Niemann-Pick Disease Type C1 Modulates Hepatic Triglyceride Metabolism and Its Genetic Variation Contributes to Serum Triglyceride Levels

to determine whether this is reflected in circulating lipid levels. Methods and Results—In Npc1 / mice, the hepatic cholesterol content is increased but the TG content is decreased. We investigated lipid metabolism in Npc1 / mouse hepatocytes and the association of NPC1 single-nucleotide polymorphisms with circulating TGs in humans. TGs were reduced in Npc1 / mouse serum and hepatocytes. In Npc1 / hepatocytes, the incorporation of [H]oleic acid and [H]acetate into TG was decreased, but shunting of oleic acidor acetate-derived [H]carbons into cholesterol was increased. The inhibition of cholesterol synthesis normalized TG synthesis, content, and secretion in Npc1 / hepatocytes, suggesting increased hepatic cholesterol neogenesis as a