FGF21 response to sucrose is associated with BMI and dorsal striatal signaling in humans

This study examined associations between BMI and dietary sugar intake with sucrose-induced fibroblast growth factor 21 (FGF21) and whether circulating FGF21 is associated with brain signaling following sucrose ingestion in humans.

A total of 68 adults (29 male; mean [SD), age 23.2 [3.8] years; BMI 27.1 [4.9] kg/m² ) attended visits after a 12-hour fast. Plasma FGF21 was measured at baseline and at 15, 30, and 120 minutes after sucrose ingestion (75 g in 300 mL of water). Brain cerebral blood flow responses to sucrose were measured using arterial spin labeling magnetic resonance imaging.

Higher circulating FGF21 levels were associated with reduced blood flow in the striatum in response to sucrose (β = -7.63, p = 0.03). This association was greatest among persons with healthy weight (β = -15.70, p = 0.007) and was attenuated in people with overweight (β = -4.00, p = 0.63) and obesity (β = -12.45, p = 0.13). BMI was positively associated with FGF21 levels in response to sucrose (β = 0.53, p = 0.02). High versus low dietary sugar intake was associated with greater FGF21 responses to acute sucrose ingestion in individuals with healthy weight (β = 8.51, p = 0.04) but not in individuals with overweight or obesity (p > 0.05).

These correlative findings support evidence in animals showing that FGF21 acts on the brain to regulate sugar consumption through a negative feedback loop.