Genetics of childhood obesity

Genetics of Childhood Obesity: A Comprehensive Approach

Childhood obesity is a global health problem that has reached alarming levels, especially in countries such as Mexico, which ranks first in prevalence of childhood obesity worldwide. This article explores the genetic and environmental factors that contribute to the development of obesity in children, highlighting the importance of understanding genetic predisposition for the design of preventive and therapeutic interventions.

Background and Contributing Factors

In Mexico, almost eight out of ten adults are overweight or obese, and this trend extends to the child population. According to the 2012 National Health and Nutrition Survey (ENSANUT 2012), the combined prevalence of overweight and obesity in school-aged children is 34.4%, representing more than 5.6 million children. Obesity is a multifactorial condition, influenced by both environmental and genetic factors. While environmental factors include a high-calorie diet and sedentary lifestyle, not all individuals in the same environment develop obesity, underscoring the importance of genetic factors.

Genetics of Obesity

The genetic predisposition to obesity can be classified into three forms: monogenic, syndromic, and common. The monogenic form involves mutations in a single gene, such as the leptin gene or its receptor, while the syndromic form is associated with chromosomal abnormalities that often present with mental retardation, as in Prader-Willi syndrome. Common obesity is multifactorial and results from the interaction between multiple genes and environmental factors.

Genetics have been shown to contribute significantly to the development of obesity. Twin studies have shown that the heritability of the obesity phenotype can be as high as 70% in men and 66% in women. Several genes associated with obesity have been identified, including the adiponectin gene, adrenergic receptors, leptin and its receptor, the glucocorticoid receptor, and mitochondrial uncoupling proteins.

Genetic Polymorphisms and Obesity

Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with obesity and its comorbidities in the Mexican child population. The most studied genes include FTO, MC4R, TMEM18, GNPDA2, among others. For example, the FTO gene, first identified in relation to type 2 diabetes, has been shown to have a significant impact on body mass index (BMI). These findings suggest that certain SNPs may predispose to obesity by influencing factors such as appetite, energy expenditure, and fat storage.

Impact of Genetics on the Mexican Population

The Mexican population presents a unique genetic mix of Amerindian, European, and African ancestry. This genetic diversity may influence the predisposition to obesity and its complications. Recent studies have shown that specific genetic variants, such as the TCF7L2 gene, may confer protection or increase the risk of obesity in this population.

Metabolic Consequences of Childhood Obesity

Childhood obesity is associated with several metabolic complications, such as insulin resistance, dyslipidemia, and hypertension. Up to 25% of obese children in Mexico City have been found to have elevated glucose levels after meals, and 4% have undiagnosed type 2 diabetes. In addition, children with a family history of gestational or type 2 diabetes are at increased risk of developing early metabolic disorders.

Metabolic syndrome, a combination of factors such as hypertension, dyslipidemia, hyperinsulinemia, and central obesity, is common among obese children. The syndrome presents with chronic low-grade inflammation, characterized by elevated levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which contribute to insulin resistance.

Cytokines and Inflammatory Profile

Inflammation plays a crucial role in the development of obesity and its comorbidities. Proinflammatory cytokines such as IL-6 and TNF-α, largely produced by adipose tissue, contribute to insulin resistance. In contrast, adiponectin, an anti-inflammatory cytokine, improves insulin sensitivity and its decrease is associated with obesity, insulin resistance, and an atherogenic lipid profile.

Genetic Strategies for Obesity Management

Understanding the genetic contribution to obesity can guide the development of personalized prevention and treatment strategies. Identification of genetic biomarkers can be used predictively to identify individuals at risk before they develop the disease. Furthermore, genetic research can help develop targeted therapies that address specific metabolic pathways affected by particular genetic variants.

Conclusions

Childhood obesity is a complex condition influenced by genetic and environmental factors. Advances in genetics have made it possible to identify multiple genetic variants that contribute to obesity, providing a basis for future research that could lead to more effective interventions. In Mexico, it is crucial to conduct high-density genetic studies to identify specific markers in the population and improve knowledge about the molecular and physiological mechanisms that lead to this condition.

It is essential to promote the interaction between genetics and the environment in research on childhood obesity, in order to design preventive strategies that address risk factors from an early age and promote a better quality of life for future generations.