Fibroblast growth factor-21 controls dietary protein intake in male mice
Open accessAbstract
Whereas carbohydrates and lipids are stored as glycogen and fat, there is no analogous inert storage form of protein. Therefore, continuous adjustments in feeding behavior are needed to match amino acid supply to ongoing physiologic need. Neuroendocrine mechanisms facilitating this behavioral control of protein and amino acid homeostasis remain unclear. The hepatokine fibroblast growth factor-21 (FGF21) is well positioned for such a role, as it is robustly secreted in response to protein and/or amino acid deficit. In this study, we tested the hypothesis that FGF21 feeds back at its receptors in the nervous system to shift macronutrient selection toward protein. In a series of behavioral tests, we isolated the effect of FGF21 to influence consumption of protein, fat, and carbohydrate in male mice. First, we used a three-choice pure macronutrient-diet paradigm. In response to FGF21, mice increased consumption of protein while reducing carbohydrate intake, with no effect on fat intake. Next, to determine whether protein or carbohydrate was the primary-regulated nutrient, we used a sequence of two-choice experiments to isolate the effect of FGF21 on preference for each macronutrient. Sweetness was well controlled by holding sucrose constant across the diets. Under these conditions, FGF21 increased protein intake, and this was offset by reducing the consumption of either carbohydrate or fat. When protein was held constant, FGF21 had no effect on macronutrient intake. Lastly, the effect of FGF21 to increase protein intake required the presence of its co-receptor, β-klotho, in neurons. Taken together, these findings point to a novel liver→nervous system pathway underlying the regulation of dietary protein intake via FGF21.
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When protein was fixed and mice selected between carbohydrate vs fat-rich diets, FGF21 treatment did not alter preference.
“when protein was fixed and mice selected between carbohydrate vs fat-rich diets, FGF21 treatment did not alter preference”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [184]
When either fat or carbohydrate was fixed, FGF21 significantly increased the consumption of the protein-rich diet.
“When either fat or carbohydrate was fixed, FG21 significantly increased the consumption of the protein-rich diet.”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [184]
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- Authors
- Larson, K. R., Chaffin, A. T.-B., Goodson, M. L., Fang, Y., & Ryan, K. K.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Ryan, Karen K
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2019-02-25
- Volume
- 160
- Issue
- 5
- Pages
- 1069-1080
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC6469953
- OpenAlex
- W2916356589
- Cited by
- 68
- References
- 75
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 13 · 2022: 10 · 2021: 7 · 2020: 6 · 2019: 5
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R56 DK117412)
- UC Davis College of Biological Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- FGF21, protein intake, macronutrient preference, amino acid homeostasis, β-Klotho, feeding behavior, sucrose preference, male mice
- MeSH terms
- Klotho Proteins, Animals, Dietary Carbohydrates, Dietary Proteins, Eating, Feeding Behavior, Fibroblast Growth Factors, Liver, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Nervous System, Neurons, Mice, Knockout
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