Raised FGF-21 and triglycerides accompany increased energy intake driven by protein leverage in lean, healthy individuals: a randomised trial
Open accessAbstract
A dominant appetite for protein drives increased energy intake in humans when the proportion of protein in the diet is reduced down to approximately 10% of total energy. Compensatory feeding for protein is apparent over a 1–2 d period but the mechanisms driving this regulation are not fully understood. Fibroblast growth factor-21 (FGF-21) has been identified as a candidate protein signal as levels increase in the circulation when dietary protein is low. The aim of this randomised controlled trial was to assess whether changes in percent dietary protein over a 4 d ad libitum experimental period in lean, healthy participants influenced energy intake, metabolic health, circulating FGF-21 and appetite regulating hormones including ghrelin, glucagon like peptide-1 and cholecystokinin. Twenty-two lean, healthy participants were fed ad libitum diets containing 10, 15 and 25% protein, over three, 4 d controlled, in-house experimental periods. Reduced dietary protein intake from 25% to 10% over a period of 4 d was associated with 14% increased energy intake (p = 0.02) as previously reported, and a 6-fold increase in fasting circulating plasma FGF-21 levels (p<0.0001), a 1.5-fold increase in serum triglycerides (p<0.0001), and a 0.9-fold decrease in serum total cholesterol (p = 0.02). Serum HDL cholesterol was reduced with a reduction in dietary protein from 15% to 10% (p = 0.01) over 4 d but not from 25% to 10% (p = 0.1) and the change from baseline was not different between diets. Plasma fasting insulin levels following the 4 d study period were significantly lower following the 25% ad libitum study period compared to the 15% protein period (p = 0.014) but not the 10% protein period (p = 0.2). Variability in interstitial glucose during each study period increased with a decrease in dietary protein from 25% to 15% and 10% (p = 0.001 and p = 0.04, respectively). Ghrelin, glucagon-like peptide-1 and cholecystokinin were unchanged. Increases in energy intake, plasma FGF-21 and serum triglycerides were associated with reductions in percent dietary protein from 25% to 10% energy over a 4 d ad libitum in-house feeding period and may be important in regulation of dietary protein intake. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12616000144415.
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Liver FGF21 expression and circulating FGF21 protein levels are increased by the restriction of protein intake in mice, rats, and humans.
“liver FGF21 expression and circulating FGF21 protein levels are increased by the restriction of protein intake in mice, rats, and humans”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [150]
Reductions in dietary protein intake-or the intake of specific amino acids-increase liver FGF21 mRNA expression and circulating FGF21 protein levels.
“reductions in dietary protein intake—or the intake of specific amino acids—increase liver FGF21 mRNA expression and circulating FGF21 protein levels”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [150]
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- Authors
- Gosby, A. K., Lau, N. S., Tam, C. S., Iglesias, M. A., Morrison, C. D., Caterson, I. D., Brand-Miller, J., Conigrave, A. D., Raubenheimer, D., & Simpson, S. J.
- Affiliations
- The University of Sydney (AU)
- University of Tasmania (AU)
- Pennington Biomedical Research Center (US)
- Corresponding author
- Gosby, Alison K.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-08-18
- Volume
- 11
- Issue
- 8
- Pages
- e0161003
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4990330
- OpenAlex
- W2507415157
- Cited by
- 51
- References
- 57
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 2 · 2016: 1
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UTAS Research Repository (acceptedVersion)
- eCite Digital Repository (University of Tasmania) (acceptedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council (457522, 1037275)
- 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
- dietary protein reduction, energy intake regulation, triglycerides, HDL cholesterol, total cholesterol, fasting insulin, ghrelin, glucagon-like peptide-1, cholecystokinin, appetite-regulating hormones, ad libitum feeding, metabolic health, energy homeostasis
- MeSH terms
- Adolescent, Adult, Blood Glucose, Energy Intake, Cholecystokinin, Dietary Proteins, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, Triglycerides, Glucagon-Like Peptide 1, Ghrelin, Young Adult
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