title: Renal Lipotoxicity-Associated Inflammation and Insulin Resistance Affects Actin Cytoskeleton Organization in Podocytes.
abstract: In the last few decades a change in lifestyle has led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance (IR), dyslipidemia, type 2 diabetes and renal disease. The excess calories are stored as triglycerides in adipose tissue, but also may accumulate ectopically in other organs, including the kidney, which contributes to the damage through a toxic process named lipotoxicity. Recently, the evidence suggests that renal lipid accumulation leads to glomerular damage and, more specifically, produces dysfunction in podocytes, key cells that compose and maintain the glomerular filtration barrier. Our aim was to analyze the early mechanisms underlying the development of renal disease associated with the process of lipotoxicity in podocytes. Our results show that treatment of podocytes with palmitic acid produced intracellular accumulation of lipid droplets and abnormal glucose and lipid metabolism. This was accompanied by the development of inflammation, oxidative stress and endoplasmic reticulum stress and insulin resistance. We found specific rearrangements of the actin cytoskeleton and slit diaphragm proteins (Nephrin, P-Cadherin, Vimentin) associated with this insulin resistance in palmitic-treated podocytes. We conclude that lipotoxicity accelerates glomerular disease through lipid accumulation and inflammation. Moreover, saturated fatty acids specifically promote insulin resistance by disturbing the cytoarchitecture of podocytes. These data suggest that renal lipid metabolism and cytoskeleton rearrangements may serve as a target for specific therapies aimed at slowing the progression of podocyte failure during metabolic syndrome.
authors.affiliation: Departamento de Ciencias Básicas de la Salud, Área de Bioquímica y Genética Molecular. Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-García
authors.affiliation: Departamento de Ciencias Básicas de la Salud, Área de Bioquímica y Genética Molecular. Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, Madrid, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Izquierdo-Lahuerta
authors.affiliation: Departamento de Ciencias Básicas de la Salud, Área de Bioquímica y Genética Molecular. Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, Madrid, Spain.
authors.forename: Yurena
authors.initials: Y
authors.lastname: Vivas
authors.affiliation: Departamento de Ciencias Básicas de la Salud, Área de Bioquímica y Genética Molecular. Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, Madrid, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Velasco
authors.affiliation: Division of Nephrology/Hypertension, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Tet-Kin
authors.initials: TK
authors.lastname: Yeo
authors.affiliation: Division of Nephrology/Hypertension, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Chen
authors.affiliation: Departamento de Ciencias Básicas de la Salud, Área de Bioquímica y Genética Molecular. Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Medina-Gomez
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D007668:Kidney / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015638:Cytochalasin D; D019308:Palmitic Acid