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

J Diabetes Investig. 2017 Jul;8(4):535-541. doi: 10.1111/jdi.12606. Epub 2017 Jan 31.

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 1 proton- and 31 phosphorus 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.

Keywords: Clinical; Metabolic syndrome; Treatment drug.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Energy Metabolism / drug effects*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Lipid Metabolism / drug effects
  • Male
  • Metabolic Syndrome / drug therapy*
  • Middle Aged
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Oxidative Stress / drug effects
  • Phosphates / metabolism
  • Pioglitazone
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*

Substances

  • Hypoglycemic Agents
  • Phosphates
  • Thiazolidinediones
  • Pioglitazone