Apolipoprotein B mRNA editing and apolipoprotein gene expression in the liver of hyperinsulinemic fatty Zucker rats: Relationship to very low density lipoprotein composition

Marshall Elam, Matthew A. Von Wronski, Lauren Cagen, Fayanne Thorngate, Poonam Kumar, Murray Heimberg, Henry G. Wilcox

Research output: Contribution to journalArticle

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Abstract

We previously demonstrated increased apolipoprotein B (apoB) mRNA editing, elevated levels of mRNA for the catalytic component of the apoB mRNA editing complex, apobec-1, and increased secretion of the product of the edited mRNA, apoB48, in very low density lipoproteins (VLDL) in primary cultures of Sprague-Dawley rat hepatocytes following insulin treatment. In order to determine the effect of in vivo hyperinsulinemia on these processes, we determined apoB mRNA editing, apobec-1 expression, hepatic expression of mRNA for apoB and other VLDL apoproteins, and the quantity and composition of plasma VLDL in the hyperinsulinemic fatty Zucker rat. Total apoB mRNA content of the livers of the fatty rats and lean littermates did not differ; however, edited apoB message coding for hepatic apo B48, and abundance of mRNA for the catalytic subunit of the apoB mRNA editing complex, apobec-1, was increased by 1.7- and 3.3-fold, respectively, in fatty rats. ApoCIII mRNA abundance was increased in livers of fatty rats as well, but the abundance of hepatic apoE mRNA in the fatty animal was not different from that of the lean rat. Hepatic apoAI mRNA abundance was also increased in the fatty rats. Associated with increased apoB mRNA editing, was the 1.7-fold increase in the fraction of apoB in plasma as apoB48 in fatty rats. VLDL-triglyceride and -apoB in plasma were 15- and 3-fold higher, respectively, in fatty Zucker rats compared to lean littermates, indicating both enrichment of VLDL with triglycerides and increased accumulation of VLDL particles. Increased hepatic expression of mRNA for apoCIII and apoAI was associated with increased content of apoC (and relative depletion of apoE) in VLDL of fatty rats, and plasma apoAI was increased in fatty Zucker rats, primarily in the HDL fraction. The current study provides further evidence that chronic exposure to high levels of insulin influences both the quantity of and lipid/apoprotein composition of VLDL in plasma. The increased apoC and decreased apoE (as well as increased triglyceride) content of VLDL in the fatty Zucker rat observed in the current study may affect VLDL clearance and therefore may be a factor in the observed accumulation of VLDL in the plasma of the fatty hyperinsulinemic Zucker rats.

Original languageEnglish (US)
Pages (from-to)809-816
Number of pages8
JournalLipids
Volume34
Issue number8
DOIs
StatePublished - Sep 28 1999

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Zucker Rats
VLDL Lipoproteins
Apolipoproteins
Apolipoproteins B
Fatty Liver
Gene expression
Liver
Rats
Gene Expression
Messenger RNA
Chemical analysis
Plasmas
Apolipoproteins E
Apolipoprotein B-48
Apolipoproteins C
Apoproteins
Insulin
Hyperinsulinism

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

Cite this

Apolipoprotein B mRNA editing and apolipoprotein gene expression in the liver of hyperinsulinemic fatty Zucker rats : Relationship to very low density lipoprotein composition. / Elam, Marshall; Von Wronski, Matthew A.; Cagen, Lauren; Thorngate, Fayanne; Kumar, Poonam; Heimberg, Murray; Wilcox, Henry G.

In: Lipids, Vol. 34, No. 8, 28.09.1999, p. 809-816.

Research output: Contribution to journalArticle

Elam, Marshall ; Von Wronski, Matthew A. ; Cagen, Lauren ; Thorngate, Fayanne ; Kumar, Poonam ; Heimberg, Murray ; Wilcox, Henry G. / Apolipoprotein B mRNA editing and apolipoprotein gene expression in the liver of hyperinsulinemic fatty Zucker rats : Relationship to very low density lipoprotein composition. In: Lipids. 1999 ; Vol. 34, No. 8. pp. 809-816.
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AU - Heimberg, Murray

AU - Wilcox, Henry G.

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N2 - We previously demonstrated increased apolipoprotein B (apoB) mRNA editing, elevated levels of mRNA for the catalytic component of the apoB mRNA editing complex, apobec-1, and increased secretion of the product of the edited mRNA, apoB48, in very low density lipoproteins (VLDL) in primary cultures of Sprague-Dawley rat hepatocytes following insulin treatment. In order to determine the effect of in vivo hyperinsulinemia on these processes, we determined apoB mRNA editing, apobec-1 expression, hepatic expression of mRNA for apoB and other VLDL apoproteins, and the quantity and composition of plasma VLDL in the hyperinsulinemic fatty Zucker rat. Total apoB mRNA content of the livers of the fatty rats and lean littermates did not differ; however, edited apoB message coding for hepatic apo B48, and abundance of mRNA for the catalytic subunit of the apoB mRNA editing complex, apobec-1, was increased by 1.7- and 3.3-fold, respectively, in fatty rats. ApoCIII mRNA abundance was increased in livers of fatty rats as well, but the abundance of hepatic apoE mRNA in the fatty animal was not different from that of the lean rat. Hepatic apoAI mRNA abundance was also increased in the fatty rats. Associated with increased apoB mRNA editing, was the 1.7-fold increase in the fraction of apoB in plasma as apoB48 in fatty rats. VLDL-triglyceride and -apoB in plasma were 15- and 3-fold higher, respectively, in fatty Zucker rats compared to lean littermates, indicating both enrichment of VLDL with triglycerides and increased accumulation of VLDL particles. Increased hepatic expression of mRNA for apoCIII and apoAI was associated with increased content of apoC (and relative depletion of apoE) in VLDL of fatty rats, and plasma apoAI was increased in fatty Zucker rats, primarily in the HDL fraction. The current study provides further evidence that chronic exposure to high levels of insulin influences both the quantity of and lipid/apoprotein composition of VLDL in plasma. The increased apoC and decreased apoE (as well as increased triglyceride) content of VLDL in the fatty Zucker rat observed in the current study may affect VLDL clearance and therefore may be a factor in the observed accumulation of VLDL in the plasma of the fatty hyperinsulinemic Zucker rats.

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