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Gene & Protein in Disease Genetic pleiotropy in birth weight and fat

from overweight or obesity (data collected in 33 countries the time of birth. 13,14 The developmental origins of health
and nearly 411,000 children aged 6 – 9 evaluated). Data and disease theory 15-17 link birth weight to obesity risk
1-4
analyzed by the World Obesity Federation suggests a further through fetal adaptations to adverse conditions, but it does
surge in the prevalence of overweight and obesity, with an not fully explain the association with metabolic issues.
estimation of 206 million global cases among children and Indeed, normal variation in size at birth seems to be
adolescents by 2025, and up to 254 million by 2030. 1-4 influenced not only by the maternal uterine environment
Although obesity primarily stems from an imbalance but also by the interactions between it and the fetal genetic
18
between energy intake and expenditure, recent research factors. Thus, although the link between birth weight and
over the past years has highlighted the role of various other adult body mass index remains unclear, some genomic
contributing factors, including fetal growth and birth alterations are thought to influence both fetal growth and
weight. 5-8 post-natal body mass. 19

2. Birth weight and childhood obesity Specifically, potential involvement of gene variants
and epigenetic modifications associated with both birth
Inadequate birth weight has been associated with risk weight and adipose tissue regulation could be proposed,
of obesity and cardiometabolic disease in adulthood if suggesting that a genetic pleiotropy may modify growth
obesity develops at a young age. Both high and low birth efficiency during the fetal stage, contributing to the
9
weights influence obesity risk and related health issues, development of diseases later in life and serving as a link
forming a U-shaped pattern (Figure 1). Lower birth between birth weight and obesity. 20
weight, in particular, is associated with increased visceral In this context, genetic and epigenetic signals affecting
fat and a higher likelihood of cardiometabolic diseases like the insulin-like growth factor 1 (IGF1)/insulin axis,
10
type 2 diabetes in adulthood. Conversely, higher birth insulin-like growth factor 2 (IGF2), and peroxisome
weight is associated with elevated body mass index in both proliferator-activated receptors (PPARs) may be highly
childhood and adulthood. 11,12 relevant, as they play a dual role in fetal growth and
Birth weight serves as a reflection of the intrauterine adipocyte differentiation. IGF1 and IGF2 are key regulators
environment, making it an important indicator of health at of cell growth, differentiation, and metabolism. Their

Figure 1. U-shaped relationship between birth weight and risk of obesity and related health issues. Both low and high birth weights are associated with
increased risk, highlighting the link between prenatal development and future metabolic health. Image created by the author.

Volume 4 Issue 3 (2025) 2 doi: 10.36922/GPD025070011