This study aimed to investigate the mechanism by which aerobic swimming training prevents high-fatdiet-induced nonalcoholic fatty liver disease (NAFLD). Forty-two male C57BL/6 mice were randomized into normal-diet sedentary (ND; n = 8), ND exercised (n = 8), high-fat diet sedentary (HFD; n = 13), and HFD exercised groups (n = 13). After 2 weeks of training adaptation, the mice were subjected to an aerobic swimming protocol (60 min/day) 5 days/week for 10 weeks. The HFD group exhibited significantly higher mRNA levels of fatty acid transport-, lipogenesis-, and beta-oxidation-associated gene expressions than the ND group. PANDER and FOXO1 expressions increased, whereas ART expression decreased in the HFD group. The aerobic swimming program with the HFD reversed the effects of the HFD on the expressions of thrombospondin-1 receptor, liver fatty acid-binding protein, long-chain fatty-acid elongase-6, Fas cell surface death receptor, and stearoyl-coenzyme A desaturase-1, as well as PANDER, FOXO1, and AKT. In the HFD exercised group, PPAR alpha and AOX expressions were much higher. Our findings suggest that aerobic swimming training can prevent NAFLD via the regulation of fatty acid transport-, lipogenesis-, and beta-oxidation-associated genes. In addition, the benefits from aerobic swimming training were achieved partly through the PANDER-AICT-FOXO1 pathway. (C) 2015 Elsevier Inc. All rights reserved.