Acute hyperenergetic, high-Fat feeding increases circulating FGF21, LECT2, and fetuin - A in healthy men

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*


研究成果: Article査読

22 被引用数 (Scopus)


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 as NCT03369145. J Nutr 2020;150:1076–1085.

ジャーナルJournal of Nutrition
出版ステータスPublished - 2020 5月 1

ASJC Scopus subject areas

  • 医学(その他)
  • 栄養および糖尿病


「Acute hyperenergetic, high-Fat feeding increases circulating FGF21, LECT2, and fetuin - A in healthy men」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。