2013 Fiscal Year Final Research Report
Studies on molecular mechanisms of PPARalpha-independent triglyceride-lowering effects of fibrate drugs
| Project/Area Number |
23790178
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | 脂質代謝 / 脂肪酸代謝 / ミトコンドリアβ酸化 / 臨床用量 |
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| Research Abstract |
This study examined the effects of clinically relevant low doses of fibrate drugs on hepatic lipid metabolism in mice having diet-induced hepatosteatosis. Low-dose fibrates reduced steatosis through an enhancement of hepatic mitochondrial fatty acid beta-oxidation function, which was not due to known PPARalpha activation. This novel pharmacologic action seemed to be associated with increased protein stability of beta-oxidation enzymes, and this was possibly due to increased contents of cardiolipin, a mitochondria-specific phospholipid important in stability/functionality of mitochondrial proteins. These effects were not accompanied by non-physiological phenomena such as hepatomegaly. Thus, these findings may be useful for better understanding fibrate action in humans.
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