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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

1
Department of Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan
2
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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Abstract

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
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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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