Association between dietary intake and the expression of clock genes in adults: a brief report

Marlene Lages^1,2,3,4,5Renata Barros^2,3,4Marisa Ferreira-Marques^6,7,8Joana Correia⁵Armando Caseiro^5,9Maria Pedro Guarino^1,10Sara Carmo-Silva^1,5,9*

• ¹Center for Innovative Care and Health Technology, Polytechnic Institute of Leiria, Leiria, Portugal
• ²Faculty of Nutrition and Food Science, University of Porto, Porto, Portugal
• ³Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, Porto, Portugal
• ⁴EPIUnit – Institute of Public Health, University of Porto, Porto, Portugal
• ⁵Coimbra Health School, Polytechnic University of Coimbra, Coimbra, Portugal
• ⁶CNC-UC – Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
• ⁷CIBB – Center for Innovation in Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
• ⁸Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
• ⁹H&TRC – Health and Technology Research Center, Coimbra Health School, Polytechnic University of Coimbra, Coimbra, Portugal
• ¹⁰ESSLei, School of Health Sciences, Polytechnic University of Leiria, Leiria, Portugal

Background: The circadian system regulates several physiological processes, including energy metabolism, through the expression of core clock genes. Animal studies suggest that dietary composition can influence circadian gene expression; however, evidence in humans remains limited. Objective: Explore the association between dietary macronutrient intake and the expression of circadian clock genes in whole blood of adults with distinct metabolic profiles. Methods: Nineteen adults (94.7% female; 43.4 ± 16.05 years) were categorized into healthy-weight and overweight/obesity groups based on BMI. Dietary intake was assessed using a three-day food diary, and clock gene expression (CLOCK, BMAL1, PER2, CRY) was evaluated in whole blood samples collected at 08:00 AM and 04:00 PM. Statistical analyses included group comparisons and correlation analyses between macronutrient intake and gene expression. Results: No statistically significant differences were observed in clock gene expression between BMI groups, although group-level trends were noted, particularly in PER2 and CRY expression. The overweight/obesity group exhibited a significantly higher percentage of energy intake from protein. Correlation analyses revealed several time-dependent associations between macronutrient intake and clock gene expression. Notably, in the healthy BMI group, BMAL1 and CRY expression correlated with lipid and protein intake, while in the overweight/obesity group, CLOCK expression was strongly associated with both lipid and carbohydrate intake. Conclusion: These findings suggest that macronutrient composition may influence peripheral circadian gene expression in a time-and BMI-dependent manner. Further research is necessary to confirm these associations in larger and more diverse populations and to investigate the potential of chrononutrition strategies to support metabolic health.