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

Proc. Natl. Acad. Sci. U.S.A. 113, 14372-14377 (2016)
Verlagsversion Forschungsdaten DOI
Excessive 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Alcohol Consumption ; Fgf21 ; Human ; Mouse Model ; β-klotho; Genome-wide Association; Consumption; Disease; Activation; Dependence; Sweet; Liver; Heart; Mice
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Quellenangaben Band: 113, Heft: 50, Seiten: 14372-14377 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Verlagsort Washington
Begutachtungsstatus Peer reviewed