Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL.

Abstract

Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipid levels independently of effects of apoE on lipid metabolism by comparing apolipoprotein E gene-deficient/apolipoprotein C-I gene-deficient (apoe-/-apoc1-/-), apoe-/-apoc1+/-, and apoe-/-apoc1+/+ mice. The presence of the apoC-I gene-dose-dependently increased plasma cholesterol (+45%; P < 0.001) and triglycerides (TGs) (+137%; P < 0.001), both specific for VLDL. Whereas apoC-I did not affect intestinal [3H]TG absorption, it increased the production rate of hepatic VLDL-TG (+35%; P < 0.05) and VLDL-[35S]apoB (+39%; P < 0.01). In addition, apoC-I increased the postprandial TG response to an intragastric olive oil load (+120%; P < 0.05) and decreased the uptake of [3H]TG-derived FFAs from intravenously administered VLDL-like emulsion particles by gonadal and perirenal white adipose tissue (WAT) (-34% and -25%, respectively; P < 0.05). As LPL is the main enzyme involved in the clearance of TG-derived FFAs by WAT, and total postheparin plasma LPL levels were unaffected, these data demonstrate that endogenous apoC-I suffices to attenuate the lipolytic activity of LPL. Thus, we conclude that endogenous plasma apoC-I increases VLDL-total cholesterol and VLDL-TG dose-dependently in apoe-/- mice, resulting from increased VLDL particle production and LPL inhibition.

• Authors: Marit Westerterp, Willeke de Haan, Jimmy F P Berbée, Louis M Havekes, Patrick C N Rensen
• Journal: Journal of lipid research (J Lipid Res) Vol. 47 Issue 6 Pg. 1203-11 (Jun 2006) ISSN: 0022-2275 [Print] United States
• PMID: 16537968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein C-I
• Apolipoproteins C
• Apolipoproteins E
• Lipoproteins, VLDL
• Cholesterol
• Lipase
• Lipoprotein Lipase

Topics

• Animals
• Apolipoprotein C-I
• Apolipoproteins C (blood, genetics, physiology)
• Apolipoproteins E (blood, genetics, physiology)
• Cholesterol (blood, metabolism)
• Hyperlipidemias (blood, metabolism)
• Intestinal Mucosa (metabolism)
• Lipase (metabolism)
• Lipoprotein Lipase (analysis, blood, metabolism)
• Lipoproteins, VLDL (analysis, biosynthesis, blood)
• Liver (metabolism)
• Mice
• Mice, Knockout
• Postprandial Period