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Endotoxin-mediated hepatic lipid accumulation during parenteral nutrition in rats
Roland N Dickerson1, Claudia B Karwoski
1Department of Pharmacy, The University of Tennessee Health Sciences Center, Memphis 38163, USA.
Objective:
To assess the effect of endotoxemia 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:B6 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 < or = 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 < or = 0.01) total fat weight or from 9.6+/-1.8% to 13.6+/-4.1% (p < or = 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.