Acute hyperenergetic, high-fat feeding increases circulating FGF21, LECT2, and fetuin-A in healthy men
Open accessAbstract
Background Hepatokines such as fibroblast growth factor 21 (FGF21), leukocyte cell-derived chemotaxin 2 (LECT2), fetuin-A, fetuin-B, and selenoprotein P (SeP) are liver-derived proteins that are modulated by chronic energy status and metabolic disease. Emerging data from rodent and cell models indicate that hepatokines may be sensitive to acute nutritional manipulation; however, data in humans are lacking.Objective The aim was to investigate the influence of hyperenergetic, high-fat feeding on circulating hepatokine concentrations, including the time course of responses.Methods In a randomized, crossover design, 12 healthy men [mean ± SD: age, 24 ± 4 y; BMI (kg/m2), 24.1 ± 1.5] consumed a 7-d hyperenergetic, high-fat diet [HE-HFD; +50% energy, 65% total energy as fat (32% saturated, 26% monounsaturated, 8% polyunsaturated)] and control diet (36% total energy as fat), separated by 3 wk. Whole-body insulin sensitivity was assessed before and after each diet using oral-glucose-tolerance tests. Fasting plasma concentrations of FGF21 (primary outcome), LECT2, fetuin-A, fetuin-B, SeP, and related metabolites were measured after 1, 3, and 7 d of each diet. Hepatokine responses were analyzed using 2-factor repeated-measures ANOVA and subsequent pairwise comparisons.Results Compared with the control, the HE-HFD increased circulating FGF21 at 1 d (105%) and 3 d (121%; P ≤ 0.040), LECT2 at 3 d (17%) and 7 d (32%; P ≤ 0.004), and fetuin-A at 7 d (7%; P = 0.028). Plasma fetuin-B and SeP did not respond to the HE-HFD. Whole-body insulin sensitivity was reduced after the HE-HFD by 31% (P = 0.021).Conclusions Acute high-fat overfeeding augments circulating concentrations of FGF21, LECT2, and fetuin-A in healthy men. Notably, the time course of response varies between proteins and is transient for FGF21. These findings provide further insight into the nutritional regulation of hepatokines in humans and their interaction with metabolic homeostasis. This study was registered at clinicaltrials.gov as NCT03369145.
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Acute high-fat diet overfeeding increases circulating concentrations of LECT2 in healthy men.
“Recent research demonstrated that acute high-fat diet overfeeding increased circulating concentrations of LECT2 in healthy men [251].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [251]
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- Willis SA, King JA, Parry SA, Woods RM, Sargeant JA, Hulston CJ. The effect of acute, high-fat overfeeding on circulating hepatokine concentrations in BASES Conference 2018-programme and abstracts. J Sports Sci 2018;38(Suppl 1):60.
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Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252 · see citing works
- Authors
- Willis, S. A., Sargeant, J. A., Yates, T., Takamura, T., Takayama, H., Gupta, V., Brittain, E., Crawford, J., Parry, S. A., Thackray, A. E., Varela-Mato, V., Stensel, D. J., Woods, R. M., Hulston, C. J., Aithal, G. P., & King, J. A.
- Affiliations
- National Health Service (GB)
- Kanazawa University (JP)
- Loughborough University (GB)
- Nottingham University Hospitals NHS Trust (GB)
- Corresponding author
- King, James A
- ORCID
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 150
- Issue
- 5
- Pages
- 1076-1085
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2995242501
- Cited by
- 34
- References
- 71
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 9 · 2021: 4 · 2020: 6
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (acceptedVersion, other-oa)
- Figshare (submittedVersion, cc-by-nc-nd)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institute for Health Research
- Leicester and Nottingham Biomedical Research Centers
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- hepatokines, FGF21, LECT2, fetuin-A, fetuin-B, selenoprotein P, overfeeding, insulin sensitivity, healthy men, energy status, time-course response
- MeSH terms
- Adult, Blood Glucose, Energy Intake, Fibroblast Growth Factors, Gene Expression Regulation, Humans, Insulin, Liver, Male, Cross-Over Studies, Intercellular Signaling Peptides and Proteins, Young Adult, Diet, High-Fat, alpha-2-HS-Glycoprotein
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