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Papers In Press, published online ahead of print February 16, 2005
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Department of Physiology, University of the Basque Country Medical School, Leioa, Vizcaya 48940
Corresponding Author: ofpocolb{at}lg.ehu.es
Zonation affects liver parenchymal cell function and metabolism as well as nonparenchymal cell activation, but whether VLDL production is zonated has yet to be elucidated. Infection induces enhanced VLDL secretion by the liver. Ex vivo studies were undertaken to examine the liver heterogeneity for VLDL formation and secretion and their in vivo response to endotoxin. Highly pure periportal and perivenous hepatocytes were isolated from fasted lipopolysaccharide-treated, fasted, and fed rats. They were used to asses their capacity to release VLDL apoB and lipid classes in relation to de novo lipid synthesis and the expression of crucial genes to VLDL production. Despite the common superior ability of periportal hepatocytes for lipid release and zonal differences in lipid synthesis, zonated secretion of VLDL particles was observed in septic but not in normal fed or fasted livers. The endotoxin-induced apoB secretion was more accentuated in periportal hepatocytes; this was accompanied by a preferential periportal rise in apoB and microsomal triglyceride transfer protein mRNA levels, whereas lipogenesis indicators were, if anything, similarly modified in hepatocytes of either acinar origin. We conclude that periportal and perivenous hepatocytes exhibited similar capabilities for VLDL formation/secretion in normal conditions; however, the endotoxic pressure did zonate periportally.
Revised on February 2, 2005
Accepted on February 6, 2005
Endotoxin promotes preferential periportal upregulation of VLDL secretion in the rat liver
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