Genetics, epigenetics and transgenerational transmission of obesity in children

Abstract

Sedentary lifestyle and consumption of high-calorie foods have caused a relentless increase of overweight and obesity prevalence at all ages. Its presently epidemic proportion is disquieting due to the tight relationship of obesity with metabolic syndrome and several other comorbidities which do call for urgent workarounds. The usual ineffectiveness of present therapies and failure of prevention campaigns triggered overtime a number of research studies which have unveiled some relevant aspects of obesity genetic and epigenetic inheritable profiles. These findings are revealing extremely precious mainly to serve as a likely extra arrow to allow the clinician's bow to achieve still hitherto unmet preventive goals. Evidence now exists that maternal obesity/overnutrition during pregnancy and lactation convincingly appears associated with several disorders in the offspring independently of the transmission of a purely genetic predisposition. Even the pre-conception direct exposure of either father or mother gametes to environmental factors can reprogram the epigenetic architecture of cells. Such phenomena lie behind the transfer of the obesity susceptibility to future generations through a mechanism of epigenetic inheritance. Moreover, a growing number of studies suggests that several environmental factors such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during pregnancy and the early postnatal period may play critical roles in programming childhood adipose tissue and obesity. A deeper understanding of how inherited genetics and epigenetics may generate an obesogenic environment at pediatric age might strengthen our knowledge about pathogenetic mechanisms and improve the clinical management of patients. Therefore, in this narrative review, we attempt to provide a general overview of the contribution of heritable genetic and epigenetic patterns to the obesity susceptibility in children, placing a particular emphasis on the mother-child dyad.

Keywords: epigenetics; genetics; gestation; methylation; obesity; polymorphisms; pregnancy; transgenerational transmission.

Figure 1

Transgenerational epigenetic inheritance of obesity. When genetic background and lifestyle exposure cause epigenetic modifications (DNA methylation, histone modifications, and changes in non-coding RNAs) in gametes of a woman or a man at F0, the first generation that exhibits a transgenerational epigenetic inheritance is the F2. lncRNA, long non coding RNA; ncRNA, non coding RNA; miRNA, micro RNA. Figure partially created with BioRender.com.

Figure 2

In utero and postnatal predisposition to obesity. (A) During pregnancy, the placenta of a woman exposed to nutrition deficiency, overnutrition or obesogens, is subjected to inflammation, oxidative/nitrosative stress, lipid accumulation and insulin resistance that increases the risk of obesity and its comorbidities in the newborn. (B) The same risk of obesity and comorbidities early in the life could be associated to epigenetic changes occurring in the breast milk. Figure partially created with BioRender.com.