Stearoyl-CoA Desaturase-1 Protects Cells against Lipotoxicity-Mediated Apoptosis in Proximal Tubular Cells
AbstractSaturated fatty acid (SFA)-related lipotoxicity is a pathogenesis of diabetes-related renal proximal tubular epithelial cell (PTEC) damage, closely associated with a progressive decline in renal function. This study was designed to identify a free fatty acid (FFA) metabolism-related enzyme that can protect PTECs from SFA-related lipotoxicity. Among several enzymes involved in FFA metabolism, we identified stearoyl-CoA desaturase-1 (SCD1), whose expression level significantly decreased in the kidneys of high-fat diet (HFD)-induced diabetic mice, compared with non-diabetic mice. SCD1 is an enzyme that desaturates SFAs, converting them to monounsaturated fatty acids (MUFAs), leading to the formation of neutral lipid droplets. In culture, retrovirus-mediated overexpression of SCD1 or MUFA treatment significantly ameliorated SFA-induced apoptosis in PTECs by enhancing intracellular lipid droplet formation. In contrast, siRNA against SCD1 exacerbated the apoptosis. Both overexpression of SCD1 and MUFA treatment reduced SFA-induced apoptosis via reducing endoplasmic reticulum stress in cultured PTECs. Thus, HFD-induced decrease in renal SCD1 expression may play a pathogenic role in lipotoxicity-induced renal injury, and enhancing SCD1-mediated desaturation of SFA and subsequent formation of neutral lipid droplets may become a promising therapeutic target to reduce SFA-induced lipotoxicity. The present study provides a novel insight into lipotoxicity in the pathogenesis of diabetic nephropathy. View Full-Text
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Iwai, T.; Kume, S.; Chin-Kanasaki, M.; Kuwagata, S.; Araki, H.; Takeda, N.; Sugaya, T.; Uzu, T.; Maegawa, H.; Araki, S.-I. Stearoyl-CoA Desaturase-1 Protects Cells against Lipotoxicity-Mediated Apoptosis in Proximal Tubular Cells. Int. J. Mol. Sci. 2016, 17, 1868.
Iwai T, Kume S, Chin-Kanasaki M, Kuwagata S, Araki H, Takeda N, Sugaya T, Uzu T, Maegawa H, Araki S-I. Stearoyl-CoA Desaturase-1 Protects Cells against Lipotoxicity-Mediated Apoptosis in Proximal Tubular Cells. International Journal of Molecular Sciences. 2016; 17(11):1868.Chicago/Turabian Style
Iwai, Tamaki; Kume, Shinji; Chin-Kanasaki, Masami; Kuwagata, Shogo; Araki, Hisazumi; Takeda, Naoko; Sugaya, Takeshi; Uzu, Takashi; Maegawa, Hiroshi; Araki, Shin-ichi. 2016. "Stearoyl-CoA Desaturase-1 Protects Cells against Lipotoxicity-Mediated Apoptosis in Proximal Tubular Cells." Int. J. Mol. Sci. 17, no. 11: 1868.
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