| Literature DB >> 27911795 |
Gunter Schumann1, Chunyu Liu2,3,4, Paul O'Reilly5, He Gao6,7, Parkyong Song8,9, Bing Xu5, Barbara Ruggeri5, Najaf Amin10, Tianye Jia5, Sarah Preis4, Marcelo Segura Lepe6,11, Shizuo Akira12, Caterina Barbieri13, Sebastian Baumeister14,15, Stephane Cauchi16, Toni-Kim Clarke17, Stefan Enroth18, Krista Fischer19, Jenni Hällfors20, Sarah E Harris21,22, Saskia Hieber23, Edith Hofer24,25, Jouke-Jan Hottenga26, Åsa Johansson18, Peter K Joshi27, Niina Kaartinen28, Jaana Laitinen29, Rozenn Lemaitre30, Anu Loukola20,31, Jian'an Luan32, Leo-Pekka Lyytikäinen33, Massimo Mangino34,35, Ani Manichaikul36,37, Hamdi Mbarek26, Yuri Milaneschi38, Alireza Moayyeri6,39,40, Kenneth Mukamal41, Christopher Nelson42,43, Jennifer Nettleton44, Eemil Partinen45, Rajesh Rawal46, Antonietta Robino47, Lynda Rose48, Cinzia Sala13, Takashi Satoh12, Reinhold Schmidt24, Katharina Schraut27, Robert Scott49, Albert Vernon Smith50, John M Starr21,51, Alexander Teumer14,52, Stella Trompet53,54, André G Uitterlinden55,56, Cristina Venturini34, Anne-Claire Vergnaud6, Niek Verweij57, Veronique Vitart58, Dragana Vuckovic59, Juho Wedenoja31, Loic Yengo16, Bing Yu60,61, Weihua Zhang6,62, Jing Hua Zhao49, Dorret I Boomsma26, John Chambers6,62,63, Daniel I Chasman48,64, Toniolo Daniela13, Eco de Geus26, Ian Deary21,65, Johan G Eriksson28,66,67,68,69, Tõnu Esko19, Volker Eulenburg70, Oscar H Franco56, Philippe Froguel16,71, Christian Gieger46, Hans J Grabe72, Vilmundur Gudnason50,73, Ulf Gyllensten18, Tamara B Harris74, Anna-Liisa Hartikainen75,76,77, Andrew C Heath78, Lynne Hocking79, Albert Hofman56, Cornelia Huth80, Marjo-Riitta Jarvelin6,77,81,82, J Wouter Jukema53, Jaakko Kaprio20,28,31, Jaspal S Kooner62,63,83, Zoltan Kutalik84, Jari Lahti68,85,86, Claudia Langenberg32, Terho Lehtimäki33, Yongmei Liu87, Pamela A F Madden88, Nicholas Martin89, Alanna Morrison60, Brenda Penninx38, Nicola Pirastu27,59, Bruce Psaty30,90,91,92, Olli Raitakari93,94, Paul Ridker48,64, Richard Rose95, Jerome I Rotter96, Nilesh J Samani42,43, Helena Schmidt97, Tim D Spector34, David Stott98, David Strachan99, Ioanna Tzoulaki6,7,100, Pim van der Harst57,101,102, Cornelia M van Duijn10, Pedro Marques-Vidal103, Peter Vollenweider103, Nicholas J Wareham49, John B Whitfield89, James Wilson27,58, Bruce Wolffenbuttel104, Georgy Bakalkin105, Evangelos Evangelou6,100, Yun Liu106,107, Kenneth M Rice108, Sylvane Desrivières5, Steven A Kliewer8,109, David J Mangelsdorf110,9, Christian P Müller23, Daniel Levy2,3, Paul Elliott111,7.
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.Entities:
Keywords: FGF21; alcohol consumption; human; mouse model; β-Klotho
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Year: 2016 PMID： 27911795 PMCID： PMC5167198 DOI： 10.1073/pnas.1611243113
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205