Metabolomic Response throughout 16 Weeks of Combined Aerobic and Resistance Exercise Training in Older Women with Metabolic Syndrome

Abstract

Increases in longevity and obesity have led to a higher prevalence of Metabolic Syndrome (MetS) and several chronic conditions, such as hypertension. The prevalence of MetS and hypertension increases with advancing age and their detrimental effects on health can be attenuated by physical activity. Combined aerobic and resistance exercise training (CT) is recommended to maintain good health in older adults and is known to generate important metabolic adaptations. In this study we performed a metabolomics analysis, based on Hydrogen Nuclear Magnetic Resonance (1H NMR), to investigate the kinetics of changes in metabolism in non-physically active older women with MetS in response to 16 weeks of CT. A subset of women with MetS were selected from a larger randomized trial (that included men and women without MetS), with 12 participants on CT and 13 from the Control Group (CG). CT comprised walking/running at 63% of VO2max, three times/week, and resistance training (RT), consisting of 15 repetitions of seven exercises at moderate intensity, twice/week. Serum metabolomic profile was analysed at baseline (0W), 4 (4W), 8 (8W), 12 (12W) and 16 weeks (16W) for CT or CG. Cardiorespiratory fitness, RT load, blood pressure, body composition, lipid and glycaemic profile were also assessed. After 16 weeks CT increased cardiorespiratory fitness (13.1%, p < 0.05) and RT load (from 48% in the lat pulldown to 160% in the leg press, p < 0.05), but there were no changes in MetS parameters, such as body composition (Body Mass, Body Mass Index (BMI), body fat percentage and waist circumference), blood pressure, lipid and glycaemic profile. However, we identified potential higher substrate to the tricarboxylic acid cycle (increase in 2-Oxobutyrate from 0W (0.0029 ± 0.0009) to 4W (0.0038 ± 0.0011) and 8W (0.0041 ± 0.0015), p < 0.05), followed by alterations (different from 0W, p < 0.05) in the production of ketone bodies (3-Hydroxybutyrate, 0W (0.0717 ± 0.0377) to 16W (0.0397 ± 0.0331), and Acetoacetate, 0W (0.0441 ± 0.0240) to 16W (0.0239 ± 0.0141)), which together might explain the known improvement in fatty acid oxidation with exercise. There was also a late increase in ornithine at 16W of CT. Further studies are needed to investigate the association between these metabolic pathways and clinical outcomes in this population.

Keywords: aging; cardiovascular health; combined training; elderly; exercise; menopause; metabolism; metabolites; metabolomics; physical training.

Figure 1

Principal component analysis (PCA). Control Group (CG) is represented by the square (☐) and the Combined Training (CT) is represented by the circle (◯). Colours vary according to the time of data collection; 0W = green: pre-training; 4W = pink: 4 weeks; 8W = yellow: 8 weeks; 12W = red: 12 weeks; 16W = blue: 16 weeks. The present model used data for all 66 metabolites detected.

Figure 2

Partial least squares discriminant analysis (PLS-DA). Control Group (CG) is represented by the square (☐) and the Combined Training (CT) is represented by the circle (◯). Colours vary according to the time of data collection; 0W = green: baseline; 4W = pink: 4 weeks; 8W = yellow: after 8 weeks of training; 12W = red: after 12 weeks of training; 16W = blue: after 16 weeks of training. The present model used data for all 66 metabolites detected.