2. Academic Validation
  3. FGF21 Regulates Sweet and Alcohol Preference

FGF21 Regulates Sweet and Alcohol Preference

  • Cell Metab. 2016 Feb 9;23(2):344-9. doi: 10.1016/j.cmet.2015.12.008.
Saswata Talukdar 1,  Bryn M Owen 2,  Parkyong Song 2,  Genaro Hernandez 2,  Yuan Zhang 2,  Yingjiang Zhou 1,  William T Scott 2,  Bhavna Paratala 3,  Tod Turner 1,  Andrew Smith 3,  Barbara Bernardo 3,  Christian P Müller 4,  Hao Tang 5,  David J Mangelsdorf 6,  Bryan Goodwin 1,  Steven A Kliewer 7
Affiliations

Affiliations

  • 1 Cardiovascular and Metabolic Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.
  • 2 Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 3 Drug Safety Research and Development, Pfizer Worldwide Research and Development, Groton, CT 06340, USA.
  • 4 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.
  • 5 Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 6 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.
  • 7 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.
PMID: 26724861 DOI: 10.1016/j.cmet.2015.12.008
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.

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