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A comprehensive review of genetic causes of obesity

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Abstract

Background

Obesity is a multifactorial chronic disease with a high, increasing worldwide prevalence. Genetic causes account for 7% of the cases in children with extreme obesity.

Data sources

This narrative review was conducted by searching for papers published in the PubMed/MEDLINE, Embase and SciELO databases and included 161 articles. The search used the following search terms: “obesity”, “obesity and genetics”, “leptin”, “Prader-Willi syndrome”, and “melanocortins”. The types of studies included were systematic reviews, clinical trials, prospective cohort studies, cross-sectional and prospective studies, narrative reviews, and case reports.

Results

The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight. However, several important aspects of the pathophysiology of obesity remain unknown. Genetic causes of obesity can be grouped into syndromic, monogenic, and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years, hyperphagia, or a family history of extreme obesity. A microarray study, an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose. There are three therapeutic levels: lifestyle modifications, pharmacological treatment, and bariatric surgery.

Conclusions

Genetic study technologies are in constant development; however, we are still far from having a personalized approach to genetic causes of obesity. A significant proportion of the affected individuals are associated with genetic causes; however, there are still barriers to its approach, as it continues to be underdiagnosed.

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Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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Authors and Affiliations

  1. Universidad Científica del Sur, Bolivar 2150 Avenue, Pueblo Libre, 15084, Lima, Peru

    Marcio José Concepción-Zavaleta

  2. Division of Medicine, Hospital de Apoyo Chepén, Chepén, Peru

    Juan Eduardo Quiroz-Aldave

  3. Division of Family Medicine, Hospital de Apoyo Chepén, Chepén, Peru

    María del Carmen Durand-Vásquez

  4. Division of Endocrinology, Hospital Víctor Lazarte Echegaray, Trujillo, Peru

    Elman Rolando Gamarra-Osorio

  5. Division of Pediatrics, Hospital de Apoyo Chepén, Chepén, Peru

    Juan del Carmen Valencia de la Cruz & Claudia Mercedes Barrueto-Callirgos

  6. Division of Internal Medicine, Hospital de Apoyo Chepén, Chepén, Peru

    Susan Luciana Puelles-León

  7. Division of Genetics, Universidad Nacional de Trujillo, Trujillo, Peru

    Elena de Jesús Alvarado-León & Frans Leiva-Cabrera

  8. Division of Neonatology, Hospital Belén de Trujillo, Trujillo, Peru

    Francisca Elena Zavaleta-Gutiérrez

  9. Division of Internal Medicine, Universidad Nacional de Trujillo, Trujillo, Peru

    Luis Alberto Concepción-Urteaga

  10. Department of Medicine, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru

    José Paz-Ibarra

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  1. Marcio José Concepción-Zavaleta
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Contributions

CZMJ contributed to conceptualization, methodology, reviewing and editing, and project administration. QAJE contributed to conceptualization, methodology, investigation, writing of the original draft, and project administration. DVMdC, VdlCJdC, BCCM, and PLSL contributed to investigation and writing of the original draft. GOER contributed to investigation, reviewing and editing. ALEdJ, LCF, ZGFE, and CULA contributed to reviewing and editing. PIJ contributed to conceptualization, methodology, reviewing and editing. All authors approve the final version of the manuscript.

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Correspondence to Marcio José Concepción-Zavaleta.

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Concepción-Zavaleta, M.J., Quiroz-Aldave, J.E., Durand-Vásquez, M.d. et al. A comprehensive review of genetic causes of obesity. World J Pediatr 20, 26–39 (2024). https://doi.org/10.1007/s12519-023-00757-z

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