Exercise provides health benefits to multiple metabolic tissues through complex biological pathways and interactions between organs. However, investigating these complex mechanisms in humans is still limited, making mouse models extremely useful for exploring exercise-induced changes in whole-body metabolism and health. In this review, we focus on gaining a broader understanding of the metabolic phenotypes and molecular mechanisms induced by exercise in mouse models. We first discuss the differences in adaptations induced by aerobic and resistance exercise, and compare voluntary wheel running and forced treadmill exercise, the two main methods of aerobic exercise research in mice, to show the similarities and differences between the same aerobic exercise but different methods, and their impact on experimental outcomes. The effects of exercise on metabolic phenotypes, including alleviation of obesity and metabolic disorders, and the mechanisms involved in adipose tissue remodelling and browning are explored, as well as the role of the gut microbiota in mediating the physiological responses and metabolic effects of exercise. Understanding these molecular mechanisms and methodological aspects of exercise experiments in mouse models can serve as a valuable template for the design of future basic research in exercise physiology and will provide a strong scientific evidence base for optimizing the design of exercise intervention programmes for metabolic health.
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