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Critical Reviews™ in Eukaryotic Gene Expression
Fator do impacto: 2.156 FI de cinco anos: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Imprimir: 1045-4403
ISSN On-line: 2162-6502

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Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v22.i4.60
pages 325-343

Monogenic and Complex Forms of Obesity: Insights from Genetics Reveal the Leptin-Melanocortin Signaling Pathway as a Common Player

Doreen Zegers
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
Wim Van Hul
Department of Medical Genetics, University of Antwerp (UA) and Department of Medical Genetics, University Hospital of Antwerp (UZA)
Luc F. Van Gaal
Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp
Sigri Beckers
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium


The role of genetic factors involved in the etiology of human obesity is beyond question. The identification of the hypothalamic leptin-melanocortin signaling pathway as a critical regulator in energy homeostasis and food intake has been essential for genetic research. In this review, we discuss the involvement of established and novel genes from this pathway in the pathogenesis of obesity. Their roles in monogenic and complex forms of obesity are illustrated by discussing the results of mutation analysis, candidate gene and genome-wide association studies, as well as copy number analysis. While we can conclude from these outcomes that the leptin-melanocortin pathway is of immense importance, there is still a lot of heritability that currently cannot be explained. Future studies implementing genome-wide association studies, genome-wide copy number variant analysis, and whole exome and whole-genome sequencing might aid in finding new variation in the conventional pathways and might reveal new biological pathways implicated in the pathogenesis of obesity.

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