Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

Journal Article · Fri Aug 15 04:00:00 EDT 2003 · Arteriosclerosis, Thrombosis & Vascular Biology

OSTI ID:834631

Baroukh, Nadine N ^[1]; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M; Fruchart, Jamila; Pennacchio, Len A

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1. LBNL Library

Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director. Office of Science. Office of Biological and Environmental Research. Life Science Division; National Institutes of Health. National Heart, Lung, and Blood Institute. Programs for Genomic Application Grants HL66681 and HL071954A (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 834631
• Report Number(s): LBNL--53764
• Journal Information: Arteriosclerosis, Thrombosis & Vascular Biology, Journal Name: Arteriosclerosis, Thrombosis & Vascular Biology Journal Issue: 7 Vol. 24
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
APOLIPOPROTEINS
GENES
HUMAN CHROMOSOMES
MICE
PLASMA
PROTEINS
TRIGLYCERIDES