| Abstract
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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.
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