The genetics of childhood obesity and interaction with dietary macronutrients

Abstract

The genes contributing to childhood obesity are categorized into three different types based on distinct genetic and phenotypic characteristics. These types of childhood obesity are represented by rare monogenic forms of syndromic or non-syndromic childhood obesity, and common polygenic childhood obesity. In some cases, genetic susceptibility to these forms of childhood obesity may result from different variations of the same gene. Although the prevalence for rare monogenic forms of childhood obesity has not increased in recent times, the prevalence of common childhood obesity has increased in the United States and developing countries throughout the world during the past few decades. A number of recent genome-wide association studies and mouse model studies have established the identification of susceptibility genes contributing to common childhood obesity. Accumulating evidence suggests that this type of childhood obesity represents a complex metabolic disease resulting from an interaction with environmental factors, including dietary macronutrients. The objective of this article is to provide a review on the origins, mechanisms, and health consequences of obesity susceptibility genes and interaction with dietary macronutrients that predispose to childhood obesity. It is proposed that increased knowledge of these obesity susceptibility genes and interaction with dietary macronutrients will provide valuable insight for individual, family, and community preventative lifestyle intervention, and eventually targeted nutritional and medicinal therapies.

Pediatric obesity. An introduction

“…Obesity is also just as clearly a genetic disease, because all available data suggest that 60–80% of the observed variance in human body weight can be accounted for by inherited factors (Wardle, Carnell, Haworth, & Plomin, 2008). Finally, there is good evidence for gene × environment interactions for obesity risk alleles (Ahmad et al, 2011; Andreasen et al, 2008; Demerath et al, 2013; Garver et al, 2013; Qi et al, 2012; Rampersaud et al, 2008; Rosenquist et al, 2015). Thus, for obesity, “genetic background loads the gun, but the environment pulls the trigger” (Bray, 2004).…”

Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype

“…Although “caloric imbalance”, is an important contributor to obesity 1 , it is abundantly clear that maternal nutrition is a major intrauterine environmental factor for the expression of the fetal genome, with lifelong consequences on the health of the offspring, including the development of obesity and metabolic syndrome 2 . This phenomenon, termed “fetal programming” and the consequent “fetal origins of adult diseases” has been well-described in offspring following intrauterine growth restriction (IUGR) 3-5 , but the underlying cellular/molecular link between the two remains unknown.…”

Individual Genetic Variations Related to Satiety and Appetite Control Increase Risk of Obesity in Preschool-Age Children in the STRONG Kids Program

“…There is a need to replicate findings from GWAS using a systems biology approach with markers located in or nearby genes involved in regulatory hypothalamic pathways (BDNF, FTO, LEPR, MC4R, and POMC) and to evaluate if other genetic associations identified in this network (LEP, PCSK1, and TUB) could strengthen our understanding of obesity risk in preschoolers [23] . LEP and PCSK1 are among the susceptibility genes responsible for nonsyndromic childhood obesity and participate in the integration of peripheral and neuronal signals through the leptin-melanocortin hypothalamic pathway and are also responsible for maintaining energy balance through food consumption and energy expenditure [22] .…”