title: A low-protein diet induces body weight loss and browning of subcutaneous white adipose tissue through enhanced expression of hepatic fibroblast growth factor 21 (FGF21).
abstract: Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic candidate for the treatment of obesity. Since FGF21 production is regulated by various nutritional factors, we analyze the impact of low protein intake on circulating levels of this growth hormone in mice and in a sub cohort of the PREDIMED (Prevención con Dieta Mediterránea) trial. We also describe the role of hepatic FGF21 in metabolic adaptation to a low-protein diet (LPD).
  
  
  
  We fed control and liver-specific Fgf21 knockout (LFgf21KO) mice a LPD. This diet increased FGF21 production by inducing its overexpression in liver, and this correlated with a body weight decrease without changes in food intake. The LPD also caused FGF21-dependent browning in subcutaneous white adipose tissue (scWAT), as indicated by an increase in the expression of uncoupling protein 1 (UCP1). In a subgroup of 78 individuals from the PREDIMED trial, we observed an inverse correlation between protein intake and circulating FGF21 levels.
  
  
  
  Our results reinforce the involvement of FGF21 in coordinating energy homeostasis under a range of nutritional conditions. Moreover, here we describe an approach to increase the endogenous production of FGF21, which if demonstrated functional in humans, could generate a treatment for obesity.
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Pérez-Martí
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Garcia-Guasch
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Insitute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Barcelona, Spain.|CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Tresserra-Rimbau
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Carrilho-Do-Rosário
authors.affiliation: CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain.|Department of Internal Medicine, Hospital Clinic, IDIBAPS, University of Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Estruch
authors.affiliation: CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain.|Human Nutrition Department, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, University Rovira i Virgili, Reus (Tarragona), Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
authors.affiliation: CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain.|Department of Preventive Medicine and Public Health, Universidad de Navarra-Institute of Health Research of Navarra (IDISNA), Pamplona, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Martínez-González
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Insitute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Barcelona, Spain.|CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lamuela-Raventós
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Marrero
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Haro
authors.affiliation: Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, Torribera Food Campus, Santa Coloma de Gramenet, Barcelona, Spain.|Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Relat
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D052436:Adipose Tissue, White / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018753:Diet, Protein-Restricted; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000502:physiology; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D015431:Weight Loss / Q000235:genetics
chemical_list: C081452:Atf4 protein, mouse; C414620:fibroblast growth factor 21; D051701:Activating Transcription Factor 4; D005346:Fibroblast Growth Factors
keywords: Adipose tissue; Browning; Fibroblast growth factor 21; Low-protein diet; Uncoupling protein 1