Weight Loss Increases Circadian Gene Expression and Emotional Well-Being in individuals with Obesity

Carmen Grau-del Valle¹Neus Bosch-Sierra¹Alberto Hermo-Argibay¹Sandra López-Domenech¹Milagros Rocha¹Victor M Victor²Carlos Morillas¹Susana Rovira-Llopis^1*Celia Bañuls^1*

• ¹Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
• ²Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain, Valencia, Spain

Introduction: Obesity is associated with disruptions in circadian rhythms and emotional well-being that can contribute to metabolic and psychological health issues. This study aimed to investigate the effects of weight loss by a dietary intervention on circadian gene expression and emotional state in individuals with obesity. Methods: 50 subjects with obesity followed a dietary intervention for 6 months. Anthropometric and biochemical parameters were assessed. Sleep quality was measured using a sleep questionnaire and Rosemberg Self-Esteem Scale, Beck Depression Inventory and State-Trait Anxiety Inventory (STAI) were used. PBMCs' RNA was analyzed for circadian-related gene expression. Results: Participants lost 11.3% body weight, along with reductions in lipid, carbohydrate metabolism and inflammation markers. Sleep quality improved; as poor sleep frequency was reduced, though sleep duration was similar. Self-esteem did not significantly increase; however, the proportion of participants with high self-esteem rose from 62% to 69% (χ²=12.5, p<0.05). State anxiety decreased (STAI-S, p<0.01), though trait anxiety remained stable. Several circadian genes were upregulated, including CLOCK, ARNTL, CRY1, DBP, and NR1D1; with associations found between CLOCK and lower state anxiety at baseline, and between CRY2 and higher self-esteem and lower depression at baseline (p<0.05). Conclusions: The dietary intervention influenced positively the metabolic, psychological, and circadian rhythm marker profile, highlighting potential interconnections between metabolism, circadian gene expression, and mental well-being.