Enantioselectivity of Isomerization of n-Humulone to trans- and cis-n-Isohumulones.

Circadian rhythms regulate a broad range of physiological processes, including energy metabolism, hormone secretion, sleep–wake cycles, and exercise performance (; ; ; ). Increasing evidence suggests that exercise is not only an effective lifestyle strategy for improving metabolic health but also a non-photic zeitgeber capable of modulating peripheral circadian clocks. Consequently, the timing of exercise may influence metabolic responses to training as well as the effectiveness of fat-loss interventions, making exercise timing an important topic in both circadian biology and exercise science (; ; ; ; ). However, current evidence regarding the effects of exercising at different times of day on weight-loss outcomes remains inconsistent (). In a randomized controlled trial involving 88 overweight and obese young adults, Willis et al. found that participants assigned to morning exercise achieved significantly greater reductions in body weight and fat mass over 10 months than those assigned to afternoon exercise (). Other studies, however, have reported different results. Savikj et al. showed that afternoon high-intensity interval exercise was more effective than morning exercise in lowering blood glucose levels in patients with type 2 diabetes (). Arciero et al. reported that morning exercise was particularly beneficial for reducing abdominal fat, whereas evening exercise was more effective in improving muscle performance in women (). In addition, Creasy et al. and Mancilla et al. found that afternoon or evening exercise may offer certain advantages for weight loss, fat reduction, and metabolic improvement (; ). Taken together, these inconsistent findings suggest that the effects of exercise timing may be moderated by individual differences rather than determined by a single “optimal” time for all individuals (; ). In addition to inter-individual variability, differences in exercise intensity and training modality may also contribute to the heterogeneous findings reported in the literature, as the time of day most favorable for exercise may depend on the physiological demands of the exercise performed (). For example, higher-intensity exercise may be more advantageous in the afternoon or evening, whereas lower-intensity exercise may be better tolerated or more effective in the morning (; ). It is therefore important to investigate exercise timing from the perspective of both individual variability and exercise characteristics. Genetic factors, particularly polymorphisms in circadian rhythm-related genes, may represent one of the key mechanisms underlying these differences (; ). Several circadian clock genes, including CLOCK, ARNTL/BMAL1, CRY, and PER family genes, have been implicated in chronotype- and sleep-related phenotypes. Among these candidate genes, PER3 (period circadian regulator 3) has been extensively studied in relation to chronotype, sleep timing, and behavioral rhythmicity. Previous studies suggest that PER3 polymorphisms may influence an individual’s adaptation to circadian disruption and may thereby contribute to variation in metabolic phenotypes and behavioral rhythm patterns (; ; ). The rs228697 polymorphism is a common variant within the PER3 gene and has been reported to be associated with chronotype tendency, with the G allele more frequently linked to evening preference and the C allele to morning preference (; ; ). Although this association has not been entirely consistent across studies, it nevertheless supports the use of this variant as a candidate marker for exploring the relationship between genetic circadian traits and exercise timing. Given the exploratory nature of the present study and the limited sample size, we focused on this prespecified candidate locus rather than examining a broader panel of circadian gene variants. Although an increasing number of studies have examined the effects of exercise performed at different times of day on weight control and body composition, their findings remain inconsistent (). Moreover, most previous studies have focused on average group-level effects and have paid limited attention to inter-individual differences in circadian traits and genetic background. Research examining whether PER3 polymorphisms modulate weight-loss responses to exercise performed at different times of day remains scarce, particularly intervention studies integrating genotype, behavioral rhythmicity, and exercise timing. This gap has limited the development of personalized exercise-timing strategies for precision weight management. Against this background, the present study focused on the PER3 rs228697 polymorphism and developed an exploratory genotype–exercise timing matching model to deliver an 8-week moderate-intensity continuous training (MICT) intervention in overweight and obese university students. MICT was chosen because it is a practical and commonly recommended exercise modality for weight management, is generally well tolerated in overweight populations, and