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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Kiss, E; Kränzlin, B; Wagenblaβ, K; Bonrouhi, M; Thiery, J; Gröne, E; Nordström, V; Teupser, D; Gretz, N; Malle, E; Gröne, HJ.
Lipid droplet accumulation is associated with an increase in hyperglycemia-induced renal damage: prevention by liver X receptors.
Am J Pathol. 2013; 182(3):727-741 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Malle Ernst
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Abstract:
Dyslipidemia is a frequent component of the metabolic disorder of diabetic patients contributing to organ damage. Herein, in low-density lipoprotein receptor-deficient hyperlipidemic and streptozotozin-induced diabetic mice, hyperglycemia and hyperlipidemia acted reciprocally, accentuating renal injury and altering renal function. In hyperglycemic-hyperlipidemic kidneys, the accumulation of Tip47-positive lipid droplets in glomeruli, tubular epithelia, and macrophages was accompanied by the concomitant presence of the oxidative stress markers xanthine oxidoreductase and nitrotyrosine, findings that could also be evidenced in renal biopsy samples of diabetic patients. As liver X receptors (LXRα,β) regulate genes linked to lipid and carbohydrate homeostasis and inhibit inflammatory gene expression in macrophages, the effects of systemic and macrophage-specific LXR activation were analyzed on renal damage in hyperlipidemic-hyperglycemic mice. LXR stimulation by GW3965 up-regulated genes involved in cholesterol efflux and down-regulated proinflammatory/profibrotic cytokines, inhibiting the pathomorphology of diabetic nephropathy, renal lipid accumulation, and improving renal function. Xanthine oxidoreductase and nitrotyrosine levels were reduced. In macrophages, GW3965 or LXRα overexpression significantly suppressed glycated or acetylated low-density lipoprotein-induced cytokines and reactive oxygen species. Specifically, in mice, transgenic expression of LXRα in macrophages significantly ameliorated hyperlipidemic-hyperglycemic nephropathy. The results demonstrate the presence of lipid droplet-induced oxidative mechanisms and the pathophysiologic role of macrophages in diabetic kidneys and indicate the potent regulatory role of LXRs in preventing renal damage in diabetes.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Benzoates - pharmacology
Benzylamines - pharmacology
Cytokines - metabolism
Diabetes Mellitus, Experimental - complications
Diabetic Nephropathies - complications
Endothelial Cells - drug effects
Fibrosis -
Humans -
Hyperglycemia - complications
Hyperlipidemias - complications
Inflammation - pathology
Kidney - drug effects
Kidney Function Tests -
Lipid Metabolism - drug effects
Macrophages - drug effects
Mesangial Cells - drug effects
Mice -
Mice, Inbred C57BL -
Orphan Nuclear Receptors - metabolism
Oxidative Stress - drug effects
Podocytes - drug effects

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