The Interplay of Genetic Predisposition, Circadian Misalignment, and Metabolic Regulation in Obesity

This review explores the complex interplay between genetic predispositions to obesity, circadian rhythms, metabolic regulation, and sleep. It highlights how genetic factors underlying obesity exacerbate metabolic dysfunction through circadian misalignment and examines promising interventions to mitigate these effects.

Genome-wide association Studies (GWAS) have identified numerous Single Nucleotide Polymorphisms (SNPs) associated with obesity traits, attributing 40-75% heritability to body mass index (BMI). These findings illuminate critical links between genetic obesity, circadian clocks, and metabolic processes. SNPs in clock-related genes influence metabolic pathways, with disruptions in circadian rhythms-driven by poor sleep hygiene or erratic eating patterns-amplifying metabolic dysfunction. Circadian clocks, synchronized with the 24-h light-dark cycle, regulate key metabolic activities, including glucose metabolism, lipid storage, and energy utilization. Genetic mutations or external disruptions, such as irregular sleep or eating habits, can destabilize circadian rhythms, promoting weight gain and metabolic disorders. Circadian misalignment in individuals with genetic predispositions to obesity disrupts the release of key metabolic hormones, such as leptin and insulin, impairing hunger regulation and fat storage. Interventions like time-restricted feeding (TRF) and structured physical activity offer promising strategies to restore circadian harmony, improve metabolic health, and mitigate obesity-related risks.