KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference

Article, Other literature type, Other ORP type, Unknown English OPEN
Schumann, Gunter ; Liu, Chunyu ; O’Reilly, Paul ; Gao, He ; Song, Parkyong ; Xu, Bing ; Ruggeri, Barbara ; Amin, Najaf ; Jia, Tianye ; Preis, Sarah ; Segura Lepe, Marcelo ; Akira, Shizuo ; Barbieri, Caterina ; Baumeister, Sebastian ; Cauchi, Stephane ; Clarke, Toni-Kim ; Enroth, Stefan ; Fischer, Krista ; Hällfors, Jenni ; Harris, Sarah E. ; Hieber, Saskia ; Hofer, Edith ; Hottenga, Jouke-Jan ; Johansson, Åsa ; Joshi, Peter K. ; Kaartinen, Niina ; Laitinen, Jaana ; Lemaitre, Rozenn ; Loukola, Anu ; Luan, Jian’an ... view all 127 authors (2016)
  • Publisher: National Academy of Sciences
  • Journal: volume 113, issue 50, pages 14,372-14,377 (issn: 0027-8424, eissn: 1091-6490)
  • Related identifiers: doi: 10.1073/pnas.1611243113, doi: 10.17863/CAM.7898
  • Subject: MD Multidisciplinary | mouse model | ?-Klotho | β-Klotho | FGF21 | alcohol consumption | human | Biological Sciences

textabstractExcessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among > 105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10-12). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
  • References (26)
    26 references, page 1 of 3

    1. Anonymous (2014) Global Status Report on Alcohol and Health (WHO, Geneva).

    2. Rehm J, et al. (2009) Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373(9682):2223-2233.

    3. Rose G (1981) Strategy of prevention: Lessons from cardiovascular disease. Br Med J (Clin Res Ed) 282(6279):1847-1851.

    4. Hines LM, Rimm EB (2001) Moderate alcohol consumption and coronary heart disease: A review. Postgrad Med J 77(914):747-752.

    5. Heath AC, Meyer J, Eaves LJ, Martin NG (1991) The inheritance of alcohol consumption patterns in a general population twin sample. I. Multidimensional scaling of quantity/frequency data. J Stud Alcohol 52(4):345-352.

    6. Bierut LJ, et al. (2012) ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry. Mol Psychiatry 17(4):445-450.

    7. Schumann G, et al. (2011) Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proc Natl Acad Sci USA 108(17):7119-7124.

    8. Fisher FM, Maratos-Flier E (2016) Understanding the physiology of FGF21. Annu Rev Physiol 78:223-241.

    9. Owen BM, Mangelsdorf DJ, Kliewer SA (2015) Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol Metab 26(1):22-29.

    10. Dushay JR, et al. (2014) Fructose ingestion acutely stimulates circulating FGF21 levels in humans. Mol Metab 4(1):51-57.

  • Similar Research Results (1)
  • Metrics
    No metrics available
Share - Bookmark