Sökning: id:"swepub:oai:lup.lub.lu.se:477b0776-1be4-4bd1-838a-1ac86cbfd315" >
Niemann-Pick C1 Mod...
Niemann-Pick C1 Modulates Hepatic Triglyceride Metabolism and Its Genetic Variation Contributes to Serum Triglyceride Levels
-
Uronen, Riikka-Liisa (författare)
-
- Lundmark, Per (författare)
- Uppsala universitet,Molekylär medicin
-
- Orho-Melander, Marju (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
-
visa fler...
-
Jauhiainen, Matti (författare)
-
- Larsson, Kristina (författare)
- Uppsala universitet,Molekylär medicin
-
- Siegbahn, Agneta (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Koagulation
-
- Wallentin, Lars (författare)
- Uppsala universitet,Klinisk kemi
-
- Zethelius, Björn (författare)
- Uppsala universitet,Geriatrik
-
- Melander, Olle (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
-
- Syvänen, Ann-Christine (författare)
- Uppsala universitet,Molekylär medicin
-
Ikonen, Elina (författare)
-
visa färre...
-
(creator_code:org_t)
- 2010
- 2010
- Engelska.
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636 .- 1079-5642. ; 30:8, s. 230-1614
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.)
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- lysosomal storage disease
- lipid droplets
- dyslipidemia
- fatty liver
- single-nucleotide polymorphism
- MEDICINE
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Uronen, Riikka-L ...
-
Lundmark, Per
-
Orho-Melander, M ...
-
Jauhiainen, Matt ...
-
Larsson, Kristin ...
-
Siegbahn, Agneta
-
visa fler...
-
Wallentin, Lars
-
Zethelius, Björn
-
Melander, Olle
-
Syvänen, Ann-Chr ...
-
Ikonen, Elina
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Kardiologi
- Artiklar i publikationen
-
Arteriosclerosis ...
- Av lärosätet
-
Lunds universitet
-
Uppsala universitet