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Am J Physiol Regul Integr Comp Physiol (February 4, 2009). doi:10.1152/ajpregu.90932.2008
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Submitted on November 18, 2008
Revised on January 22, 2009
Accepted on January 28, 2009

Developmental programming of lipid metabolism and Aortic Vascular Function in C57Bl/6 Mice: A novel study suggesting an involvement of LDL-receptor

Kanta Chechi1, John J McGuire1, and Sukhinder Kaur Cheema1*

1 Memorial University

* To whom correspondence should be addressed. E-mail: skaur{at}mun.ca.

We have previously shown that a maternal high-fat diet, rich in saturated fatty acids (SFA), alters the lipid metabolism of their adult offspring. The current study was designed to investigate 1) whether alterations in hepatic LDL-receptor (LDL-r) expression may serve as a potential mechanism of developmental programming behind the altered lipid metabolism of the offspring 2) whether altered lipid metabolism leads to aortic vascular dysfunction in the offspring 3) whether deleterious effects of SFA exposure pre-weaning are influenced by post-weaning diet and 4) whether gender specific programming effects are observed. Female C57Bl/6 mice were fed a high SFA diet or regular chow during gestation and lactation while their pups, both male and female, received either SFA or a chow diet after weaning. Male offspring obtained from mothers fed SFA diet and those who continued on chow post-weaning had higher plasma triglycerides and total-cholesterol, whereas female offspring had higher plasma total- and LDL-cholesterol levels, lower hepatic LDL-r mRNA expression and reduced aortic contractile responses compared to the offspring that were fed chow throughout. A comparison of the post-weaning diet revealed significantly lower hepatic LDL-r expression alongwith significantly higher plasma LDL-cholesterol concentration in the female offspring that were obtained from mothers fed SFA diet and who continued on SFA diet post-weaning as compared to the female offspring that were obtained from mothers fed SFA diet but who continued on chow post-weaning. In conclusion, we report a novel observation of hepatic LDL-r mediated programming of altered lipid metabolism, alongwith aortic vascular dysfunction, in the female offspring of mothers fed a high SFA diet. Male offspring only exhibited dyslipidemia suggesting gender mediated "programming". This study further highlighted the role of post-weaning diets in overriding the effects of maternal programming.







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