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 coli sepsis. The present experiments were undertaken to determine whether the altered hepatic secretion of apoB was associated with an increase in synthesis or a decrease in degradation rate. Sepsis was induced in male, Lewis rats (225-275 g) by intravenous injection of 3.8 x 10(8) live E. coli colonies/100 g body. Twenty-four hours later rats were sacrificed, and primary hepatocytes were prepared and incubated overnight with 35S-methionine. Hepatocytes from E. coli-treated rats secreted twice as much apoB-48 and total apoB than the hepatocytes from control rats. Escherichia coil sepsis increased cellular triglyceride mass by 86%, which was due to a stimulation in triglyceride synthesis from newly synthesized fatty acids, measured by 3H2O incorporation into triglycerides. The apoB synthesis rate, apoB mRNA levels, and apoB mRNA editing were not altered during E. coil sepsis. The pulse-chase experiments showed that the rate of apoB degradation decreased in E. coli-treated rats. These findings demonstrate that the secretion of apoB is regulated posttranslationally during E. coli sepsis by decreasing the degradation of newly synthesized apoB, which contributes to the development of hypertriglyceridemia.
Phetteplace
H W
HW
Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Sedkova
N
N
Hirano
K I
KI
Davidson
N O
NO
Lanza-Jacoby
S P
SP
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis*; D015152:Blotting, Northern; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000382:microbiology; D008099:Liver / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018805:Sepsis / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol