Number of pages7
    JournalJournal of Diabetes Investigation
    Volume8
    Issue number4
    DOIs
    Publication statusPublished - Jul 2017

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    pioglitazone
    Energy Metabolism
    Skeletal Muscle
    Exercise
    Anaerobic Threshold
    Lipids
    Therapeutics
    Fatty Acids
    Phosphates
    Muscles
    Phosphocreatine

    All Science Journal Classification (ASJC) codes

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome. / Yokota, Takashi; Kinugawa, Shintaro; Hirabayashi, Kagami; Suga, Tadashi; Takada, Shingo; Omokawa, Masashi; Kadoguchi, Tomoyasu; Takahashi, Masashige; Fukushima, Arata; Matsushima, Shouji; Yamato, Mayumi; Okita, Koichi; Tsutsui, Hiroyuki.

    In: Journal of Diabetes Investigation, Vol. 8, No. 4, 07.2017, p. 535-541.

    Research output: Contribution to journalArticle

    Yokota, T, Kinugawa, S, Hirabayashi, K, Suga, T, Takada, S, Omokawa, M, Kadoguchi, T, Takahashi, M, Fukushima, A, Matsushima, S, Yamato, M, Okita, K & Tsutsui, H 2017, 'Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome', Journal of Diabetes Investigation, vol. 8, no. 4, pp. 535-541. https://doi.org/10.1111/jdi.12606
    Yokota, Takashi ; Kinugawa, Shintaro ; Hirabayashi, Kagami ; Suga, Tadashi ; Takada, Shingo ; Omokawa, Masashi ; Kadoguchi, Tomoyasu ; Takahashi, Masashige ; Fukushima, Arata ; Matsushima, Shouji ; Yamato, Mayumi ; Okita, Koichi ; Tsutsui, Hiroyuki. / Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome. In: Journal of Diabetes Investigation. 2017 ; Vol. 8, No. 4. pp. 535-541.
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    abstract = "Aims/Introduction: Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). Here, we investigated the effects of pioglitazone treatment on whole-body aerobic capacity and skeletal muscle energy metabolism in MetS patients. Materials and Methods: A total of 14 male patients with MetS received oral pioglitazone 15 mg/day for 4 months. To assess whole-body aerobic capacity, exercise testing with a bicycle ergometer was carried out before and after pioglitazone treatment. To assess skeletal muscle energy metabolism, intramyocellular lipid in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus magnetic resonance spectroscopy, respectively. Results: Pioglitazone significantly increased peak oxygen uptake (25.1 ± 4.9 mL/kg/min pretreatment vs 27.2 ± 3.9 mL/kg/min post- treatment, P < 0.05) and anaerobic threshold (12.7 ± 1.9 mL/kg/min pretreatment vs 13.6 ± 1.6 mL/kg/min post-treatment, P < 0.05), although daily physical activity was comparable before and after the treatment. Intramyocellular lipid content was significantly reduced after pioglitazone treatment by 26{\%}, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased the muscle phosphocreatine loss during exercise by 13{\%}, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in anaerobic threshold; that is, submaximal aerobic capacity, closely correlated with the decrease in intramyocellular lipid content after pioglitazone treatment. Conclusions: Pioglitazone significantly improved the MetS patients’ whole-body aerobic capacity and skeletal muscle energy metabolism. The beneficial effect of pioglitazone on whole-body aerobic capacity might be at least in part through improved fatty acid metabolism in the skeletal muscle.",
    author = "Takashi Yokota and Shintaro Kinugawa and Kagami Hirabayashi and Tadashi Suga and Shingo Takada and Masashi Omokawa and Tomoyasu Kadoguchi and Masashige Takahashi and Arata Fukushima and Shouji Matsushima and Mayumi Yamato and Koichi Okita and Hiroyuki Tsutsui",
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    T1 - Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome

    AU - Yokota, Takashi

    AU - Kinugawa, Shintaro

    AU - Hirabayashi, Kagami

    AU - Suga, Tadashi

    AU - Takada, Shingo

    AU - Omokawa, Masashi

    AU - Kadoguchi, Tomoyasu

    AU - Takahashi, Masashige

    AU - Fukushima, Arata

    AU - Matsushima, Shouji

    AU - Yamato, Mayumi

    AU - Okita, Koichi

    AU - Tsutsui, Hiroyuki

    PY - 2017/7

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    N2 - Aims/Introduction: Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). Here, we investigated the effects of pioglitazone treatment on whole-body aerobic capacity and skeletal muscle energy metabolism in MetS patients. Materials and Methods: A total of 14 male patients with MetS received oral pioglitazone 15 mg/day for 4 months. To assess whole-body aerobic capacity, exercise testing with a bicycle ergometer was carried out before and after pioglitazone treatment. To assess skeletal muscle energy metabolism, intramyocellular lipid in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus magnetic resonance spectroscopy, respectively. Results: Pioglitazone significantly increased peak oxygen uptake (25.1 ± 4.9 mL/kg/min pretreatment vs 27.2 ± 3.9 mL/kg/min post- treatment, P < 0.05) and anaerobic threshold (12.7 ± 1.9 mL/kg/min pretreatment vs 13.6 ± 1.6 mL/kg/min post-treatment, P < 0.05), although daily physical activity was comparable before and after the treatment. Intramyocellular lipid content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased the muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in anaerobic threshold; that is, submaximal aerobic capacity, closely correlated with the decrease in intramyocellular lipid content after pioglitazone treatment. Conclusions: Pioglitazone significantly improved the MetS patients’ whole-body aerobic capacity and skeletal muscle energy metabolism. The beneficial effect of pioglitazone on whole-body aerobic capacity might be at least in part through improved fatty acid metabolism in the skeletal muscle.

    AB - Aims/Introduction: Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). Here, we investigated the effects of pioglitazone treatment on whole-body aerobic capacity and skeletal muscle energy metabolism in MetS patients. Materials and Methods: A total of 14 male patients with MetS received oral pioglitazone 15 mg/day for 4 months. To assess whole-body aerobic capacity, exercise testing with a bicycle ergometer was carried out before and after pioglitazone treatment. To assess skeletal muscle energy metabolism, intramyocellular lipid in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus magnetic resonance spectroscopy, respectively. Results: Pioglitazone significantly increased peak oxygen uptake (25.1 ± 4.9 mL/kg/min pretreatment vs 27.2 ± 3.9 mL/kg/min post- treatment, P < 0.05) and anaerobic threshold (12.7 ± 1.9 mL/kg/min pretreatment vs 13.6 ± 1.6 mL/kg/min post-treatment, P < 0.05), although daily physical activity was comparable before and after the treatment. Intramyocellular lipid content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased the muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in anaerobic threshold; that is, submaximal aerobic capacity, closely correlated with the decrease in intramyocellular lipid content after pioglitazone treatment. Conclusions: Pioglitazone significantly improved the MetS patients’ whole-body aerobic capacity and skeletal muscle energy metabolism. The beneficial effect of pioglitazone on whole-body aerobic capacity might be at least in part through improved fatty acid metabolism in the skeletal muscle.

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