Epigenetic programming of obesity in early life through modulation of the kynurenine pathway.

Abstract

Childhood obesity is a global health concern that has its origins before birth. Although genetics plays a crucial role, increasing evidence suggests that epigenetic modifications during fetal life could also influence its incidence. In this model, during the fetal period, interactions between genetic makeup, intrauterine factors, and environmental conditions, increase the risk of childhood obesity. This is in accordance with the Developmental Origins of Health and Disease (DOHaD) hypothesis, in which specific intrauterine environments can have long-lasting effects on the immune system's essential functions during crucial stages of fetal growth, resulting in permanent changes to the immune function of the offspring. Consequently, dysfunction can consequently make the offspring more prone to inflammatory and immune-related disorders later in life. In this review, we examine how maternal inflammation could influence the risk of childhood obesity. We propose that during pregnancy, modification of the expression of critical genes in metabolic and signaling pathways, such as the kynurenine (Kyn) pathway, occurs due to increased levels of maternal inflammation. We also propose that such expression differences are mediated by epigenetic changes. Furthermore, we also hypothesize that the Kyn pathway produces metabolites that have immunoregulatory effects and may play a crucial role in regulating inflammation during pregnancy. As a result, interventions aimed at improving maternal inflammation may be able to help alleviate the risk of childhood obesity.