Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates

TY - JOUR

T1 - Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates

AU - Lundsgaard, Annemarie

AU - Fritzen, Andreas Mæchel

AU - Sjøberg, Kim Anker

AU - Myrmel, Lene S

AU - Madsen, Lise

AU - Wojtaszewski, Jørgen

AU - Richter, Erik

AU - Kiens, Bente

N1 - CURIS 2017 NEXS 048

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Objective Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. Methods A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. Results After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml−1, p < 0.05). In contrast, after FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01) with increased leg glucose uptake (62%, p < 0.05) and increased hepatic glucose production (17%, p < 0.01), indicating increased glucose turnover. Plasma fatty acid (FA) concentration was decreased by 68% (p < 0.01), supported by reduced subcutaneous adipose tissue HSL Ser660 phosphorylation (p < 0.01) and perilipin 1 protein content (p < 0.01), pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the plasma marker of hepatic de novo lipogenesis C16:1 n−7 FA (p < 0.01) was observed together with 101% increased plasma TG concentration (p < 0.001) in association with CHO intake and increased plasma FGF21 concentration. Conclusion Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.

AB - Objective Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. Methods A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. Results After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml−1, p < 0.05). In contrast, after FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01) with increased leg glucose uptake (62%, p < 0.05) and increased hepatic glucose production (17%, p < 0.01), indicating increased glucose turnover. Plasma fatty acid (FA) concentration was decreased by 68% (p < 0.01), supported by reduced subcutaneous adipose tissue HSL Ser660 phosphorylation (p < 0.01) and perilipin 1 protein content (p < 0.01), pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the plasma marker of hepatic de novo lipogenesis C16:1 n−7 FA (p < 0.01) was observed together with 101% increased plasma TG concentration (p < 0.001) in association with CHO intake and increased plasma FGF21 concentration. Conclusion Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.

KW - Faculty of Science

KW - FGF21

KW - Diet

KW - Carbohydrates

KW - Lipolysis

KW - Liver

U2 - 10.1016/j.molmet.2016.11.001

DO - 10.1016/j.molmet.2016.11.001

M3 - Journal article

C2 - 28123934

SN - 2212-8778

VL - 6

SP - 22

EP - 29

JO - Molecular Metabolism

JF - Molecular Metabolism

IS - 1

ER -