Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson's Disease Patients

Abstract

Regular exercise ameliorates motor symptoms in Parkinson's disease (PD). Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals (n = 11/11). The effects of exercise on resting energy expenditure (REE), glucose metabolism, adiposity, and muscle energy metabolism (31P-MRS) were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS), bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK). However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr) recovery (31P-MRS) were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF) expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of Sirt1 and Cox7a1, and the parameters of fitness/strength were positively associated with the expression of MyHC2, MyHC7, and MGF. Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; 31P-MRS). Exercise training improved the clinical state in early/mid-stage Parkinson's disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise-induced improvements in the PD clinical state were associated with specific adaptive changes in muscle functional, metabolic, and molecular characteristics.

Clinical trial registration: www.ClinicalTrials.gov, identifier NCT02253732.

Keywords: 31P-MRS; Parkinson’s disease; energy metabolism; exercise training; muscle metabolism.

Figures

Figure 1

Effects of a 3-month combined endurance/strength training on the clinical state of the PD patients [MDS-UPDRS, (A,B)], including bradykinesia (C), balance (D), dynamic motor functions (E), and walking speed on a 1-mile track (F). Data are expressed as average ± SEM, *p < 0.05, †p < 0.1.

Figure 2

Exercise intervention-induced changes in muscle mass (A), strength (B), and VO2max (C). The muscle of PD patients exhibited type IIb fiber hypertrophy (D,E,F) and a proportion of type II fibers was associated with resting energy expenditure (REE), [(D)-insert], cross-sectional microscopic image of skeletal muscle (m. vastus lateralis) from a healthy senior (E) and a PD patient (F); Time constant for muscle postexercise phosphocreatine (PCr) recovery (τPCr) was positively associated with the bradykinesia disability score (G), time in the walking test (H), and with 2-h glycemia (I). Data are expressed as average ± SEM, *p < 0.05, †p < 0.1; MVC, maximal voluntary contraction force. Type I, IIa, and IIb muscle fibers are identified by different ATPase staining intensity.

Figure 3

Effects of a 3-month combined endurance/strength training on fasting glycemia (A), glycemic curve [oral glucose tolerance test, (B)], and REE (C). REE was associated with muscle mass in the entire study population (D). Data are expressed as average ± SEM, *p < 0.05, †p < 0.1; REE, resting energy expenditure; LBM, lean body mass; PD, Parkinson’s disease.

Figure 4

Associations of (i) clinical PD disability score (MDS-UPDRS), (ii) whole-body and muscle metabolism (resting energy expenditure, FPG, 2HG, Qmax), (iii) functional, and (vi) morphological characteristics with the expression of genes related to muscle functional phenotypes, energy metabolism, and mitochondrial biogenesis. ATP2A1, sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform (Serca1); BDNF, brain-derived neurotrophic factor; Cpt 1, carnitine palmitoyltransferase 1; Cox7a1, cytochrome c oxidase polypeptide 7a1 isoform; FNDC5, fibronectin type III domain containing 5- precursor of Irisin; FoxJ3, forkhead box J3; MGF, mechano-growth factor—splice variant of the Insulin-Like Growth Factor-1 (IGF-1 Ec); MDS-UPDRS, Movement Disorder Society–Unified Parkinson’s Disease Rating Scale, MyHC, myosin heavy chain isoform; NCAM 1, neural cell adhesion molecule 1 isoform; ND1, NADH dehydrogenase subunit 1 was measured to determine the amount of mitochondrial DNA relative to the expression of genomic DNA for Rpl13a; PRKAA1, AMP-activated protein kinase alpha catalytic subunit 1 (AMPKα1); Qmax, dynamic muscle ATP flux; SLN, sarcolipin; Sirt, sirtuin; VEGF, vascular endothelial growth factor; VO2max, maximal aerobic capacity.