Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities

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 li...

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Autores: Opazo-Ríos, Lucas, Mas, Sebastián, Marín-Royo, Gema, Mezzano, Sergio, Gómez Guerrero, Carmen, Moreno, Juan Antonio, Egido de los Ríos, Jesús
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/693449
Acceso en línea:http://hdl.handle.net/10486/693449
https://dx.doi.org/10.3390/ijms21072632
Access Level:acceso abierto
Palabra clave:Chronic kidney disease
Diabetic nephropathy
Fatty kidney
Lipotoxicity
Obesity
Type 2 diabetes
Medicina
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spelling Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunitiesOpazo-Ríos, LucasMas, SebastiánMarín-Royo, GemaMezzano, SergioGómez Guerrero, CarmenMoreno, Juan AntonioEgido de los Ríos, JesúsChronic kidney diseaseDiabetic nephropathyFatty kidneyLipotoxicityObesityType 2 diabetesMedicinaLipotoxicity 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.The authors’ work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495, and SAF2015-63696-R), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, and RYC-2017-22369), Fondecyt Project (No. 1160465), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), and Spanish Society of Atherosclerosis (SEA).MDPI, Basel, SMwitzerlandDepartamento de MedicinaFacultad de MedicinaInstituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)20202020-04-10research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/693449https://dx.doi.org/10.3390/ijms21072632reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6934492026-06-23T12:46:27Z
dc.title.none.fl_str_mv Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
title Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
spellingShingle Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
Opazo-Ríos, Lucas
Chronic kidney disease
Diabetic nephropathy
Fatty kidney
Lipotoxicity
Obesity
Type 2 diabetes
Medicina
title_short Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
title_full Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
title_fullStr Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
title_full_unstemmed Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
title_sort Lipotoxicity and diabetic nephropathy: Novel mechanistic insights and therapeutic opportunities
dc.creator.none.fl_str_mv Opazo-Ríos, Lucas
Mas, Sebastián
Marín-Royo, Gema
Mezzano, Sergio
Gómez Guerrero, Carmen
Moreno, Juan Antonio
Egido de los Ríos, Jesús
author Opazo-Ríos, Lucas
author_facet Opazo-Ríos, Lucas
Mas, Sebastián
Marín-Royo, Gema
Mezzano, Sergio
Gómez Guerrero, Carmen
Moreno, Juan Antonio
Egido de los Ríos, Jesús
author_role author
author2 Mas, Sebastián
Marín-Royo, Gema
Mezzano, Sergio
Gómez Guerrero, Carmen
Moreno, Juan Antonio
Egido de los Ríos, Jesús
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
dc.subject.none.fl_str_mv Chronic kidney disease
Diabetic nephropathy
Fatty kidney
Lipotoxicity
Obesity
Type 2 diabetes
Medicina
topic Chronic kidney disease
Diabetic nephropathy
Fatty kidney
Lipotoxicity
Obesity
Type 2 diabetes
Medicina
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-04-10
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/693449
https://dx.doi.org/10.3390/ijms21072632
url http://hdl.handle.net/10486/693449
https://dx.doi.org/10.3390/ijms21072632
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI, Basel, SMwitzerland
publisher.none.fl_str_mv MDPI, Basel, SMwitzerland
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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