To examine associations of dietary changes from childhood to adolescence with adolescent hepatic fat and whether the PNPLA3 rs738409 risk allele, a strong genetic risk factor for hepatic fat, modifies associations.

Data were from 358 participants in the Exploring Perinatal Outcomes among CHildren (EPOCH) study, a longitudinal cohort in Colorado. Diet was assessed by food frequency questionnaire in childhood (approximately 10 years of age) and adolescence (approximately 16 years of age) and converted to nutrient densities. Hepatic fat was assessed in adolescence by magnetic resonance imaging. Linear regression was used to test associations of dietary changes from childhood to adolescence with adolescent hepatic fat.

Increases in fiber, vegetable protein, and polyunsaturated fat intake from childhood to adolescence were associated with lower adolescent hepatic fat, and increases in animal protein were associated with higher hepatic fat (β per 5-unit increase on log-hepatic fat: −0.12 [95% CI, −0.21 to −0.02] for ▵fiber; −0.26 [95% CI, −0.45 to −0.07] for ▵vegetable protein; −0.18 [95% CI, −0.35 to −0.02] for ▵polyunsaturated fat; 0.13 [95% CI, 0.04-0.22] for ▵animal protein). There was evidence of effect modification by PNPLA3 variant, whereby inverse associations of ▵fiber and ▵vegetable protein and positive associations of ▵saturated fat with adolescent hepatic fat were stronger in risk allele carriers. Most conclusions were similar after adjusting for obesity in adolescence, but associations of ▵saturated fat with hepatic fat were attenuated toward the null.

Our results suggest that nutrient intake changes between childhood and adolescence, particularly decreases in fiber and vegetable protein and increases in saturated fat intake, interact with the PNPLA3 variant to predict higher hepatic fat in adolescence, and may be targets for reducing hepatic fat in high-risk youth.