Endotoxin-Mediated Hepatic Lipid Accumulation During Parenteral Nutrition in Rats

Abstract

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 ≤ 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 ≤ 0.01) total fat weight or from 9.6 ± 1.8% to 13.6 ± 4.1% (p ≤ 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.

• parenteral nutrition
• endotoxin
• lipopolysaccharide
• cholestasis
• liver disease
• rat

The assistance of Jean-Jacques Rajter, B.A. and R. Gregg Settle, Ph.D. is acknowledged. This study was supported in part by a Veterans Affairs Merit Review Grant (R.G.S.) and by an Academic Research Enhancement Award (R.N.D.) from the Public Health Service (1R15DK46545-01). The amino acids (FreAmine III™), trace minerals and intravenous nutrient bags were kindly donated by B Braun, Inc. (Irvine, CA).