Evidence for Epigenetic Changes as a Cause of Clinical Obesity

Abstract

There is substantial evidence from epidemiology and from animal models that risk of obesity and its related conditions is modified by the quality of the early life environment, in particular, nutrition, behavior, and exposure to hormones. Such exposures represent signals which act through developmental plasticity to induce variation in the phenotype of the offspring. Induction of alternative phenotypes during development in response to environmental cues is consistent with a number of examples from nature in which, under appropriate conditions, the induced phenotype is adaptive. Recent studies in animal models and in humans show that induction of an altered phenotype during early life by social and nutritional stressors involves altered epigenetic regulation of specific non-imprinted genes by DNA methylation and histone modifications. Induced changes in DNA methylation involve alteration of a few specific CpG dinucleotides within the promoter region and are associated with changes in the mRNA expression and activity of DNA methyltransferases. There are some encouraging recent findings which show that for at least some early life exposures induction of an altered phenotype and epigenotype can be prevented or modified by nutritional interventions. Together these findings suggest the possibility of novel epigenetic biomarkers and therapeutic interventions to reduce the risk for obesity in later life.