Willis et al J Nutr Overfeeding and hepatokines.docx (185.77 kB)
Acute hyper-energetic, high-fat feeding increases circulating FGF21, LECT2 and fetuin-A in healthy men
journal contribution
posted on 2019-12-12, 13:09 authored by Scott Willis, Jack Sargeant, Tom Yates, Toshinari Takamura, Hiroaki Takayama, Vinay Gupta, Emily Brittain, Joe Crawford, Sion Parry, Alice ThackrayAlice Thackray, Veronica Varela-MatoVeronica Varela-Mato, David StenselDavid Stensel, Rachel Woods, Carl Hulston, Guruprasad Aithal, James KingJames KingBackground: 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 which 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: To investigate the influence of hyper-energetic, high-fat feeding on circulating hepatokine concentrations, including the time-course of responses.
Methods: In a randomised, crossover design, 12 healthy men (mean ± SD: age, 24 ± 4 years; BMI, 24.1 ± 1.5 kg∙m-2) consumed a seven-day hyper-energetic, 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 three weeks. 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 analysed using two-way repeated-measures ANOVA and subsequent pairwise comparisons.
Results: Compared with control, the HE-HFD increased circulating FGF21 at 1 (105%) and 3 d (121%; P 0.040); LECT2 at 3 (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 levels 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.
Funding
National Institute for Health Research (NIHR) Leicester and Nottingham Biomedical Research Centres
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School
- Sport, Exercise and Health Sciences
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The Journal of NutritionVolume
150Issue
5Pages
1076 - 1085Publisher
Oxford University Press (OUP)Version
- AM (Accepted Manuscript)
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© The AuthorsPublisher statement
This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Nutrition following peer review. The version of record Scott A Willis, Jack A Sargeant, Thomas Yates, Toshinari Takamura, Hiroaki Takayama, Vinay Gupta, Emily Brittain, Joe Crawford, Siôn A Parry, Alice E Thackray, Veronica Varela-Mato, David J Stensel, Rachel M Woods, Carl J Hulston, Guruprasad P Aithal, James A King, Acute Hyperenergetic, High-Fat Feeding Increases Circulating FGF21, LECT2, and Fetuin-A in Healthy Men, The Journal of Nutrition, Volume 150, Issue 5, May 2020, Pages 1076–1085 is available online at: https://academic.oup.com/jn/article/150/5/1076/5699656 and https://doi.org/10.1093/jn/nxz333.Acceptance date
2019-12-10Publication date
2020-01-09Copyright date
2020ISSN
0022-3166Publisher version
Language
- en
Depositor
Dr James King Deposit date: 11 December 2019Usage metrics
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