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
SCOPE: 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). METHODS AND RESULTS: 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. CONCLUSION: 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.
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The increase in FGF21 in response to low protein results in increased energy expenditure and lower body weight gain.
“This robust increase in FGF21 results in increased energy expenditure and lower body weight gain [155,156,160,163] (Figure 2)”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [160]
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Influência de dieta desbalanceada hipoproteica na imunidade tecido-específica da mucosa intestinal
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Lipid Response to Amino Acid Starvation in Fat Cells: Role of FGF21
Pérez‐Martí, A., Marrero, P. F., Haro, D., & Relat, J. (2017) · Springer eBooks · doi:10.1007/978-3-319-40007-5_15-1
Restriction of essential amino acids dictates the systemic response to dietary protein dilutionPreprint
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Adipose Tissue Browning in MASLD and Its Molecular Mechanisms and Metabolic Crosstalk
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Revisiting gut microbiota-driven ammonia metabolism: from disease burden to physiological adaptation
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- Authors
- Pérez‐Martí, A., Garcia‐Guasch, M., Tresserra‐Rimbau, A., Carrilho‐Do‐Rosário, A., Estruch, R., Salas‐Salvadó, J., Martínez‐González, M. Á., Lamuela‐Raventós, R., Marrero, P. F., Haro, D., & Relat, J.
- Affiliations
- Institut de Biomedicina de la Universitat de Barcelona (ES)
- Instituto de Salud Carlos III (ES)
- CIBEROBN Instituto de Salud Carlos III Madrid Spain
- 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
- Corresponding author
- Haro, Diego
- Relat, Joana
- ORCID
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2017-03-02
- Volume
- 61
- Issue
- 8
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2571982167
- Cited by
- 56
- References
- 42
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 11 · 2018: 5 · 2017: 3
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Funders
- Ministerio de Economía y Competitividad (SAF2013‐41093)
- Comisión Interministerial de Ciencia y Tecnología (AGL2013‐49083‐C3‐1‐R, AGL2016‐79113‐R)
- Universitat de Barcelona
- Instituto de Salud Carlos III
- Ministerio de Educación, Cultura y Deporte
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- FGF21, low-protein diet, weight loss, white adipose tissue browning, UCP1, obesity treatment, energy homeostasis, protein intake, PREDIMED trial, Mediterranean diet
- MeSH terms
- Aged, Aged, 80 and over, Animals, Female, Fibroblast Growth Factors, Gene Expression Regulation, Humans, Liver, Male, Middle Aged, Weight Loss, Mice, Knockout, Diet, Protein-Restricted, Activating Transcription Factor 4, Adipose Tissue, White
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