2011 Fiscal Year Final Research Report
The relationship between lowered expression level of novel mitochondrial regulator-A and onset of diabetes mellitus
| Project/Area Number |
22790856
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Metabolomics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
MAEDA Shiro 独立行政法人理化学研究所, 内分泌・代謝疾患研究チーム (50314159)
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| Project Period (FY) |
2010 – 2011
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| Keywords | エネルギー / 糖質代謝異常 / ミトコンドリア機能 |
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| Research Abstract |
Recent studies reveal a strong relationship between reduced mitochondrial content and insulin resistance in human skeletal muscle, although the underlying factors responsible for this association remain unknown. To address this question, we analyzed muscle biopsy samples from young, lean, insulin resistant(IR) offspring of parents with type 2 diabetes and control subjects by microarray analyses and found significant differences in expression of～512 probe pairs. We then screened these genes for their potential involvement in the regulation of mitochondrial biogenesis using RNA interference and found that mRNA and protein expression of lipoprotein lipase(LPL) in skeletal muscle was significantly decreased in the IR offspring and was associated with decreased mitochondrial density. Then we screened single polynucreotide polymorphism in LPL promoter lesion and found that two SNP are a potentially associated with diabetes onset. However, we have repeated analysis of these SNP in GWAS, we found no significant relationship. Then, we observed that LPL knockdown decreased mitochondrial content by effectively decreasing fatty acid delivery and subsequent activation of peroxisome proliferator-activated receptor(PPAR)-δ. Taken together, these data suggest that decreased mitochondrial content in muscle of IR offspring may be due in part to reductions in LPL expression in skeletal muscle resulting in decreased PPAR-δactivation.
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Research Products
(12 results)
