Establishment of an animal model for muscle-specific overexpression of peroxisome proliferator-activated receptor (PPAR) δ and analysis of the effect of skeletal muscle PPAR δ on exercise tolerance and glucose metabolism
| Project/Area Number |
17500414
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Sports science
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
SUZUKI Hiroaki (2006) University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院人間総合科学研究科, 講師 (40344890)
飯田 薫子 (2005) 筑波大学, 大学院・人間総合科学研究科, 講師 (50375458)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOYOSHIMA Hideo Jichi Medical University, Division of General Medicine, Associate Professor, 大宮医療センター総合医学I, 助教授 (20197966)
YAMADA Nobuhiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院人間総合科学研究科, 教授 (40200729)
鈴木 浩明 筑波大学, 大学院・人間総合科学研究科, 講師 (40344890)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | skeletal muscle / PPARδ / exercise tolerance / diabetes mellitus / 有酸素運動 / 糖代謝 / 脂質代謝 / PPARdelta / 遺伝子改変 |
|---|
| Research Abstract |
Insulin resistance and decreased secretion of insulin are associated with development of type 2 diabetes. Skeletal muscle is a major contributor of insulin resistance. To investigate the specific functions of PPARδ in skeletal muscle development, exercise tolerance, and glucose and lipid metabolism, we generated mouse lines harboring a transgene consisting of VP 16-PPARδ fusion cDNA under the control of the human α-skeletal actin promoter. We confirmed that the VP 16-PPARδ fusion protein up-regulates both acyl-CoA oxidase and HMG CoA synthase promoter activities. The transgene was injected into C57BL/6 or KK/Ta zygotes. KK/Ta mice are model of type 2 diabetes. We obtained only two lines of KK/Ta transgenics which expressed the transgenic RNA and protein in skeletal muscle. No significant effects of PPARδ overexpression on weight, running endurance, or glycemic control.
Adiponectin is an adipocyte-derived protein that plays a pivotal role in lipid and glucose metabolism. Recently, two ty
… More
pes of adiponectin receptors (AdipoR1 and AdipoR2) were identified. We investigated whether exercise training (ET) or dietary restriction (DR) affects the expression of adiponectin receptors in skeletal muscle and liver, thereby improving glucose and lipid metabolism in KKAy mice. KKAy mice were subjected to 8 weeks of exercise training or food restriction. Both the 8-week exercise training and food restriction protocol improved insulin resistance in KKAy mice but did not alter plasma adiponectin concentration nor its mRNA expression. In comparison with C57BL/6 mice, AdipoR1 expression level was significantly decreased in skeletal muscle and AdipoR2 expression level was significantly increased in the liver in KKAy mice. After the 8-week experimental protocol, the expression level of AdipoR1 mRNA was approximately 1.8-fold greater in the skeletal muscle and 1.3-fold treater in the liver, and the level of AdipoR2 mRNA was 30% less in the liver of the ET group as compared with the control group. These findings suggest that chronic exercise training affects the expression level of adiponectin receptors thereby improving insulin resistance in KKAy mice. Less
|
Report
(3 results)
Research Products
(5 results)
