Metabolic Mechanisms of Exercise-Induced Cardiac Remodeling

Abstract

Exercise has a myriad of physiological benefits that derive in part from its ability to improve cardiometabolic health. The periodic metabolic stress imposed by regular exercise appears fundamental in driving cardiovascular tissue adaptation. However, different types, intensities, or durations of exercise elicit different levels of metabolic stress and may promote distinct types of tissue remodeling. In this review, we discuss how exercise affects cardiac structure and function and how exercise-induced changes in metabolism regulate cardiac adaptation. Current evidence suggests that exercise typically elicits an adaptive, beneficial form of cardiac remodeling that involves cardiomyocyte growth and proliferation; however, chronic levels of extreme exercise may increase the risk for pathological cardiac remodeling or sudden cardiac death. An emerging theme underpinning acute as well as chronic cardiac adaptations to exercise is metabolic periodicity, which appears important for regulating mitochondrial quality and function, for stimulating metabolism-mediated exercise gene programs and hypertrophic kinase activity, and for coordinating biosynthetic pathway activity. In addition, circulating metabolites liberated during exercise trigger physiological cardiac growth. Further understanding of how exercise-mediated changes in metabolism orchestrate cell signaling and gene expression could facilitate therapeutic strategies to maximize the benefits of exercise and improve cardiac health.

Mitochondria-associated lactate dehydrogenase is not a biologically significant contributor to bioenergetic function in murine striated muscle

“…The presence of LDH within mitochondria could be particularly important to the heart, which has high energetic requirements that further increase with exercise. The rationale for examining mLDH is strengthened by the fact that circulating lactate concentration correlates positively with myocardial lactate uptake and oxidation [3,18,19] and can contribute remarkably to cardiac ATP production in mammals [2]. Importantly, any NADH generated within mitochondria during the LDH reaction would be directly available to the respiratory chain, bypassing the need to transport reducing equivalents across the inner mitochondrial membrane via the malate-aspartate shuttle.…”

“…Results of our exercise capacity tests indicated that lactate abundance negatively correlated with running distance only in untrained mice, which suggests potential adaptations to circulating lactate. Because the heart strongly adapts to exercise [2], is a net lactate consumer [2], and is a primary contributor to exercise capacity [20], we tested whether exercise influences lactate-supported respiration in isolated heart mitochondria. In both cardiac and skeletal muscle mitochondria, lactate failed to support significant amounts of respiration.…”

“…Periods of heightened physical activity further increase the energy demands of the heart. During exercise, higher circulating levels of lactate provide the heart with increased levels of oxidizable substrate [1,2]. Although high blood lactate levels increase lactate oxidation and diminish myocardial glucose catabolism [[2], [3], [4]], the mechanisms by which lactate regulates cardiac energetics and function remain incompletely understood.…”

Exercise-Induced Regulation of Redox Status in Cardiovascular Diseases: The Role of Exercise Training and Detraining

“…Numerous epidemiological studies have convincingly demonstrated the beneficial effect of physical exercise on CVD outcomes, and thus, it has been considered as a valuable therapeutic approach for CVDs [56,[66][67][68][69]. The favorable effect of regular exercise on CVDs progress is primarily attributed on the exercise-mediated enhancement of the antioxidant capacity and reduction of oxidative stress levels that subsequently results in redox balance preservation and cellular homeostasis [63,64].…”

Energy Metabolism in Exercise-Induced Physiologic Cardiac Hypertrophy

“…In a study of myocardial gene expression profile in rats, it was shown that during exercise-induced physiological myocardial hypertrophy, the glucose signal of cardiomyocytes was significantly different, while there was no significant change in pathological hypertrophy ( Kong et al., 2005 ). A large number of studies have proved that the metabolic coordination is an essential condition for myocardial adaptive growth ( Turpeinen et al., 1996 ; Peterzan et al., 2017 ; Fulghum and Hill, 2018 ; Gibb and Hill, 2018 ; Heallen et al., 2020 ), but it is not clear whether the regulation of myocardial energy metabolism can reverse myocardial remodeling and improve myocardial function. Therefore, the study of energy metabolism in exercise-induced physiological cardiac hypertrophy is beneficial to the exploration of exercise-induced cardiac adaptation and might be a unique research perspective for interventions in heart failure and other cardiovascular diseases.…”