Interplay between diet, exercise and the molecular circadian clock in orchestrating metabolic adaptations of adipose tissue

Disruption of circadian rhythmicity induced by prolonged light exposure, altered sleep patterns and shift work is associated with the development of obesity and related metabolic disorders, including type 2 diabetes and cardiovascular diseases. White and brown adipose tissue activity shows circadian rhythmicity, with daily variations in the regulation of metabolic processes such as lipolysis, glucose and lipid uptake, and adipokine secretion. The role of the circadian clock in the regulation of energy homeostasis has raised interest in clock-related strategies to mitigate metabolic disturbances associated with type 2 diabetes, including 'resynchronizing' metabolism through diet or targeting a particular time of a day to potentiate the effect of a pharmacological or physiological treatment. Exercise is an effective intervention to prevent insulin resistance and type 2 diabetes. Beyond its effect on skeletal muscle, exercise training also has a profound effect on adipose tissue. Adipose tissue partly mediates the beneficial effect of exercise on glucose and energy homeostasis, via its metabolic and endocrine function. The interaction between zeitgeber time and diet or exercise is likely to influence the metabolic response of adipose tissue and therefore impact the whole-body phenotype. Understanding the impact of circadian clock systems on human physiology and how this is regulated by exercise in a tissue-specific manner will yield new insights for the management of metabolic disorders.