FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans

Abstract

The liking and selective ingestion of palatable foods-including sweets-is biologically controlled, and dysfunction of this regulation may promote unhealthy eating, obesity, and disease. The hepatokine fibroblast growth factor 21 (FGF21) reduces sweet consumption in rodents and primates, whereas knockout of Fgf21 increases sugar consumption in mice. To investigate the relevance of these findings in humans, we genotyped variants in the FGF21 locus in participants from the Danish Inter99 cohort (n = 6,514) and examined their relationship with a detailed range of food and ingestive behaviors. This revealed statistically significant associations between FGF21 rs838133 and increased consumption of candy, as well as nominal associations with increased alcohol intake and daily smoking. Moreover, in a separate clinical study, plasma FGF21 levels increased acutely after oral sucrose ingestion and were elevated in fasted sweet-disliking individuals. These data suggest the liver may secrete hormones that influence eating behavior.

A common allele in FGF21 associated with preference for sugar consumption lowers body fat in the lower body and increases blood pressure

“…These findings are consistent with data from animal studies showing that FGF21 signals to reward centres in the brain [1,2]. The human genetic studies found no detectable effect on the risk of type 2 diabetes and only nominal evidence for an effect on BMI [13].…”

“…These findings are consistent with data from animal studies showing that FGF21 signals to reward centres in the brain [1,2]. The human genetic studies found no detectable effect on the risk of type 2 diabetes and only nominal evidence for an effect on BMI [13].Here we aimed to extend the characterisation of the phenotypes associated with the variant in FGF21 using 451,000 individuals from the UK Biobank. We reasoned that genotype-phenotype associations of FGF21 would inform developers of FGF21 based therapies as to their potential beneficial and adverse effects.…”

“…Of these associations, only that with higher percentage carbohydrate intake was convincingly shown before [13].…”

“…Studies in mice and non human primates show that genetically and pharmacologically raising FGF21 levels suppresses sugar and alcohol intake [1,2]. Three human genetic studies have shown that the minor A allele at rs838133 (A/G, Minor Allele Frequency=44.7%), which results in a synonymous change to the first exon of FGF21, is associated with higher carbohydrate and lower protein and fat intake, with no effect on total calorie intake [12][13][14]. Soberg et al showed that the carbohydrate preference was specific to sugary products, and may also increase alcohol intake [13].…”

“…Three human genetic studies have shown that the minor A allele at rs838133 (A/G, Minor Allele Frequency=44.7%), which results in a synonymous change to the first exon of FGF21, is associated with higher carbohydrate and lower protein and fat intake, with no effect on total calorie intake [12][13][14]. Soberg et al showed that the carbohydrate preference was specific to sugary products, and may also increase alcohol intake [13]. These findings are consistent with data from animal studies showing that FGF21 signals to reward centres in the brain [1,2].…”