Identifying regulatory hubs in obesity with nutrigenomics

Purpose of review Deciphering the factors underlying the widespread obesity witnessed in Westernized societies has revealed the complexity of this polygenic metabolic disease. Indeed, the interactions between lifestyle (physical activity, smoking, diet, etc.) and an individual's genetic make-up suggest that many people are genetically susceptible to gaining weight. Thus, a nutritional genomics approach is a natural evolution in our attempt to unravel the complex interactions between diet, genes and obesity. Recent findings The emerging notion that the molecular network underlying a given physiological state comprises critical regulatory enzymes (alternatively referred to as hubs or nexuses) suggests that while many genes may be sensitive to changes in adiposity, only a subset of these will be highly influential in defining the obese phenotype. As exemplified by transcription factors (PPARγ, LXRα, etc.) and stearoyl-coenzyme desaturase (SCD1), these hubs have dominant roles within the adipogenic regulatory network; however, identifying such hubs is not trivial. One attractive method involves integrating microarray technology with the up-and-coming promise of comprehensive metabolite profiling. Summary Integrating comprehensive profiling platforms remains an ambitious endeavor; however, such a holistic approach has the means to accelerate our understanding of how diet and genes interact to influence the obese phenotype.