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Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

1
Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain
2
Laboratorio de Nefrología, Facultad de Medicina, Universidad Austral de Chile, 5090000 Valdivia, Chile
3
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
4
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, 14004 Cordoba, Spain
5
Hospital Universitario Reina Sofía, 14004 Cordoba, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(7), 2632; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072632
Received: 12 March 2020 / Revised: 7 April 2020 / Accepted: 8 April 2020 / Published: 10 April 2020
(This article belongs to the Special Issue Molecular Mechanisms Involved in Diabetic Nephropathy)
Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Serum lipid abnormalities and renal ectopic lipid accumulation have been associated with the development of kidney diseases, in particular diabetic nephropathy. Chronic hyperinsulinemia, often seen in type 2 diabetes, plays a crucial role in blood and liver lipid metabolism abnormalities, thus resulting in increased non-esterified fatty acids (NEFA). Excessive lipid accumulation alters cellular homeostasis and activates lipogenic and glycogenic cell-signaling pathways. Recent evidences indicate that both quantity and quality of lipids are involved in renal damage associated to lipotoxicity by activating inflammation, oxidative stress, mitochondrial dysfunction, and cell-death. The pathological effects of lipotoxicity have been observed in renal cells, thus promoting podocyte injury, tubular damage, mesangial proliferation, endothelial activation, and formation of macrophage-derived foam cells. Therefore, this review examines the recent preclinical and clinical research about the potentially harmful effects of lipids in the kidney, metabolic markers associated with these mechanisms, major signaling pathways affected, the causes of excessive lipid accumulation, and the types of lipids involved, as well as offers a comprehensive update of therapeutic strategies targeting lipotoxicity. View Full-Text
Keywords: lipotoxicity; obesity; type 2 diabetes; fatty kidney; diabetic nephropathy; chronic kidney disease lipotoxicity; obesity; type 2 diabetes; fatty kidney; diabetic nephropathy; chronic kidney disease
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MDPI and ACS Style

Opazo-Ríos, L.; Mas, S.; Marín-Royo, G.; Mezzano, S.; Gómez-Guerrero, C.; Moreno, J.A.; Egido, J. Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities. Int. J. Mol. Sci. 2020, 21, 2632. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072632

AMA Style

Opazo-Ríos L, Mas S, Marín-Royo G, Mezzano S, Gómez-Guerrero C, Moreno JA, Egido J. Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities. International Journal of Molecular Sciences. 2020; 21(7):2632. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072632

Chicago/Turabian Style

Opazo-Ríos, Lucas; Mas, Sebastián; Marín-Royo, Gema; Mezzano, Sergio; Gómez-Guerrero, Carmen; Moreno, Juan A.; Egido, Jesús. 2020. "Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities" Int. J. Mol. Sci. 21, no. 7: 2632. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072632

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