title: FGF21 Regulates Sweet and Alcohol Preference.
abstract: Fibroblast growth factor 21 (FGF21) is a hormone induced by various metabolic stresses, including ketogenic and high-carbohydrate diets, that regulates energy homeostasis. In humans, SNPs in and around the FGF21 gene have been associated with macronutrient preference, including carbohydrate, fat, and protein intake. Here we show that FGF21 administration markedly reduces sweet and alcohol preference in mice and sweet preference in cynomolgus monkeys. In mice, these effects require the FGF21 co-receptor β-Klotho in the central nervous system and correlate with reductions in dopamine concentrations in the nucleus accumbens. Since analogs of FGF21 are currently undergoing clinical evaluation for the treatment of obesity and type 2 diabetes, our findings raise the possibility that FGF21 administration could affect nutrient preference and other reward behaviors in humans.
authors.affiliation: Cardiovascular and Metabolic Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.
authors.forename: Saswata
authors.initials: S
authors.lastname: Talukdar
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Bryn M
authors.initials: BM
authors.lastname: Owen
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Parkyong
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Genaro
authors.initials: G
authors.lastname: Hernandez
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cardiovascular and Metabolic Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.
authors.forename: Yingjiang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Scott
authors.affiliation: Drug Safety Research and Development, Pfizer Worldwide Research and Development, Groton, CT 06340, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Paratala
authors.affiliation: Cardiovascular and Metabolic Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.
authors.forename: Tod
authors.initials: T
authors.lastname: Turner
authors.affiliation: Drug Safety Research and Development, Pfizer Worldwide Research and Development, Groton, CT 06340, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.affiliation: Drug Safety Research and Development, Pfizer Worldwide Research and Development, Groton, CT 06340, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bernardo
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany; MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Müller
authors.affiliation: Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: davo.mango@utsouthwestern.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.affiliation: Cardiovascular and Metabolic Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Goodwin
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: steven.kliewer@utsouthwestern.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kliewer
mesh_terms: D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005518:Food Preferences / Q000187:drug effects*; D000882:Haplorhini; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D012439:Saccharin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013649:Taste / Q000187:drug effects*
chemical_list: D000438:Alcohols; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D012439:Saccharin; D004298:Dopamine