Endotoxin-mediated hepatic lipid accumulation during parenteral nutrition in rats

Objective: To assess the effect of endotoxernia on hepatic lipid content during parenteral nutrition (PN) in rats. Methods: Twenty male Sprague-Dawley rats (185-230 gm) were randomized to receive PN (n=9) or PN plus a continuous infusion of E. coli 026:136 lipopolysaccharide (LPS; n= 11). All animals received isocaloric (170 kcal/kg/day), isonitrogenous (1.1 g N/kg/day), glucose-based PN for the next 78 hours. After 30 hours of adaptation to TPN, the animals were randomized to receive PN or PN plus LPS at 6 mg/kg/day for the remaining 48 hours of study. The animals were euthanized and the livers were harvested. Results: Liver weight increased significantly (by 60%) from 7.5 +/- 0.6 g to 12.1 +/- 2.4 g (P less than or equal to 0.01) in the animals who received PN versus LPS, respectively. The proportion of liver water remained the same for PN and LPS groups (72.9 +/- 3.2% versus 72.3 +/- 3.8%, respectively, p = N.S.). However, liver fat increased disproportionately (by about 130%) from 0.20 +/- 0.05 g to 0.46 +/- 0.20 g (p less than or equal to 0.01) total fat weight or from 9.6 +/- 1.8% to 13.6 +/- 4.1% (p less than or equal to 0.02) lipid content (g/g) of the dry liver weight for the PN and LPS groups, respectively. Conclusion: Endotoxin, when given concomitantly with parenteral nutrition, increases hepatic lipid accumulation and thus augments the development of parenteral nutrition-associated fatty liver in rats.