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(2016)
KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.
Proceedings of the National Academy of Sciences of the United States of America (PNAS) ISSN 1091-6490, 113 (50).
pp. 14372-14377.
ISSN 1091-6490
https://doi.org/10.1073/pnas.1611243113
SGUL Authors: Strachan, David Peter
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Abstract
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.
| Item Type: | Article | ||||||||
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| Additional Information: | © 2016 National Academy of Sciences. | ||||||||
| Keywords: | FGF21, alcohol consumption, human, mouse model, β-Klotho, MD Multidisciplinary | ||||||||
| SGUL Research Institute / Research Centre: | Academic Structure > Population Health Research Institute (INPH) | ||||||||
| Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America (PNAS) ISSN 1091-6490 | ||||||||
| ISSN: | 1091-6490 | ||||||||
| Language: | eng | ||||||||
| Dates: |
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| Publisher License: | Publisher's own licence | ||||||||
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| PubMed ID: | 27911795 | ||||||||
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| URI: | https://openaccess.sgul.ac.uk/id/eprint/108394 | ||||||||
| Publisher's version: | https://doi.org/10.1073/pnas.1611243113 |
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