Objective: To examine the association between the kinetics of very-low-density-lipoprotein (VLDL)-apolipoprotein B-100 (apoB) and intraperitoneal, retroperitoneal, subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM, and TATM, respectively) in overweight/obese men.Research Methods and Procedures: Hepatic secretion of VLDL was measured using an intravenous infusion of 1-[C-13]- leucine in 51 men with a wide range of body mass index (25.1 to 42.2 kg/m(2)). Isotopic enrichment of VLDL-apoB was measured using gas chromatography-mass spectrometry and a multicompartmental model used to estimate VLDL-apoB metabolic parameters. IPATM, RPATM, and SAATM (kilograms) were quantified between T11 and S1 using magnetic resonance imaging; TATM (kilograms) was determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score.Results: In stepwise regression, IPATM was the best predictor of hepatic secretion of VLDL-apoB (r = 0.390, p < 0.005) and TATM was the best predictor of VLDL-apoB fractional catabolic rate (r = 0.282, p < 0.05). IPATM remained significantly associated with VLDL-apoB secretion after adjusting for TATM or HOMA score (r = 0.360, P < 0.01 and r = 0.310, p < 0.05, respectively). This association was also independent of age, dietary intake, and body mass index. None of the fat compartments were significantly associated with the fractional catabolic rate of VLDL-apoB after adjusting for HOMA score.Discussion: In overweight/obese men, the quantity of both IPATM and TATM determine the kinetics of VLDL-apoB. The effect of IPATM on VLDL-apoB secretion is independent of both total fat mass and the degree of insulin resistance.