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To determine whether, in accordance with observations in mouse models, high concentrations of the lipoprotein lipase inhibitors apolipoprotein (Apo) CI and ApoCIII are associated with increased triglyceride concentrations and decreased fat mass in men with the metabolic syndrome.Plasma ApoCI, ApoCIII, and triglyceride concentrations were measured in the postabsorptive state in 98 men with the metabolic syndrome. Subcutaneous and visceral fat areas were measured by 3T-magnetic resonance imaging.Triglyceride concentrations were 49% higher, and the average visceral fat area was 26% lower (both P < 0.001), in subjects with high ApoCI and ApoCIII compared with low ApoCI and ApoCIII. Subjects with either high ApoCI or ApoCIII had 16% (P < 0.05) and 18% (P < 0.01) decreased visceral fat area, respectively.High concentrations of ApoCI and ApoCIII are associated with increased triglycerides and decreased visceral fat mass in men with the metabolic syndrome. These findings translate mouse studies into human pathophysiology.