Modulation of Insulin Sensitivity by Betaine Upregulation of FGF21

AIM: To determine if betaine is a modulator of FGF21 in humans. Low plasma betaine is associated with an increased risk of metabolic syndrome, but the mechanisms modulating this correlation are poorly delineated. Betaine bioavailability in humans is determined by dietary intake and genetic polymorphisms that influence betaine metabolism. Therefore, moderating betaine levels could be particularly beneficial for some individuals. FGF21 is elevated in response to insulin insensitivity and is under active investigation as a therapeutic modality. The mechanisms of action of FGF21 and betaine on insulin sensitivity in humans are incompletely understood. This study tests the hypothesis that betaine induces FGF21 secretion and insulin sensitizing actions in humans by measuring plasma FGF21, betaine, choline (betaine precursor), glucose, insulin and adiponectin in response to betaine supplementation over a 24 hour time course in 20 healthy, lean individuals. This pilot nutrition intervention will provide key preliminary evidence for understanding whether and how betaine exerts metabolic benefit in humans and will inform a future study to investigate the novel betaine-FGF21-insulin sensitivity axis in a larger cohort.