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Role of oxidized low density lipoproteins and free fatty acids in the pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes

Nosadini, Romano and Tonolo, Giancarlo (2011) Role of oxidized low density lipoproteins and free fatty acids in the pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes. Nutrition, Metabolism and Cardiovascular Diseases, Vol. 21 (2), p. 79-85. eISSN 1590-3729. Article.

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DOI: 10.1016/j.numecd.2010.10.002

Abstract

Oxidized lipids initiate and modulate the inflammatory cellular events in the arterial wall and the formation of macrophage foam cells. CD36 mediates the cellular uptake of ox-LDL through its recognition of specific truncated fatty acid moieties and oxidized phosphatidylcholine. Evidence has been reported that chemokine CXCL16, rather than CD36, is the main scavenger receptor in human podocytes mediating the uptake of ox-LDL. Ox-LDL induces loss of nephrin expression from cultured podocytes. It has been recently shown that nephrin once phosphorilated associates with PI3K and stimulates the Akt dependent signaling. This pathway plays a critical role in nephrin-actin-dependent cytoskeleton activation and remodeling, in the control of protein trafficking and in podocyte survival. An enhanced FFA uptake by podocytes is mediated by increased C36 scavenger receptor expression, together with a decrease of betaoxidation and in turn intracellular lipid accumulation. Accumulated FFA that is trapped into the mitochondrial matrix leads to mitochondrial ROS production, lipid peroxidation and mitochondrial damage and dysfunction. A disturbed transport and oxidation of FFA, paralleled by an impaired antioxidant response, damages podocyte structure and leads to glomerulopathy in early stages of nephrosis. Increased triglyceride synthesis and ox-and glycated LDL uptake by mesangial cells may also contribute to determine diabetic glomerulopathy. Oxidative processes are pivotal events in injury to renal tubular and epithelial cells exposed to ox-LDL. Notably CXCL16 are the main receptors for the uptake of ox-LDL in podocytes, whereas CD36 plays this role in tubular renal cells. In overt type 2 diabetes Ox-LDL and FFA damage podocyte function, SD-podocyte structure and tubulointerstitial tissue, at least partially, through different pathogenetic mechanisms.
Further studies are needed to investigate the role of Ox-LDL and FFA on renal complications in obese, insulin resistant patients before the development of diabetes. The aim of the present review is to briefly elucidate the patterns of systemic lipid metabolism and the individual effects of lipotoxicity at glomerular and tubular level in the kidney of overt type 2 diabetic patients. These findings better elucidate our knowledge of diabetic glomerulopathy, beside and along with previous findings, in vivo and in vitro, on ox-LDL and FFA effects in mesangial cells.

Item Type:Article
ID Code:5436
Status:Published
Refereed:Yes
Uncontrolled Keywords:Glomerular filtration rate, albumin excretion rate, oxidized low density lipoproteins, CD36, scavenger receptors
Subjects:Area 06 - Scienze mediche > MED/13 Endocrinologia
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL2, Olbia > Servizio aziendale di diabetologia e malattie metaboliche
Publisher:Elsevier
eISSN:1590-3729
Copyright Holders:© 2010 Elsevier
Deposited On:08 Feb 2011 11:13

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