Abstract
Apolipoprotein A5 (APOA5) is expressed primarily in the liver and modulates plasma
triglyceride levels in mice and humans. Mice overexpressing APOA5 exhibit reduced
plasma triglyceride levels. Because there is a tight association between plasma triglyceride
concentration and traits of the metabolic syndrome, we used transgenic mice overexpressing
human APOA5 to test the concept that these mice would be protected from diet-induced
obesity and insulin resistance. Male and female transgenic and wild-type mice on the
FVB/N genetic background were fed standard rodent chow or a diet rich in fat and sucrose
for 18 weeks, during which time clinical phenotypes associated with obesity and glucose
homeostasis were measured. We found that APOA5 transgenic (A5tg) mice were resistant
to diet-induced changes in plasma triglyceride but not total cholesterol levels. Body
weights were similar between the genotypes for females and males, although male A5tg
mice showed a modest but significant increase in the relative size of inguinal fat
pads. Although male A5tg mice showed a significantly increased ratio of plasma glucose
to insulin, profiles of glucose clearance as evaluated after injections of glucose
or insulin failed to reveal any differences between genotypes. Overall, our data showed
that there was no advantage to responses to diet-induced obesity with chronic reduction
of plasma triglyceride levels as mediated by overexpression of APOA5.
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Article info
Publication history
Accepted:
November 11,
2008
Received:
July 11,
2008
Identification
Copyright
© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
