Background and Aim: Interval training by improving insulin sensitivity and betaine by reducing hepatic lipogenesis each have the ability to modulate metabolic disorders caused by obesity. The aim of this study was to investigate the effect of moderate-intensity interval training (MIIT) along with nanoemulsified betaine supplementation on the hepatic expression of glucose transporter-4 (GLUT4), sterol regulatory element binding protein 1c (SREBP-1c), liver X receptor-alpha (LXRα), and Kröppel-like factor-15 (KLF15) genes in obese rats. Materials and Methods: 25 rats were divided into five equal groups including healthy control, obese control, obese+MIIT, obese+nanoemulsified betaine, and obese+MIIT+nanoemulsified betaine. The obese groups were fed a high-fat-cholesterol diet for 12 weeks. MIIT protocol was performed for eight weeks, including 30-minute running, with activity bouts speed of 10 to 16 m/min, five days a week; Nanoemulsified betaine supplementation was administered by gavage at a dose of 50 mg/kg body weight. The hepatic expression of GLUT4, SREBP-1c, LXRα, and KLF15 genes was examined by qRT-PCR. Data were analyzed by independent t-tests and two-way analysis of variance at the p≤0.05 level. Findings: Obesity decreased the expression of GLUT4 and KLF15 and increased SREBP-1c and LXRα (p≤0.001 for all genes). MIIT and supplementation each separately increased GLUT4, KLF15 and also decreased SREBP-1c and LXRα (p≤0.001 for both interventions; for all genes). The interaction of the two interventions only significantly reduced SREBP-1c (p=0.017). Conclusion: MIIT and nanoemulsified betaine interventions each independently modulate the expression pattern of hepatic metabolic genes to improve insulin resistance and reduce lipogenesis. However, the interaction of these two interventions and their synergistic effect only specifically causes stronger suppression of SREBP-1c, which could be important in reducing hepatic lipogenesis and improving obesity-related fatty liver.