Reduction of plasma triglycerides in apolipoprotein C-II transgenic mice overexpressing lipoprotein lipase in muscle.

Abstract

LPL and its specific physiological activator, apolipoprotein C-II (apoC-II), regulate the hydrolysis of triglycerides (TGs) from circulating TG-rich lipoproteins. Previously, we developed a skeletal muscle-specific LPL transgenic mouse that had lower plasma TG levels. ApoC-II transgenic mice develop hypertriglyceridemia attributed to delayed clearance. To investigate whether overexpression of LPL could correct this apoC-II-induced hypertriglyceridemia, mice with overexpression of human apoC-II (CII) were cross-bred with mice with two levels of muscle-specific human LPL overexpression (LPL-L or LPL-H). Plasma TG levels were 319 +/- 39 mg/dl in CII mice and 39 +/- 5 mg/dl in wild-type mice. Compared with CII mice, apoC-II transgenic mice with the higher level of LPL overexpression (CIILPL-H) had a 50% reduction in plasma TG levels (P = 0.013). Heart LPL activity was reduced by approximately 30% in mice with the human apoC-II transgene, which accompanied a more modest 10% decrease in total LPL protein. Overexpression of human LPL in skeletal muscle resulted in dose-dependent reduction of plasma TGs in apoC-II transgenic mice. Along with plasma apoC-II concentrations, heart and skeletal muscle LPL activities were predictors of plasma TGs. These data suggest that mice with the human apoC-II transgene may have alterations in the expression/activity of endogenous LPL in the heart. Furthermore, the decrease of LPL activity in the heart, along with the inhibitory effects of excess apoC-II, may contribute to the hypertriglyceridemia observed in apoC-II transgenic mice.

• Authors: Leslie K Pulawa, Dalan R Jensen, Alison Coates, Robert H Eckel
• Journal: Journal of lipid research (J Lipid Res) Vol. 48 Issue 1 Pg. 145-51 (Jan 2007) ISSN: 0022-2275 [Print] United States
• PMID: 17018885 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Triglycerides
• Lipoprotein Lipase

Topics

• Animals
• Humans
• Hypertriglyceridemia (enzymology, genetics)
• Lipoprotein Lipase (genetics)
• Mice
• Mice, Transgenic
• Muscle, Skeletal (enzymology)
• Myocardium (enzymology)
• Triglycerides (blood)