RT Journal Article
T1 Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities
A1 Opazo-Ríos, Lucas
A1 Mas, Sebastián
A1 Marín-Royo, Gema
A1 Mezzano, Sergio
A1 Gómez-Guerrero, Carmen
A1 Moreno, Juan Antonio
A1 Egido, Jesús
K1 Lipotoxicity
K1 Obesity
K1 Type 2 diabetes
K1 Fatty kidney
K1 Diabetic nephropathy
K1 Chronic kidney disease
K1 Obesidad
K1 Diabetes mellitus tipo 2
K1 Ácidos grasos
K1 Riñón
K1 Nefropatías diabéticas
K1 Insuficiencia renal crónica
AB 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.
PB MDPI
YR 2020
FD 2020-04-10
LK http://hdl.handle.net/10668/3610
UL http://hdl.handle.net/10668/3610
LA en
NO Opazo-Ríos L, Mas S, Marín-Royo G, Mezzano S, Gómez-Guerrero C, Moreno JA, et al. Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities. Int J Mol Sci. 2020 Apr 10;21(7):2632
DS RISalud
RD Apr 17, 2025