Obesity is a multifactorial condition arising from complex interactions between genetic susceptibility, environmental exposures, and behavioural factors. Among the genetic contributors identified through genome-wide association studies, variants within the fat mass and obesity-associated (FTO) gene represent some of the most consistently replicated loci associated with body mass index, adiposity, and appetite regulation across populations. Experimental and observational evidence suggests that FTO variants may influence energy intake, food preference, and metabolic pathways through effects on hypothalamic signalling, adipocyte biology, and epigenetic regulation. These findings have stimulated interest in precision nutrition approaches that aim to tailor dietary strategies according to individual genetic profiles. This narrative review critically examines the role of FTO gene variants in polygenic obesity and evaluates the current evidence supporting gene-diet interactions relevant to personalized weight management. We synthesized data from mechanistic studies, observational cohorts, randomized controlled trials, and meta-analyses to assess whether dietary interventions, including macronutrient composition, mediterranean-style dietary patterns, and discretionary food intake, can meaningfully modify obesity risk in individuals carrying FTO risk alleles. While mechanistic plausibility and observational associations are well established, evidence from intervention studies indicates that genotype-specific responses are generally modest and context-dependent. Overall, current findings support the potential of precision nutrition as a complementary framework rather than a deterministic approach to obesity management. Further large-scale, long-term, and ethnically diverse intervention studies are required to clarify clinical utility and inform evidence-based implementation.
Sewwandi et al. (Thu,) studied this question.