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Impaired fatty acid metabolism in type 2 diabetic skeletal muscle cells is reversed by PPARγ agonists

Authors
 Bong-Soo Cha  ;  Theodore P. Ciaraldi  ;  Kyong-Soo Park  ;  Leslie Carter  ;  Sunder R. Mudaliar  ;  Robert R. Henry 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, Vol.289(1) : E151-E159, 2005 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 
ISSN
 0193-1849 
Issue Date
2005
MeSH
Adult ; Caprylates/metabolism* ; Cells, Cultured ; Chromans/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; Fatty Acids/metabolism ; Female ; Humans ; Lipid Metabolism* ; Male ; Middle Aged ; Myoblasts, Skeletal/drug effects ; Myoblasts, Skeletal/metabolism* ; Oxidation-Reduction/drug effects ; PPAR gamma/agonists* ; PPAR gamma/metabolism* ; Palmitates/metabolism* ; Thiazolidinediones/pharmacology* ; Troglitazone
Keywords
type 2 diabetes mellitus ; fatty acid oxidation ; thiazolidinediones ; mitochondria
Abstract
The impact of type 2 diabetes on the ability of muscle to accumulate and dispose of fatty acids and triglycerides was evaluated in cultured muscle cells from nondiabetic (ND) and type 2 diabetic (T2D) subjects. In the presence of 5 μM palmitate, T2D muscle cells accumulated less lipid than ND cells (11.5 ± 1.2 vs. 15.1 ± 1.4 nmol/mg protein, P < 0.05). Chronic treatment (4 days) with the peroxisome proliferator-activated receptor-γ (PPARγ) agonist troglitazone increased palmitate accumulation, normalizing uptake in T2D cells. There were no significant differences between groups with regard to the relative incorporation of palmitate into neutral lipid species. This distribution was also unaffected by troglitazone treatment. β-Oxidation of both long-chain (palmitate) and medium-chain (octanoate) fatty acids in T2D muscle cells was reduced by ∼40% compared with ND cells. Palmitate oxidation occurred primarily in mitochondrial (∼40–50% of total) and peroxisomal (20–30%) compartments. The diabetes-related defect in palmitate oxidation was localized to the mitochondrial component. Both palmitate and octanoate oxidation were stimulated by a series of thiazolidinediones. Oxidation in T2D muscle cells was normalized after treatment. Troglitazone increased the mitochondrial component of palmitate oxidation. Skeletal muscle cells from T2D subjects express defects in free fatty acid metabolism that are retained in vitro, most importantly defects in β-oxidation. These defects can be corrected by treatment with PPARγ agonists. Augmentation of fatty acid disposal in skeletal muscle, potentially reducing intramyocellular triglyceride content, may represent one mechanism for the lipid-lowering and insulin-sensitizing effects of thiazolidinediones.
Files in This Item:
T200501062.pdf Download
DOI
10.1152/ajpendo.00141.2004
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151195
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