Fiche publication
Date publication
juillet 2025
Journal
Metabolism: clinical and experimental
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MEYRE David
Tous les auteurs :
El Kouche S, Meyre D
Lien Pubmed
Résumé
The "thrifty genotype hypothesis" states that gene variants promoting efficient fat deposition may have been advantaged by natural selection to allow human survival during famine. Nowadays, such genes are rendered detrimental by progress as they promote fat deposition in preparation for a famine that never comes, resulting in widespread obesity. Obesity is genetically heterogeneous, with a continuum between very rare syndromic, rare monogenic, and common polygenic forms of obesity. The identification of natural selection signatures has been largely restricted to polygenic obesity-susceptibility variants, and this approach has failed to validate the thrifty genotype hypothesis. However, polygenic variants may not be as relevant as monogenic mutations, characterized by strong phenotypic effects on body mass index variation and obesity risk, in detecting significant signatures of natural selection.
Mots clés
Genomic constraints, Monogenic obesity, Multiethnic population, Mutation intolerance, Natural selection, Syndromic obesity, Thrifty genotype hypothesis
Référence
Metabolism. 2025 07 23;:156353
