2007 Fiscal Year Final Research Report Summary
Molecular Analyses of Metabolic Abnormalities in PDIP-1 Null Mice
| Project/Area Number |
18590975
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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 | Gunma University |
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Principal Investigator |
SATOH Tetsurou Gunma University, Medicine and Molecular Science, Assistant Professor (40302484)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZUKA Takahiro Gunma University, Medicine and Molecular Science, Faculty (80400779)
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| Project Period (FY) |
2006 – 2007
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| Keywords | PPARγ / PDIP1 / transcriptional cofactor / metabolic syndrome / high-fat diet-induced obesity / fatty liver / fatty acid β oxidation |
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| Research Abstract |
Nuclear receptor PPARγ is the master regulator of adipocyte differentiation and facilitates lipid reserve in a body. Using yeast two-hybrid screen, we recently isolated a novel coactivator of PPARγ, PDIP1 also known as PRIC285. To elucidate physiological function of PDIP1, mice lacking PDIP1 were generated using homologous recombination. Brown adipose tissues in PDIP1-/- mice revealed inappropriate phenotype containing larger fat droplets with reduced expression of uncoupling protein-1 (UCP-1), aP2 and calnitin palmitoyle transferase-la genes. Although white adipose tissues (WAT) appeared morphologically normal, serum triglyceride and very low density lipoprotein in PDIP1^<-/-> mice were significantly decreased. Causatively, expression of a subset of genes enhancing fatty-acid oxidation in liver and WAT were significantly upregulated. When fed a high-fat diet (HFD), PDIP1^<-/-> mice showed resistance to obesity with reduced adiposity and hepatic steatosis and improved glucose and insulin tolerance. These findings suggest that PDIP1 is deleteriously involved in development of HFD-induced obesity and dyslipidemia, thus representing a potential target treating for metabolic syndrome with lipotoxicity.
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