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Escherichia coli sepsis increases hepatic apolipoprotein B secretion by inhibiting degradation

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Lipids

Abstract

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 3.8×108 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 coli sepsis increased celular 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. coli 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.

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Abbreviations

apo:

apolipoprotein

BSA:

bovine serum albumin

ELISA:

enzyme-linked immunosorbent assay

LDL:

low density lipoprotein

LPL:

lipoprotein lipase

RT-PCR:

reverse transcription-polymerase chain reaction

TG:

triglyceride

TNF:

tumor necrosis factor

TNF-α:

tumor necrosis factor alpha

VLDL:

very low density lipoprotein

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Authors and Affiliations

  1. Department of Medicine, University of Chicago, 60637, Chicago, Illinois

    Ken-Ichi Hirano & Nicholas O. Davidson

  2. Department of Surgery, Jefferson Medical College, Room 603 College Bldg. 1025 Walnut St., 19107, Philadelphia, PA

    Hope W. Phetteplace, Natalia Sedkova & Susan P. Lanza-Jacoby

Authors
  1. Hope W. Phetteplace
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  2. Natalia Sedkova
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  3. Ken-Ichi Hirano
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  4. Nicholas O. Davidson
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  5. Susan P. Lanza-Jacoby
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Corresponding author

Correspondence to Susan P. Lanza-Jacoby.

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Phetteplace, H.W., Sedkova, N., Hirano, KI. et al. Escherichia coli sepsis increases hepatic apolipoprotein B secretion by inhibiting degradation. Lipids 35, 1079–1086 (2000). https://doi.org/10.1007/s11745-000-0622-y

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  • DOI: https://doi.org/10.1007/s11745-000-0622-y

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