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Tissue-specific regulation of malonyl-CoA decarboxylase activity in OLETF rats

 H. J. Kim  ;  Z. S. Zhao  ;  Y. J. Lee  ;  W. S. Shim  ;  S. K. Kim  ;  C. W. Ahn  ;  C. W. Park  ;  H. C. Lee  ;  B. S. Cha 
 DIABETES OBESITY & METABOLISM, Vol.8(2) : 175-183, 2006 
Journal Title
Issue Date
Animals ; Body Weight ; Carboxy-Lyases/metabolism* ; Cholesterol/blood ; Fasting/blood ; Fatty Acids, Nonesterified/metabolism ; Glucose/metabolism ; Hypoglycemic Agents/pharmacology* ; Insulin/metabolism ; Male ; Metformin/pharmacology* ; Muscle, Skeletal/enzymology ; Myocardium/metabolism ; Pioglitazone ; RNA, Messenger/metabolism ; Rats ; Rats, Inbred OLETF ; Thiazolidinediones/pharmacology* ; Triglycerides/metabolism
AIM: The intracellular concentration of malonyl-CoA, a key regulator of fatty acid oxidation, is determined both from its synthesis by acetyl-CoA carboxylase and from its degradation by malonyl-CoA decarboxylase (MCD). The aim of our study was to investigate the activity and mRNA expression of MCD under insulin resistance and after treatment with insulin sensitizers in different tissues. METHODS: We treated 18-week Otusuka Long-Evans Tokushima Fatty (OLETF) rats with pioglitazone (10 mg/kg/day) or metformin (300 mg/kg/day) for 8 weeks and determined the activity and mRNA expression of MCD in diabetic OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats in myocardial and skeletal muscles, and in liver. RESULTS: The MCD activities of myocardial and skeletal muscles were remarkably reduced in OLETF rats compared with LETO rats (995 +/- 114 vs. 2012 +/- 359, 58 +/- 11 vs. 167 +/- 40 pmol/min/mg protein; p = 0.005 and p = 0.010). Surprisingly, after pioglitazone treatment, not after metformin, the MCD activities of myocardial and skeletal muscles (1906 +/- 320 and 259 +/- 44 pmol/min/mg protein) increased up to the levels in LETO rats. MCD mRNA expression in OLETF rats was also reduced in myocardial and skeletal muscles vs. LETO rats (p = 0.049 and p = 0.008) and was unchanged by pioglitazone or metformin treatment. In the liver, MCD activity and mRNA expression were similar in OLETF and LETO rats. CONCLUSION: Pioglitazone treatment restored MCD activity to non-diabetic level and improved the restrained fatty acid metabolism in myocardial and skeletal muscles caused by insulin-resistant diabetic status.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Chul Woo(안철우) ORCID logo https://orcid.org/0000-0003-3733-7486
Lee, Hyun Chul(이현철)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
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