TY - JOUR
T1 - Overexpression of apolipoprotein A5 in mice is not protective against body weight gain and aberrant glucose homeostasis
AU - Pamir, Nathalie
AU - McMillen, Timothy S.
AU - Li, Yu I.
AU - Lai, Ching Mei
AU - Wong, Howard
AU - LeBoeuf, Renée C.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (RO1 DK063159 [RCL]) and a VA Merit Review Grant (HW).
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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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U2 - 10.1016/j.metabol.2008.11.018
DO - 10.1016/j.metabol.2008.11.018
M3 - Article
C2 - 19303979
AN - SCOPUS:62349138735
SN - 0026-0495
VL - 58
SP - 560
EP - 567
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 4
ER -