Diabetes & Metabolism Journal

Original Articles

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; Korean Diabetes J. 2006;30(5):324-335. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.324

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BACKGROUND
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.

Citations

Citations to this article as recorded by

Beneficial effect of Combination with Korean Red Ginseng and Morus alba in metabolic syndrome
Yun Jung Lee, Hye Yoom Kim, Jung Joo Yoon, So Min Lee, You Mee Ahn, Joung Hyun Kho, Min Chul Kho, Ho Sub Lee, Kyung Min Choi, Dae Gill Kang
The Korea Journal of Herbology.2012; 27(6): 99. CrossRef
Effects of Mixed Extract from Lycium chinense, Cordyceps militaris, and Acanthopanax senticosus on Glucose-Regulating Enzymes of HepG2 in Hyperglycemic Conditions
Dae-Jung Kim, Jeong-Mi Kim, Tae-Hyuk Kim, Jong-Mi Baek, Hyun-Sook Kim, Myeon Choe
Journal of the Korean Society of Food Science and Nutrition.2010; 39(9): 1257. CrossRef

Regulation of mFABP (fatty acid binding protein) Expression by PPAR in Cultured Human Skeletal Muscle Cell.: Hyeosn Jeong Jeon, Won Shik Shinn, Jeong Mi Kim, Hye Kyung Hong, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2000;24(4):413-420. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Fatty acid binding protein (FABP), putative mammalian fatty acid transporter, plays a role in fatty acid transport, the modulation of cellular signal transduction pathways and the protection against detergent like effects of fatty acids. FABP found in liver, adipose tissue, heart, skeletal muscle and FABP in skeletal muscle accounts for 2% of total protein mass. FABP expression has shown to be up-regulated by PPAR in liver and adipocyte. Adipocyte and liver FABP genes have a functional PPRE (PPAR responsive element) in their promoter region. This evidence led us to investigate for a possible the regulation of mFABP expression by PPAR in cultured human skeletal muscle cell. METHODS: Myoblast were cultured in SkGM for 4weeks and were differentiated into myocyte in MEM for 4days. The myocytes were treated with PPAR ligand (troglitazone: 5 g/mL) or transduction with adenovirus-PPAR 1 (Ad-PPAR 1). mFABP expression was identified by northern blot. RESULTS: mFABP expression was up-regulated by 4.0+/-1.2 fold in the PPAR ligand (p<0.05). There was increased in mFABP expression with transduction with adenovirus-PPAR 1 while there was no change in mFABP expression which transducted with adenovirus - -galactosidase. CONCLUSION: These results demonstrates that mFABP expression is up-regulated by both PPAR ligand and by PPAR 1 over expression in cultured human skeletal muscle cells.

Metabolic Phenotype of Glycogen Synthase Gene Inhibition in Human Skeletal Muscle Cells.: Jae Joon Koh, Kyong Soo Park, Jeong Mi Kim, Seong Yeon Kim, Hong Kyu Lee, Theodore P Ciaraldi, Robert R Henry; Korean Diabetes J. 2000;24(3):331-339. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Glycogen synthase (GS) is the rate-limiting enzyme controlling non-oxidative glucose disposal in skeletal muscle. Reduction in GS activity and impaired insulin responsiveness are characteristic features of skeletal muscle in type 2 diabetes that contribute to glucose intolerance. These properties also exist in human skeletal muscle cell cultures from type 2 diabetic subjects. The aim of study is to determine the effect of an isolated reduction in GS on glucose metabolism and if this change can generate a diabetes-like state. METHODS: Cultured skeletal muscle cells from non-diabetic subjects were treated with antisense oligodeoxynucleotides (ODN) to GS to interfere with expression of the gene for 6 days. GS activity, protein expression, glycogen synthesis and cellular glycogen content were measured. RESULTS: Treatment with antisense ODN reduced GS protein expression by 70% compared to control (scrambled) ODN (p<0.01). Both total GS activity and that measured at 0.1 mM G-6-P were reduced by antisense ODN treatment. Insulin responsiveness of GS was also halved. Basal GS FV0.1 was decreased in both antisense ODN and control ODN treated cells and antisense treated cells did not show increase in GS FV0.1 in response to insulin stimulation. Glucose incorporation into glycogen under basal conditions was unaltered after antisense ODN treatment, though no further stimulation in response to insulin was observed. Yet both cellular glycogen content and glycogen synthesis were lower in antisense ODN treated cells compared to control ODN treated cells. CONCLUSIONS: Reduction in GS expression in human skeletal muscle cell impair GS activity and insulin responsiveness but does not replicate the abnormalities of glycogen synthesis found in cultured diabetic skeletal muscle cells.

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