Adipose gene expression prior to weight loss can differentiate and weakly predict dietary responders
Résumé
Background.The ability to identify obese individuals who will successfully lose weight in response to dietary intervention willrevolutionize disease management. Therefore, we asked whether it is possible to identify subjects who will lose weight duringdietary intervention using only a single gene expression snapshot.Methodology/Principal Findings.The present studyinvolved 54 female subjects from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary Guidelines(NUGENOB) trial to determine whether subcutaneous adipose tissue gene expression could be used to predict weight loss priorto the 10-week consumption of a low-fat hypocaloric diet. Using several statistical tests revealed that the gene expressionprofiles of responders (8–12 kgs weight loss) could always be differentiated from non-responders (,4 kgs weight loss). Wealso assessed whether this differentiation was sufficient for prediction. Using a bottom-up (i.e. black-box) approach, standardclass prediction algorithms were able to predict dietary responders with up to 61.1%68.1% accuracy. Using a top-downapproach (i.e. using differentially expressed genes to build a classifier) improved prediction accuracy to 80.9%62.2%.Conclusion.Adipose gene expression profiling prior to the consumption of a low-fat diet is able to differentiate respondersfrom non-responders as well as serve as a weak predictor of subjects destined to lose weight. While the degree of predictionaccuracy currently achieved with a gene expression snapshot is perhaps insufficient for clinical use, this work reveals that thecomprehensive molecular signature of adipose tissue paves the way for the future of personalized nutrition.