| Project/Area Number |
21K20870
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
Chang Jiuyang 大阪大学, 大学院医学系研究科, 招へい研究員 (60907707)
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| Project Period (FY) |
2021-08-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 心筋症 / 7-ケトコレステロール / 脂肪肝炎 / 糖尿病 / 7-ketocholesterol / steatohepatitis / cardiac dysfunction / diabetes / cardomyopathy / oxysterol / NAFLD / cardiomyopathy / inflammation |
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| Outline of Research at the Start |
It has been demonstrated that CVD including atherosclerosis and heart failure is the leading cause of mortality among patients with Non-alcoholic fatty liver disease (NAFLD). However, the genetic background which induces both NAFLD and CVD is still unclear. We have focused on a dietary factor, oxysterol in processed foods, and demonstrated that oxysterol accelerated hepatic lipid accumulation and inflammation in obese mice. In this study, I hypothesize that dietary oxysterol might induce cardiomyopathy with steatohepatitis.
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| Outline of Final Research Achievements |
C57Bl/6 mice were injected STZ (160mg/kg) intraperitoneally and confirmed that the blood glucose levels were in the range of 200-350 mg/dL two weeks after injection. Diabetic mice were fed high fat diet with or without 7KC for four or twelve weeks and sacrificed. In STZ-induced diabetic mice, oil Red O staining showed more and larger lipid droplets in WD+-KC. Lipid extraction analysis has demonstrated that triglycerides and free cholesterol were significantly increased in liver in WD+7KC group. Serum ALT and TNF-a were significantly increased in WD+7KC and F4/80 staining exhibited increased macrophages in WD+7KC. Pathway analysis by RNA sequencing demonstrated that several pathways, such as TNF signaling pathway were upregulated in WD+7KC. Importantly, in heart, inflammatory cytokine, IL-1b was upregulated in WD+7KC. In summary, dietary supplementation of 7KC accelerated cardiac inflammation through hepatic steatosis, inflammatory cell infiltration and fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
It has been demonstrated that cardiovascular disease is the leading cause of mortality among patients with non-alcoholic fatty liver diseases. We have demonstrated that 7KC in diet might accelerate cardiac inflammation through hepatic steatosis and inflammation by NLRP3 inflammasome activation.
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