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

Abstract

ObjectiveFibroblast-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.MethodsA 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.ResultsAfter 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.ConclusionExcess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.

Fibroblast growth factor 21 and fructose dynamics in humans

“…A comparable increase in FGF21 levels has also been observed after ingestion of a 75 g oral sucrose load ; similar changes have not been seen with an oral glucose load . A 3 d high‐carbohydrate diet (80% carbohydrates, 52 g d −1 fructose) significantly increased FGF21 levels in lean humans . Furthermore, baseline fasting FGF21 levels are higher, and the FGF21 response to fructose is exaggerated in humans with metabolic syndrome compared with lean counterparts .…”

Fatty acid type–specific regulation of SIRT1 does not affect insulin sensitivity in human skeletal muscle

“…Subject characteristics are given in Table 1 . Subject characteristics for the Unsat group (17) and for all the 17 subjects as a whole (18) have been previously published.…”

Fibroblast growth factor 21: an endocrine inhibitor of sugar and alcohol appetite

“…A later study has controlled for this by providing young men with a carbohydrate‐rich diet with no change in protein content (Lundsgaard et al . ). This led to a higher energy content, but by including a diet where the excess energy was provided by fat instead of carbohydrates, it was controlled that the energy content itself was not the primary driver of FGF21 release.…”