Escherichia coli sepsis increases hepatic apolipoprotein B secretion by inhibiting degradation

Sepsis leads to hypertriglyceridemia in both humans and animals. Previously , we reported that plasma very low density lipoprotein apolipoprotein (apo) B and hepatic production of apoB increased during Escherichia coil sepsis. The present experiments were undertaken to determine whether the altered h epatic secretion of apoB was associated with an increase in synthesis or a decrease in degradation rate. Sepsis was induced in male, Lewis rats (225-2 75 g) by intravenous injection of 3.8 x 10(8) live E, coli colonies/100 g b ody. Twenty-four hours later rats were sacrificed, and primary hepatocytes were prepared and incubated overnight with S-35-methionine. Hepatocytes fro m E. coli-treated rats secreted twice as much apoB-48 and total apoB than t he hepatocytes from control rats. Escherichia coil sepsis increased cellula r triglyceride mass by 86%, which was due to a stimulation in triglyceride synthesis from newly synthesized fatty acids, measured by (H2O)-H-3 incorpo ration into triglycerides. The apoB synthesis rate, apoB mRNA levels, and a poB mRNA editing were not altered during E. coli sepsis. The pulse-chase ex periments showed that the rate of apoB degradation decreased in E. coli-tre ated rats. These findings demonstrate that the secretion of apoB is regulat ed posttranslationally during E. coil sepsis by decreasing the degradation of newly synthesized apoB, which contributes to the development of hypertri glyceridemia.