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Sökning: WFRF:(Melander Björn) > Niemann-Pick C1 Mod...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004427naa a2200505 4500
001oai:lup.lub.lu.se:477b0776-1be4-4bd1-838a-1ac86cbfd315
003SwePub
008160401s2010 | |||||||||||000 ||eng|
009oai:DiVA.org:uu-130558
0247 a https://lup.lub.lu.se/record/16577002 URI
0247 a https://doi.org/10.1161/ATVBAHA.110.2071912 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1305582 URI
040 a (SwePub)lud (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Uronen, Riikka-Liisa4 aut
2451 0a Niemann-Pick C1 Modulates Hepatic Triglyceride Metabolism and Its Genetic Variation Contributes to Serum Triglyceride Levels
264 1c 2010
520 a Objective-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. 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-3] oleic acid and [H-3] acetate into TG was decreased, but shunting of oleic acid- or acetate-derived [H-3] carbons into cholesterol was increased. Inhibition of cholesterol synthesis normalized TG synthesis, content, and secretion in Npc1(-/-) 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 NPC1 single-nucleotide polymorphisms in a cohort of 1053 men, with the lowest P=8.7 x 10(-4) for the single-nucleotide polymorphism rs1429934. The association between the rs1429934 A allele and higher TG levels was replicated in 2 additional cohorts, which included 8041 individuals. Conclusion-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 NPC1 contributes to serum TG levels in humans. (Arterioscler Thromb Vasc Biol. 2010;30:1614-1620.)
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653 a lysosomal storage disease
653 a lipid droplets
653 a dyslipidemia
653 a fatty liver
653 a single-nucleotide polymorphism
653 a MEDICINE
7001 a Lundmark, Peru Uppsala universitet,Molekylär medicin4 aut0 (Swepub:uu)pelun425
7001 a Orho-Melander, Marjuu Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups4 aut0 (Swepub:lu)endo-mor
7001 a Jauhiainen, Matti4 aut
7001 a Larsson, Kristinau Uppsala universitet,Molekylär medicin4 aut
7001 a Siegbahn, Agnetau Uppsala universitet,Institutionen för medicinska vetenskaper,Koagulation4 aut0 (Swepub:uu)agsie424
7001 a Wallentin, Larsu Uppsala universitet,Klinisk kemi4 aut0 (Swepub:uu)larswall
7001 a Zethelius, Björnu Uppsala universitet,Geriatrik4 aut0 (Swepub:uu)bjorzeth
7001 a Melander, Olleu Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups4 aut0 (Swepub:lu)endo-ome
7001 a Syvänen, Ann-Christineu Uppsala universitet,Molekylär medicin4 aut0 (Swepub:uu)anncsyva
7001 a Ikonen, Elina4 aut
7102 a Uppsala universitetb Molekylär medicin4 org
7730 t Arteriosclerosis, Thrombosis and Vascular Biologyg 30:8, s. 230-1614q 30:8<230-1614x 1524-4636x 1079-5642
8564 u http://dx.doi.org/10.1161/ATVBAHA.110.207191x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/1657700
8564 8u https://doi.org/10.1161/ATVBAHA.110.207191
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-130558

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