Abstract : Obesity represents a major health concern, not just in the West but increasingly in low and middle income countries. In order to develop successful strategies for losing weight, it is essential to understand the molecular pathogenesis of weight change. A number of pathways, implicating oxidative stress but also the fundamental regulatory of insulin, have been implicated in weight gain and in the regulation of energy expenditure. In addition, a considerable body of work has highlighted the role of metabolites generated by the gut microbiome, in particular short chain fatty acids, in both processes. The current review provides a brief understanding of the mechanisms underlying the associations of weight change with changes in lipid and amino acid metabolism, energy metabolism, dietary composition and insulin dynamics, as well as the influence of the gut microbiome. The changes in metabolomic profiles and the models outlined can be used as an accurate predictor for obesity and obesity related disorders.