Differential effects of protein intake versus intake of a defined oligopeptide on FGF-21 in obese human subjects in vivo

Introduction Protein intake is one driver of circulating FGF-21 levels. The study aimed to gain deeper insight into the regulation of FGF-21 by protein intake in obese human subjects.

Subjects and Methods FGF-21 serum concentrations were measured in 246 obese subjects +/- type 2 diabetes mellitus (T2DM) and related to the nutritional protein intake. Additionally, the effect of a novel oligopeptide (β-casein hydrolysate) on FGF-21 was examined in vitro in liver cells and in vivo in a human intervention study including 40 obese subjects in a cross-over design.

Results In the cohort analysis, FGF-21 serum concentrations were significant lower with higher protein intake in obese subjects without T2DM but not in obese subjects with T2DM. No association was found for the dietary amount of methionine. While global protein intake in obesity was inversely associated with FGF-21, incubation of HepG2 cells with a β-casein oligopeptide increased FGF-21 expression in vitro. This stimulatory effect was also present in vivo, since in the clinical intervention study treatment of obese subjects with the β-casein oligonucleotide for 8 weeks significantly increased FGF-21 serum levels from t0=23.86 pg/ml to t8=30.54 pg/ml (p= 0.000), while no increase was found for placebo.

Main conclusions While the total nutritional protein intake is inversely associated with FGF-21 serum levels, a purified and defined oligopeptide is able to induce FGF-21 serum levels in humans. These findings suggest a differential role of various components of protein metabolism on FGF-21, rather than this factor being solely a sensor of total nutritional protein intake.

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Publication History

Article published online:
06 May 2021