Obesity: Underlying Mechanisms and the Evolving Influence of Diet

Abstract

Obesity is determined by both genetic and environmental factors. Since 2007, 52 genes have been associated with obesity and obesity-related measurements in genome-wide association studies (GWAS), among these the fat and obesity-associated gene (FTO). Despite the success in identifying genes predisposing to obesity, these GWAS hits only account for approximately about 5 % of the estimated obesity heritability and do not predict who will become obese and who will not. The missing heritability might be accounted for by gene-gene and gene-environment interactions. Most consistently, physical activity has been shown to attenuate the effect of FTO on obesity. Several studies have examined gene-diet interactions in relation to obesity, but only a few suggestive interactions have been identified. This is most probably due to small effect sizes of the interactions and thereby a demand for large samples sizes and accurate measurements of exposures and outcomes. In addition to SNPs, epigenetic changes have been suggested to account for some of the missing heritability, and epigenetic changes have been shown to be induced by dietary intake of mothers, in utero conditions, and early nutrition and can lead to increased risk of developing obesity. Recently, the intestinal microbiome, the collected genome of the bacteria, also has been associated with obesity and with specific dietary profiles. The underlying mechanisms determining the susceptibility to obesity do not only include the genome but also the epigenome and the microbiome that can be modified by diet, and by genotype, adding to the complexity of determining the contributors to obesity. © 2012 Springer Science+Business Media, LLC.