Objective— To examine the association between liver fat content and very low-density lipoprotein (VLDL)–apolipoprotein (apo) B-100 kinetics and the corresponding responses to weight loss in obese subjects. Methods and Results— VLDL–apoB-100 kinetics were assessed using stable isotope tracers, and the fat content of the liver and abdomen was determined by magnetic resonance techniques in 25 obese subjects. In univariate analysis, liver fat content was significantly ( P <0.05 in all) associated with body mass index ( r =0.65), visceral fat area ( r =0.45), triglycerides ( r =0.40), homeostasis model assessment score ( r =0.40), VLDL–apoB-100 concentrations ( r =0.44), and secretion rate ( r =0.45). However, liver fat content was not associated with plasma concentrations of retinol-binding protein 4, fetuin A, adiponectin, interleukin-6, and tumor necrosis factor-α. Of these 25 subjects, 9 diagnosed as having nonalcoholic fatty liver disease (which is highly prevalent in obese individuals and strongly associated with dyslipidemia) underwent a weight loss program. The low-fat diet achieved significant reduction in body weight, body mass index, liver fat, visceral and subcutaneous fat areas, homeostasis model assessment score, triglycerides, VLDL–apoB-100 concentrations, and VLDL–apoB-100 secretion rate. The percentage reduction of liver fat with weight loss was significantly associated with the corresponding decreases in VLDL–apoB-100 secretion ( r =0.67) and visceral fat ( r =0.84). Conclusion— In patients with obesity, hepatic steatosis increases VLDL–apoB-100 secretion. Weight loss can help reduce this abnormality.