Abstract

A carbohydrate-rich diet induces glucose-6-phosphate dehydrogenase (G6PD) in liver parenchymal cells, which supports fatty acid synthesis de novo. Bacterial endotoxins stimulate G6PD expression in hepatic sinusoidal endothelial and Kupffer cells but not in parenchymal cells. This study was designed to elucidate whether G6PD expression is regulated uniformly by dietary carbohydrates in hepatic sinusoidal and parenchymal cells. Freshly isolated cells from five groups of Sprague-Dawley rats were analyzed for G6PD activity and mRNA abundance. The rats were grouped as follows: 1) food deprived for 24 h; 2) food deprived for 24 h followed by consumption of the standard diet for 48 h; 3) food deprived for 24 h followed by consumption of a carbohydrate-rich diet for 48 h; 4) fed standard diet; and 5) fed standard diet followed by consumption of a carbohydrate-rich diet for 48 h. In endothelial cells, G6PD activity was 150% greater in group 3 than in group 1 and 125% greater in group 5 than in group 4. Steady-state G6PD mRNA levels were elevated by 300% in endothelial cells from group 3 compared with those from group 1. In Kupffer cells, G6PD activity and mRNA abundance were not different among the groups. As expected, G6PD expression was 700–1200% greater in parenchymal cells from rats fed a carbohydrate diet (groups 3 and 5) than from controls. Our results indicate that short-term consumption of a carbohydrate-rich diet stimulates G6PD expression in endothelial and parenchymal cells. Because G6PD supports reactive oxygen metabolism, the response may represent a preconditioning of antioxidant pathways in the hepatic cell populations that are targets of sinusoid-born reactive oxygen species during infections.

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