2134/11354099.v1
Scott Willis
Scott
Willis
Jack Sargeant
Jack
Sargeant
Tom Yates
Tom
Yates
Toshinari Takamura
Toshinari
Takamura
Hiroaki Takayama
Hiroaki
Takayama
Vinay Gupta
Vinay
Gupta
Emily Brittain
Emily
Brittain
Joe Crawford
Joe
Crawford
Sion Parry
Sion
Parry
Alice Thackray
Alice
Thackray
Veronica Varela-Mato
Veronica
Varela-Mato
David Stensel
David
Stensel
Rachel Woods
Rachel
Woods
Carl Hulston
Carl
Hulston
Guruprasad Aithal
Guruprasad
Aithal
James King
James
King
Acute hyper-energetic, high-fat feeding increases circulating FGF21, LECT2 and fetuin-A in healthy men
Loughborough University
2019
Hepatokines
overfeeding
high-fat diet
insulin resistance
FGF21
LECT2
Fetuin-B
Fetuin-A
Selenoprotein-P
Nutrition & Dietetics
Nutrition and Dietetics
Animal Production
Food Sciences
2019-12-12 13:09:33
Journal contribution
https://repository.lboro.ac.uk/articles/journal_contribution/Acute_hyper-energetic_high-fat_feeding_increases_circulating_FGF21_LECT2_and_fetuin-A_in_healthy_men/11354099
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.