2002 Fiscal Year Final Research Report Summary
Studies on a model animal for atherogenic lipoproteins and atherosclerosis
| Project/Area Number |
13671172
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SHIMAO Hitoshi University of Tsukuba, Clinical Medicine, Assist. Prof., 臨床医学系, 講師 (20251241)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Akimitsu University of Tsukuba, Clinical Medicine, Assist. Prof., 臨床医学系, 助手 (70344893)
SONE Hrohito University of Tsukuba, Clinical Medicine, Assist. Prof., 臨床医学系, 講師 (30312846)
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| Project Period (FY) |
2001 – 2002
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| Keywords | atherosclerosis / lipoproteins / remnant lipoproteins / LDL / mice / triglycerides / SREBO / SREBP |
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| Research Abstract |
To investigate effects of enhanced hepatic trigylcerides synthesis on production of atherogenic lipoproteins, SREBP-lc transgeni and LDL receptor-deficient doubly mutant mice (BP1c/LDLRKO). were generated and their plasma lipoproteins were studied BP1c/LDLRKO showed incrases in plasma triglycerides and cholesterol especially at feeding. On agarose electrophoresis, broa beta band, suggesting presence of remnant lipoproteins was increased and LIDL cholesterol was inversely decreased as compared to controls of LDLR KO mice. Northern blot analysis of livers showed that over-expression of SREBP-lc induced expression of lipogenic enzyme genes such as FAS, ACC, and SCO. Activation of lipogenic gene expression could incrase hepatic postprandia synthesis of triglycerides and production of TG rich lipoproteins, which were accumulated in the absence of LDLR converting to remnant lipoproteins in plasma. Due to the accumulation of these atherogenic lipoproteins, BP1c/LDLRKO exhibited atherorm formation around aortic sinus at age of 8 months even on a regular diet. These mice are a good model for postprandial hyperlipidemia and metabolic syndrome.
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