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1 State University of New York at Buffalo
2 University at Buffalo, SUNY
3 Kaleida Health
* To whom correspondence should be addressed. E-mail: mspatel{at}buffalo.edu.
Our earlier studies have shown that artificial rearing of new born rat pups (first generation;1-HC) on a high carbohydrate (HC) milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Offspring (second generation; 2-HC) of 1-HC female rats spontaneously acquired the HC phenotype in the post-weaning period. In this study we have characterized the development of the abnormal intrauterine environment in the 1-HC female rats and the effects on fetal development under such pregnancy conditions for the offspring. 1-HC female rats demonstrated hyperphagia on lab chow and increased body weight gain beginning from the immediate post-weaning period along with hyperinsulinemia and hyperleptinemia. During pregnancy, 1-HC female rats showed several metabolic alterations including increased body weight gain, increased plasma levels of insulin, leptin, proinflammatory markers and lipid peroxidation products. Although there were no significant changes in the body weights or litter size of term 2-HC fetuses, the plasma levels of insulin and leptin were significantly higher compared with control term fetuses. Quantitation of mRNA levels by real-time RT-PCR indicated significant increases in the mRNA levels of orexigenic neuropeptides in the hypothalamus of 2-HC term fetuses. Collectively, these results indicate that the HC diet in infancy results in an adverse pregnancy condition in female rats with deleterious consequences for the offspring.
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