Abstract

Latino youths with obesity are disproportionately impacted by nonalcoholic fatty liver disease (NAFLD). Lifestyle intervention can improve established biomarkers such as serum transaminases and hepatic fat fraction (HFF) in NAFLD patients. Circulating levels of extracellular vesicles (EVs) have been associated with NAFLD and may track with changes in liver fat. Here we assessed changes in EV concentration and size following a comprehensive lifestyle intervention in 18 Latino adolescents (12 males/6 females; average age 13.3 ±1.2y) with obesity and NAFLD, as defined by MRI-measured hepatic fat fraction (HFF) ≥5%. Participants completed a 6-month lifestyle intervention that targeted improvements in eating behaviors (e.g., decreased sugar and saturated fat intake, portion control, and increased fiber intake) and increases in physical activity. EVs were isolated from fasting plasma samples taken at baseline and following intervention using size exclusion chromatography and characterized by nanoparticle tracking analysis. Significant improvements (pre- vs post-intervention) were observed in percent body fat (44.7 ±4.8% vs 42.2 ±5.3%, p<0.0001), alanine transaminase (ALT; 24.8 ±7.4 U/L vs 23.2 ±5.6 U/L p=0.02), and HFF (12.5 ±5.5% vs 9.6 ±4.9%, p=0.008). We observed a significant reduction in mean EV size (128.4 ±16.5 vs 120.2 ±16.4, p=0.03) and a non-significant reduction in EV concentration (1.14E+09 ±4.1E+08 vs 1.09E+09 ±1.8E+08, p=0.61) following the intervention. Change in mean EV size was significantly and positively associated with changes in SAT (cm3), HDL (mg/dl), fat (kg) and BMI (all p < 0.05). These results suggest that improvements in NAFLD-related phenotypes following lifestyle intervention correspond with reductions in EV size in Latino adolescents with obesity and NAFLD. Disclosure I. Piras: None. X. Wu: None. P. Pirrotte: None. M. Olson: Advisory Panel; Rhythm Pharmaceuticals, Inc. S. Khan: None. S. Xanthakos: None. G. Q. Shaibi: None. J. Distefano: None. Funding National Institutes of Health (R01DK127015)

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