The scale of the problem is enormous. According to data cited in the review from the World Health Organization, in 2022 approximately 2.5 billion adults were living with overweight, including more than 890 million adults with obesity. Projections suggest that by 2030 these numbers could rise to more than 2.9 billion adults with overweight and roughly 1.2 billion with obesity. The economic burden is equally staggering, with global costs associated with overweight and obesity expected to increase from approximately US$2 trillion in 2020 to more than US$3 trillion by 2030, potentially exceeding US$18 trillion by 2060. Beyond the numbers, obesity imposes a considerable clinical burden through its association with chronic low-grade inflammation, insulin resistance, type 2 diabetes, cardiovascular disease, and obstructive sleep apnea.

Sleep and circadian biology have assumed a central role in contemporary discussions of obesity etiology. Epidemiological and experimental evidence demonstrates that short sleep duration, poor sleep quality, irregular sleep-wake schedules, and circadian misalignment are associated with increased risk of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. The circadian timing system influences energy metabolism, appetite, glycemic homeostasis, hormone secretion, and eating behavior, thereby contributing to the development and maintenance of excess weight. Obstructive sleep apnea, highly prevalent in people with obesity, is associated with intermittent hypoxia, sleep fragmentation, oxidative stress, systemic inflammation, and sympathetic hyperactivity, all of which exacerbate the adverse metabolic effects of excess adiposity.

Physical exercise has emerged as a strategy capable of simultaneously acting on several of these interconnected mechanisms. In addition to its well-established effects on body composition, energy expenditure, and cardiorespiratory fitness, regular exercise may improve sleep quality, facilitate circadian synchronization, reduce inflammatory and oxidative stress markers, and promote beneficial autonomic and metabolic adaptations. The review emphasizes that exercise can act as a non-photic zeitgeber, influencing peripheral clocks, clock-gene expression, body temperature, hormonal rhythms, and metabolic responses, while conversely, circadian phase and individual chronotype may influence exercise performance and physiological responses.

At the molecular level, circadian rhythms are generated by a highly conserved transcriptional-translational feedback loop comprising core clock genes. The transcription factors CLOCK and BMAL1 form a heterodimer that activates the expression of Period and Cryptochrome genes, whose protein products subsequently inhibit CLOCK:BMAL1 activity, generating self-sustained oscillations with an approximately 24-hour periodicity. Clock genes regulate the rhythmic expression of numerous downstream genes involved in glucose metabolism, insulin signaling, lipid metabolism, mitochondrial function, and energy homeostasis. Alterations in clock gene expression or function have been associated with circadian disruption and increased risk of metabolic disorders, including obesity and type 2 diabetes. Exercise can modulate the expression of these clock genes, particularly in skeletal muscle, where an intrinsic circadian system temporally regulates metabolic pathways and cellular function.

The review highlights the emerging concept of chronoexercise, which suggests that the effects of exercise on metabolic health depend not only on its intensity, duration, and frequency but also on the time of day it is performed. Glucose tolerance, insulin sensitivity, and beta-cell responsiveness are generally higher in the morning and progressively decline throughout the day. Several studies have reported that exercise performed in the late afternoon or early evening is associated with greater improvements in glycemic control, insulin sensitivity, and lipid metabolism compared with morning exercise, particularly in individuals with overweight, obesity, or type 2 diabetes. Conversely, morning exercise may provide specific metabolic advantages, such as increased fat oxidation during fasted conditions. However, current evidence does not support a universally optimal time of day for exercise, and individual circadian characteristics, habitual exercise timing, and the alignment between training and performance should be considered when evaluating time-of-day effects.

Regarding neuroendocrine regulation, obesity can alter food-intake signaling, particularly through leptin resistance, which is commonly observed in individuals with obesity. Exercise can modulate appetite through physiological mechanisms that influence eating behavior and gastric motility and reduce hunger signals. Chronic exercise appears to reduce appetite and food intake and increase energy expenditure, potentially through mechanisms involving greater anorexigenic activity. Distinct effects on neuropeptides involved in food intake and satiety have been observed according to the acute or chronic effects of exercise, with longitudinal interventions in adolescents with obesity showing significant reductions in leptin and melanin-concentrating hormone. A recent meta-analysis demonstrated that individuals with overweight or obesity who engaged in regular exercise experienced reductions in body weight and body mass index, although across most studies ghrelin concentrations were increased or unchanged.

Exercise also promotes the conversion of white adipose tissue into beige adipose tissue through a process known as browning, which may contribute to increased energy expenditure. In obesity, metabolic alterations in white adipose tissue, primarily driven by adipocyte hypertrophy and hypoxia, promote adipose tissue dysfunction and increased secretion of pro-inflammatory mediators, including interleukin-6, tumor necrosis factor-alpha, and leptin, accompanied by reductions in anti-inflammatory markers such as adiponectin. Regular exercise can reduce pro-inflammatory biomarkers in obesity, and a meta-analysis reported that combined aerobic and resistance training was the most beneficial exercise modality for improving inflammatory markers and body composition in individuals with overweight or obesity compared with isolated aerobic exercise, resistance training, or high-intensity interval training.

The influence of exercise on sleep architecture is another critical dimension. One of the most consistent findings is an increase in slow-wave sleep, with meta-analytic evidence indicating that exercise significantly increases this restorative sleep stage. The effects on rapid eye movement sleep are less consistent, showing a tendency toward reduction, particularly in both acute and chronic intervention protocols. Exercise-induced thermoregulation may play a central role, as the elevation in body temperature during exercise may interact with the physiological decline in core body temperature that occurs during the evening and early night, a process important for sleep initiation. Sessions performed between 4 and 8 hours before bedtime appear more effective at increasing slow-wave sleep, while those conducted too close to bedtime may be detrimental. Beyond improving body composition and cardiovascular responses, exercise modulates the autonomic nervous system by increasing parasympathetic activity and reducing excessive sympathetic activity, with heart rate variability serving as a non-invasive marker of cardiac autonomic modulation that may represent a potential physiological link between exercise and sleep.

In the context of sleep-related breathing disorders, exercise has emerged as a promising non-pharmacological strategy to improve autonomic regulation through mechanisms that extend beyond weight loss alone. A randomized controlled trial implemented a six-month supervised concurrent exercise program consisting of moderate-intensity aerobic and resistance training performed three times per week, significantly improving metaboreflex control and attenuating exaggerated sympathetic responses in patients with obstructive sleep apnea. Another mechanism involves body fluid dynamics, as gravitational forces during prolonged sitting promote fluid accumulation in the lower limbs, which upon assuming the supine position during sleep is redistributed toward the neck, increasing peripharyngeal tissue volume and upper airway collapsibility. One week of moderate-intensity walking increased daily physical activity by approximately 80 percent, reduced overnight rostral fluid shift by 40 percent, and attenuated the reduction in pharyngeal air volume during sleep, adaptations accompanied by a 30 percent reduction in the apnea-hypopnea index without changes in body weight.

The review also addresses behavioral and psychological dimensions, noting that excess adiposity induces significant neurobiological alterations that modify brain circuits involved in regulating mood and eating behavior. Conversely, depressive and anxiety disorders may contribute to weight gain through hormonal alterations, reduced physical activity, changes in eating behavior, and impaired sleep quality, establishing a reciprocal and self-perpetuating relationship. Chronotype and social jetlag, reflecting individual differences in preferred timing and misalignment between biological and socially imposed schedules, have been associated with obesity and adverse metabolic outcomes. Evening chronotypes have also been associated with lower levels of physical activity and greater sedentary behavior, suggesting that circadian preferences may influence engagement in regular exercise.

Despite the growing consistency of evidence supporting beneficial effects of exercise on sleep, circadian rhythms, mental health, and metabolic regulation, important knowledge gaps remain. Questions regarding the most effective exercise modality, intensity, duration, frequency, and particularly the timing of exercise remain incompletely answered. Accumulating evidence suggests there is unlikely to be a single optimal exercise prescription applicable to all individuals, with considerable interindividual variability in physiological and clinical responses influenced by intrinsic factors including age, sex, chronotype, genetic background, baseline physical fitness, and metabolic status, and extrinsic factors such as exercise timing, modality, intensity, sleep habits, dietary patterns, medication use, and environmental influences.

Individuals with obesity frequently face individual, social, and environmental barriers to initiating and maintaining a training routine, including obesity-related comorbidities, low motivation, difficulties with adherence, pain and physical discomfort, fatigue, lack of time, and limited social support. Environmental barriers such as limited access to suitable facilities, neighborhood insecurity, and lack of professional guidance can also reduce exercise levels in this population. Conversely, improvements in physical fitness, physical and mental wellbeing, and perceived pleasure during exercise have been associated with higher levels of physical activity, while resilience and realistic expectations regarding outcomes may also contribute to greater engagement.

The review concludes that physical exercise represents a key non-pharmacological strategy for the prevention and management of obesity, with benefits extending to metabolic health, sleep, and circadian regulation. Its effects depend not only on exercise type, intensity, and duration but may also be influenced by exercise timing and individual characteristics, including chronotype, sleep patterns, social jetlag, metabolic status, and behavioral context. The concept of chronoexercise expands the traditional approach to exercise prescription by incorporating its temporal dimension and interactions with other important circadian synchronizers, such as the light-dark cycle and meal timing. Although longitudinal studies and clinical trials are still needed to establish causal relationships and define more precise timing strategies, integrating exercise, sleep, and circadian biology offers a promising framework for more individualized interventions that may improve adherence and maximize sustainable benefits for the prevention and management of obesity and its associated metabolic and sleep disturbances.

Subject of Research: Health & Medicine

Article Title: Physical exercise as a modulator of the sleep–obesity interaction: metabolic, neuroendocrine and circadian mechanisms

Article References: Campos, R. M. S., de Sá Souza, H., Favaron, C. M., Saborosa, G. P., Ferez, L. C., Tufik, S., Antunes, H. K. M., D'Almeida, V., & Mônico-Neto, M. (2026). Physical exercise as a modulator of the sleep–obesity interaction: metabolic, neuroendocrine and circadian mechanisms. Frontiers in Sleep, 5, Article 1943600. https://doi.org/10.3389/frsle.2026.1943600

Image Credits: AI Generated

DOI: 10.3389/frsle.2026.1943600

Keywords: obesity, sleep, circadian rhythms, physical exercise, chronoexercise, metabolism, neuroendocrine, inflammation, sleep apnea, Frontiers in Sleep, Physical, exercise