{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:09:57Z","timestamp":1780405797985,"version":"3.54.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            To study how Niemann-Pick disease type C1 (NPC1) influences hepatic triacylglycerol (TG) metabolism and to determine whether this is reflected in circulating lipid levels.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            In\n            <jats:italic>\n              Npc1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            mice, the hepatic cholesterol content is increased but the TG content is decreased. We investigated lipid metabolism in\n            <jats:italic>\n              Npc1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            mouse hepatocytes and the association of\n            <jats:italic>NPC1<\/jats:italic>\n            single-nucleotide polymorphisms with circulating TGs in humans. TGs were reduced in\n            <jats:italic>\n              Npc1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            mouse serum and hepatocytes. In\n            <jats:italic>\n              Npc1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            hepatocytes, the incorporation of [\n            <jats:sup>3<\/jats:sup>\n            H]oleic acid and [\n            <jats:sup>3<\/jats:sup>\n            H]acetate into TG was decreased, but shunting of oleic acid- or acetate-derived [\n            <jats:sup>3<\/jats:sup>\n            H]carbons into cholesterol was increased. Inhibition of cholesterol synthesis normalized TG synthesis, content, and secretion in\n            <jats:italic>\n              Npc1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            hepatocytes, suggesting increased hepatic cholesterol neogenesis as a cause for the reduced TG content and secretion. We found a significant association between serum TG levels and 5 common\n            <jats:italic>NPC1<\/jats:italic>\n            single-nucleotide polymorphisms in a cohort of 1053 men, with the lowest\n            <jats:italic>P<\/jats:italic>\n            =8.7\u00d710\n            <jats:sup>\u22124<\/jats:sup>\n            for the single-nucleotide polymorphism\n            <jats:italic>rs1429934<\/jats:italic>\n            . The association between the\n            <jats:italic>rs1429934<\/jats:italic>\n            <jats:italic>A<\/jats:italic>\n            allele and higher TG levels was replicated in 2 additional cohorts, which included 8041 individuals.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            This study provides evidence of the following: (1) in mice, loss of NPC1 function reduces hepatocyte TG content and secretion by increasing the metabolic flux of carbons into cholesterol synthesis; and (2) common variation in\n            <jats:italic>NPC1<\/jats:italic>\n            contributes to serum TG levels in humans.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.110.207191","type":"journal-article","created":{"date-parts":[[2010,5,21]],"date-time":"2010-05-21T02:46:20Z","timestamp":1274409980000},"page":"1614-1620","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Niemann-Pick C1 Modulates Hepatic Triglyceride Metabolism and Its Genetic Variation Contributes to Serum Triglyceride Levels"],"prefix":"10.1161","volume":"30","author":[{"given":"Riikka-Liisa","family":"Uronen","sequence":"first","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Lundmark","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marju","family":"Orho-Melander","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Jauhiainen","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Larsson","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Siegbahn","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Wallentin","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjo\u0308rn","family":"Zethelius","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olle","family":"Melander","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Christine","family":"Syva\u0308nen","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Ikonen","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine\/Anatomy, University of Helsinki, Helsinki, Finland (R.-L.U., and E.I.); Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden (P.L., K.L., and A.-C.S.); the Department of Clinical Sciences in Malmo\u0308 (M.O.-M.), Diabetes and Endocrinology Research Unit, Lund University, Malmo\u0308, Sweden; the Institute of Health and Welfare (M.J.), Helsinki, Finland; the Department of Medical Sciences (A.S.), Clinical Chemistry, Uppsala University; the..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","unstructured":"Patterson MC Vanier MT Suzuki K Morris JA Carstea ED Neufeld EB Blanchette-Mackie EJ Pentchev PG. 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