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

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

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systematic review

Abstract

Aim

The obesity epidemic has been largely attributed to changes in lifestyle habits established over the past three decades. These changes are mainly attributed to excessive nutrition and decline in physical activity as well as additional factors such as reduced intestinal microbiota diversity, sleep duration, endocrine disruptors, and reduced variability of the ambient temperature. However, the obesogenic environment is not sufficient to determine the presence of obesity, it is necessary that the lifestyle becomes associated with a personal predisposition for the phenotype to emerge. In this article, we review the main forms of monogenic and syndromic obesity, as well as a historical summary of the search for the genes that add up to confer greater risk for the development of polygenic obesity.

Methods

We carried out a PubMed search, along with ExcerptaMedica database (EMBASE)/Cochrane library, Web Sciences for the Medical Subject Headings (MeSH) terms “obesity’’ AND “genetics” for the past 5-years.

Results

We found a total of 14057 articles pertaining to obesity and genetics together of which we selected 92 articles for this review after getting articles after searching cross references.

Conclusion

Studies with twins and adopted children show that 55 to 80% of the variation of body mass index (BMI) is attributed to genetic factors. According to the genetic criteria, obesity can be classified as A) Monogenic – when a mutated gene is responsible for the phenotype; B) Syndromic – when a set of specific symptoms are present and a small group of genes is involved; usually the term is used to describe obese patients with cognitive delay, dysmorphic features, organ-specific abnormalities, hyperphagia, and/or other signs of hypothalamic dysfunction; C) Polygenic – also called “common” obesity, present in up to 95% of cases. Many genes add up to give a greater risk to the individual, and if associated with some habits culminates in obesity. In spite of its great relevance, the search for the genes that raise the risk of obesity has not been easy. It is still a challenge for the scientific community to separate the genetic element from the environmental component in the etiology of this disease. Individuals more susceptible to excessive adiposity may carry risk variants in the genes that influence appetite control, the regulation of cellular machinery, lipid metabolism and adipogenesis, the energy expenditure, insulin signaling, and inflammation.

Keywords

Obesity; Genetics; Polygenic; Monogenic; Syndromic; Polymorphism.