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Int. J. Mol. Sci. 2016, 17(11), 1868; doi:10.3390/ijms17111868

Stearoyl-CoA Desaturase-1 Protects Cells against Lipotoxicity-Mediated Apoptosis in Proximal Tubular Cells

Department of Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan
Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Authors to whom correspondence should be addressed.
Academic Editors: Lu Cai, Yuehui Wang and Zhiguo Zhang
Received: 12 September 2016 / Revised: 31 October 2016 / Accepted: 3 November 2016 / Published: 9 November 2016
(This article belongs to the Special Issue Diabetic Complications: Pathophysiology, Mechanisms, and Therapies)
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Saturated 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
Keywords: lipotoxicity; desaturation; free fatty acid; proximal tubular epithelial cells; lipid droplet lipotoxicity; desaturation; free fatty acid; proximal tubular epithelial cells; lipid droplet

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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.

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