Persistence of metabolic consequences in the progeny of rats fed a HC formula in their early postnatal life

Abstract

First-generation (1-) male and female rat pups were either reared artificially on a high-carbohydrate (HC) or a high-fat (HF) formula or nursed by mother (MF) from day 4 and weaned onto a stock diet on day 24. 1-HC rats compared with sex-matched control rats (1-HF and 1-MF) were hyperinsulinemic and mildly obese by day 60. We investigated the effect of maternal hyperinsulinemia on the second generation (2-) by intragroup breeding. The 2-HC male and female rats were hyperinsulinemic on day 45, had significantly increased growth rate from approximately day 60 onward, and became obese as evidenced by increased adipose tissue mass due to hypertrophy on day 100. The lipogenic capacity of liver and adipose tissues was significantly higher in the 2-HC than in control rats. Thus the metabolic changes that occurred in the first-generation rats fed a HC formula during early postnatal life not only persisted into their adult life but were also passed on to the next generation.

Metabolic Programming: Causes and Consequences

“…2 The growth pattern of HC rats in the second generation parallels that of first generation HC rats (35) (Fig. 1B).…”

“…1B). Female rats fed an HC milk formula during their suckling period spontaneously transmitted their metabolic characteristics to their progeny without the pups themselves having to undergo any nutritional treatment (35). The second generation HC rats display hyperinsulinemia and an altered insulin secretory pattern within 48 h after weaning them onto laboratory chow on day 24.…”

The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk

“…Overfeeding in the neonatal period has been shown to produce second generation effects on glucose homeostasis (Laychock et al 1995, Vadlamudi et al 1995, Patel et al 2001, Srinivasan et al 2003.…”

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype

“…Earlier, we showed that the overlap of an altered nutritional experience in the form of a high-carbohydrate (HC) milk formula with the critical window of postnatal organ development in neonatal rat pups resulted in the establishment of the HC phenotype (chronic hyperinsulinemia and adult-onset obesity) in these rats (19,26). Because of fetal development in HC female rats, adult progeny demonstrated the same HC phenotype (29). Whether the adaptations that predispose the progeny for expression of the HC phenotype in adult life occur during fetal development in the HC intrauterine environment was not explored in the earlier study.…”

“…The mere switch in the major source of calories from fat in rat milk to carbohydrate in the HC milk formula without alterations in total caloric intake results in the immediate onset of hyperinsulinemia, its persistence even after its withdrawal on postnatal day 24, and adult-onset obesity occurring in both male and female rats (9,10,28). A significant observation from these studies was that firstgeneration female rats (1-HC) that were artificially reared on the HC milk formula in their immediate postnatal period spontaneously transmitted the HC phenotype of chronic hyperinsulinemia and adult-onset obesity to their progeny (2nd generation HC; 2-HC) without the necessity for any dietary intervention in 2-HC rats (29). Cross-breeding experiments showed that only 1-HC female rats and not 1-HC male rats could effect this transfer to the progeny, indicating that it is the fetal development in the intrauterine environment of the 1-HC female rat that predisposes them for metabolic malprogramming (S. Vadlamudi, M. Srinivasan, and M. S. Patel, unpublished observations).…”