Genetic variation in the hypothalamic pathways and its role on obesity

Authors

  • J. V. Van Vliet-Ostaptchouk,

    Corresponding author
    1. Molecular Genetics, Medical Biology Section, Department of Pathology and Medical Biology, University Medical Center and University of Groningen, Groningen;
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  • M. H. Hofker,

    1. Molecular Genetics, Medical Biology Section, Department of Pathology and Medical Biology, University Medical Center and University of Groningen, Groningen;
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  • Y. T. Van Der Schouw,

    1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht;
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  • C. Wijmenga,

    1. Department of Genetics, University Medical Center and University of Groningen, Groningen, the Netherlands;
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  • N. C. Onland-Moret

    1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht;
    2. Complex Genetics Section, Department of Medical Genetics, University Medical Center Utrecht
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JV van Vliet-Ostaptchouk, Molecular Genetics (HPC EA12), Department Pathology and Medical Biology, University Medical Center Groningen, Building 3215, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands. E-mail: j.v.van.vliet@med.umcg.nl

Summary

Over recent decades, the prevalence of obesity has increased dramatically worldwide. Although this epidemic is mainly attributable to modern (western) lifestyle, multiple twin and adoption studies indicate the significant role of genes in the individual's predisposition to becoming obese. As the hypothalamus plays a central role in controlling body weight, its regulatory circuits may represent a crucial system in the pathogenesis of the disorder. Genetic variations in genes in the hypothalamic pathways may therefore contribute to the susceptibility for obesity in humans and animals.

We summarize current knowledge on the physiological role of the hypothalamus in body-weight regulation and review genetic studies on the hypothalamic candidate genes in relation to obesity. Together, data from functional and genetic studies as well as the new, common, obesity loci identified in genome-wide association scans support an important role for the hypothalamic genes in predisposing to obesity. However, findings are still inconclusive for many candidate genes. To improve our understanding of the genetic architecture of common obesity, we suggest that specific obesity phenotypes should be considered and different analytical approaches used. Such studies should consider multiple genes from the same physiological pathways, together with environmental risk factors.

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