High Fat High Cholesterol Diet Western Diet Aggravates Atherosclerosis, Hyperglycemia and Renal Failure in Nephrectomized LDL Receptor Knockout Mice: Role of Intestine Derived LipopolysaccharideReportar como inadecuado




High Fat High Cholesterol Diet Western Diet Aggravates Atherosclerosis, Hyperglycemia and Renal Failure in Nephrectomized LDL Receptor Knockout Mice: Role of Intestine Derived Lipopolysaccharide - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

A high fat meal, frequently known as western diet WD, exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide LPS leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2-3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet Nx or WD Nx+WD. The controls were sham operated animals on normal diet control and WD WD. To verify if LPS plays a role in exaggerating renal insufficiency, polymyxin PM, a known LPS antagonist, and curcumin CU, a compound known to ameliorate chronic kidney disease CKD, was given to Nx animals on western diet Nx+WD+PM and Nx+WD+CU, respectively. Compared to control, all other groups displayed increased circulatory LPS. The Nx+WD cohort had the highest levels of LPS. Nx group had significant renal insufficiency and glucose intolerance but not atherosclerosis. WD had intense atherosclerosis and glucose intolerance but it did not show signs of renal insufficiency. Compared to other groups, Nx+WD had significantly higher cytokine expression, macrophage infiltration in the kidney, renal insufficiency, glucose intolerance and atherosclerosis. PM treatment blunted the expression of cytokines, deterioration of renal function and associated disorders, albeit not to the levels of Nx, and was significantly inferior to CU. PM is a non-absorbable antibiotic with LPS binding properties, hence its beneficial effect can only be due to its effect within the GI tract. We conclude that LPS may not cause renal insufficiency but can exaggerate kidney failure and associated disorders following renal insufficiency.



Autor: Siddhartha S. Ghosh , Samuel Righi, Richard Krieg, Le Kang, Daniel Carl, Jing Wang, H. Davis Massey, Domenic A. Sica, Todd W. B.

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados