Journal
METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 63, Issue 5, Pages 716-726Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2014.02.010
Keywords
Lipotoxicity; Diabetes; Proximal tubular epithelial cells; beta-oxidation; Epithelial to mesenchymal transition
Categories
Funding
- Shandong Provincial Hospital
- National Natural Science Foundation of China [81200610]
- Shandong Natural Science Foundation [ZR2009CM043]
- Shandong Doctoral Foundation of China [BS2009YY020]
- Shandong Science and Technology Developing Project [2009GG20002087]
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Objective. The study investigated the relationship between epithelial-to-mesenchymal transition (EMT) and lipotoxicity in diabetic nephropathy as well as the protective effect of acetyl-CoA carboxylase 2 (ACC2) silence. Methods. High glucose (30 mmol/L) cultured human proximal tubular epithelial cells (HK-2 cells) were used. Triglyceride content, fatty acid beta-oxidation rate, malonyl CoA content, and marker proteins of EMT, including E-cadherin (E-cad), alpha-smooth muscle actin (alpha-SMA) and transforming grow factor-beta (TGF-beta), were assessed. Silence of ACC2 was achieved by ACC2-shRNA lentivirus transfection. Results. In cultured human proximal tubular cells, high glucose induced fatty acid deposit before phenotypical and morphological changes of EMT. At 48 h, more triglyceride content, more malonyl CoA content and lower fatty acid beta-oxidation rate were detected. However, increased expression of TGF-beta, accompanied by loss of E-cad and acquisition of alpha-SMA, was observed at 98 h but not at 48 h. The silence of ACC2 in HK-2 cells led to restored cell morphology with less lipid deposition and less malonyl-CoA content, which resulted from faster p-oxidation rate. Conclusion. The progress of lipotoxicity participates in the development of diabetic nephropathy in early stage before EMT. The manipulation of lipid metabolism might act as a promising therapeutic intervention for diabetic nephropathy. (C) 2014 Elsevier Inc. All rights reserved.
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