TY - JOUR
T1 - Acute hyperenergetic, high-Fat feeding increases circulating FGF21, LECT2, and fetuin - A in healthy men
AU - Willis, Scott A.
AU - Sargeant, Jack A.
AU - Yates, Thomas
AU - Takamura, Toshinari
AU - Takayama, Hiroaki
AU - Gupta, Vinay
AU - Brittain, Emily
AU - Crawford, Joe
AU - Parry, Siôn A.
AU - Thackray, Alice E.
AU - Varela-Mato, Veronica
AU - Stensel, David J.
AU - Woods, Rachel M.
AU - Hulston, Carl J.
AU - Aithal, Guruprasad P.
AU - King, James A.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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. J Nutr 2020;150:1076–1085.
AB - 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. J Nutr 2020;150:1076–1085.
KW - Fetuin-A
KW - Fetuin-B
KW - FGF21
KW - Hepatokines
KW - High-fat diet
KW - Insulin resistance
KW - LECT2
KW - Overfeeding
KW - Selenoprotein P
UR - http://www.scopus.com/inward/record.url?scp=85091126794&partnerID=8YFLogxK
UR - https://www.sciencedirect.com/science/article/pii/S0022316622021757?via%3Dihub
U2 - 10.1093/jn/nxz333
DO - 10.1093/jn/nxz333
M3 - Article
C2 - 31919514
AN - SCOPUS:85091126794
SN - 0022-3166
VL - 150
SP - 1076
EP - 1085
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 5
ER -