Acute Hyperenergetic, High-Fat Feeding Increases Circulating FGF21, LECT2, and Fetuin-A in Healthy Men

Willis, Scott A.; Sargeant, Jack A.; Yates, Thomas; Takamura, Toshinari; Takayama, Hiroaki; Gupta, Vinay; Brittain, Emily; Crawford, Joe; Parry, Si�n A.; Thackray, Alice E.; Varela-Mato, Veronica; Stensel, David J.; Woods, Rachel M.; Hulston, Carl J.; Aithal, Guruprasad P.; King, James A.

Abstract

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 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

Citation

Willis, S. A., Sargeant, J. A., Yates, T., Takamura, T., Takayama, H., Gupta, V., …King, J. A. (2020). Acute Hyperenergetic, High-Fat Feeding Increases Circulating FGF21, LECT2, and Fetuin-A in Healthy Men. Journal of Nutrition, 150(5), 1076–1085. https://doi.org/10.1093/jn/nxz333

• Journal Article Type: Article
• Acceptance Date: Dec 12, 2019
• Online Publication Date: Jan 9, 2020
• Publication Date: 2020-05
• Deposit Date: Jan 13, 2020
• Publicly Available Date: Jan 10, 2021
• Journal: Journal of Nutrition
• Print ISSN: 0022-3166
• Electronic ISSN: 1541-6100
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 150
• Issue: 5
• Pages: 1076–1085
• DOI: https://doi.org/10.1093/jn/nxz333
• Keywords: Nutrition and Dietetics; Medicine (miscellaneous)
• Public URL: https://nottingham-repository.worktribe.com/output/3717517
• Publisher URL: https://academic.oup.com/jn/advance-article/doi/10.1093/jn/nxz333/5699656
• Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in 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, , nxz333; is available online at: https://doi.org/10.1093/jn/nxz333