The Role of Genetics in the Pathophysiology of Obesity: A Systematic Review

Renata M. Pinto*, Lucas S. Steinmetz, Julio M. G. Barbosa, Arthur F. C. S. Mendes, Maria P. Curado and Aparecido D. da Cruz

The Role of Genetics in the Pathophysiology of Obesity: A Systematic Review.

In 2007, Speakman12 published the “predator release theory”, complementary to the “thrifty genotype” hypothesis. Based on anthropological and epidemiological evidence, genetic tracing and experimental research, the theory postulates that the higher agility characteristic of lean individuals has selected them who are better adapted for food search and escape from predators.

Genetic predisposition is an essential component in the genesis of obesity. Rare cases of monogenic and syndromic obesity have a well-established genetic background, and this knowledge has
contributed to revealing important molecular mechanisms in the pathophysiology of obesity. The diagnosis of these forms of obesity is important because it allows genetic counseling and, in some
cases, guides the treatment in a more specific way, as in Prader Willi Syndrome and leptin/melanocortin pathway mutations.

The polygenic nature of common obesity makes the discovery of risk genes and their variants a challenging task. GWAS studies have brought new insights to the understanding of the genesis of obesity. However, the contribution of specific genes to the phenotype of polygenic obesity still accounts for only a small part of BMI variability. Recently the development of GPS has proven
to be a valid risk score to identify individuals at higher risk for developing obesity, but still without a place in clinical practice.
The FTO is related, in addition to BMI, to the risk of obesity, abdominal circumference, body fat percentage and with childhood obesity. The second wave corroborated the association of obesity with FTO variations and identified a locus related to the MC4R.

Obes Res Open J. 2019; 6(1): 11-17. doi: 10.17140/OROJ-6-137