Diabetes Metab J > Volume 30(5); 2006 > Article
Korean Diabetes Journal 2006;30(5):324-335.
DOI: https://doi.org/10.4093/jkda.2006.30.5.324    Published online September 1, 2006.
Effects of PPAR-alpha and-gamma Agonists on Fatty Acid Metabolism of Muscle Cells in Hyperlipidemic and Hyperglycemic Conditions.
Yong jik Lee, Zheng Shan Zhao, Soo Kyung Kim, Hae Jin Kim, Wan Sub Shim, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha
1Yonsei University Brain Korea 21 Project for Medical Science, Korea.
2Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Korea.
3Department of Internal Medicine, Inha University College of Medicine, Korea.
4Department of Internal Medicine, College of Medicine, Pochon CHA University, Korea.
5Department of Endocrinology and Metabolism, Ajou Univerisity School of Medicine, Korea.
6Division of clinical research, Affiliated Research Institute, Seoul Medical Center, Korea.
Studies for the regulation of fatty acid metabolism are deficient relatively in skeletal muscle and heart. The investigations in pathological conditions for malonyl-CoA decarboxylase (MCD) and for the relation of MCD and PPAR-alpha.-gamma agonists are insufficient in particular. METHODS: In the current study, fully differentiated H9c2 muscle cells were exposed to pathological conditions such as hyperlipidemic (0.1 mM Palmitate) and hyperglycemic (16.5 mM Glucose) condition with 5 uM PPAR-gamma agonist (rosiglitazone) and 10 uM PPAR-alpha agonist (WY14,643) and then experiments such as MCD activity assay, MCD real-time RT-PCR, MCD reporter gene assay, MCD Western blotting, PPAR-alpha Western blotting, and palmitate oxidation test were carried out. RESULTS: Only PPAR-alpha agonist increased MCD activity. In the result of real-time RT-PCR, both PPAR-alpha and PPAR-gamma agonists elevated MCD mRNA expression in hyperlipidemic condition. MCD protein expression was decreased in hyperlipidemic condition, however, increased in rosiglitazone, or WY14,643 treated conditions. Rosiglitazone, and WY14,643 treated groups showed incresed MCD protein expression in hyperglycemic condition. Hyperlipidemic control group and PPAR-alpha.-gamma agonists treated groups presented about 3.8 times more increased palmitate oxidation level than normolipidemic control group in hyperlipidemic condition. PPAR-alpha agonist treated group showed 49% more increased palmitate oxidation rate than hyperlipidemic control group in primary cultured rat skeletal muscle cells. The amount of palmitate oxidation from differentiated H9c2 muscle cells that had overexpressed PPAR-alpha structural genes was more increased than control group. CONCLUSION: This study suggests that PPAR-alpha agonist ameliorates the defects induced by hyperlipidemic condition through the regulation of MCD. In summary, a closely reciprocal relation among PPAR-alpha agonist, MCD, and fatty acid oxidation existed distinctly in hyperlipidemic condition, but not in hyperglycemic condition.
Key Words: Fatty acid oxidation, Hyperglycemic, Hyperlipidemic, H9c2 cell, Malonyl-CoA decarboxylase (MCD), PPAR-alpha agonist, PPAR-gamma agonist

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