Human epidemiological studies have shown that low birth weight is associated with glucose intolerance, insulin resistance, obesity and type 2 diabetes in the adult. In rats, experimental induction of intrauterine growth retardation leads to abnormal glucose metabolism in the adult offspring but whether these abnormalities track from fetal life remains unclear (1). Short-term undernutrition of sheep during late gestation has been shown to alter fetal hepatic gluconeogenic enzyme activities (2). However, little is known about the effects of prolonged dietary manipulation during pregnancy on hepatic glucogenic capacity. Therefore, this study measured hepatic glycogen content and activity of glucose-6-phosphatase (G6Pase), the final enzyme in the glucogenic pathways, in pregnant rats and their fetuses after maternal protein deprivation throughout pregnancy. Pregnant Wistar rats were fed either an 8% protein diet (LP, n=7), or a standard 20% protein diet (CON, n=4) throughout pregnancy. After terminal anaesthesia on day 20 of a 21 day gestation, maternal and fetal livers were collected and frozen for later analysis of G6Pase activity (3) and glycogen content (4). Blood glucose concentration was measured with a glucometer after decapitation of each pup. Sex of the pups was determined by measuring ano-genital distance. Livers from two males and two females from each litter were analysed. Data were analysed via Students t test. Litter means (± SEM) are reported below. Fetal body weight was significantly less in LP than CON (LP 3.4 ± 0.1g vs. CON 3.8 ± 0.1g; p<0.001) but was not affected by their sex. Fetal plasma glucose did not differ with diet (LP 4.6 ± 0.3mM (n=7) vs. CON 4.5 ± 0.2mM (n=4)) or between sexes (LP male 4.3 ± 0.4 (n=7) vs. LP female 4.7 ± 0.3 (n=7); CON male 4.2 ± 0.1 (n=4) vs. CON female 4.7 ± 0.2 (n=4)). Maternal G6Pase activity and glycogen content, and fetal glycogen content were significantly higher with the LP than CON diet, while fetal hepatic G6Pase did not differ with diet (Table 1). There were no significant differences in fetal hepatic G6Pase activity or glycogen content with pup sex with each diet. These findings indicate that prolonged protein deprivation during rat pregnancy enhances both the maternal and fetal glucogenic capacity by late gestation. The changes in glucose metabolism observed in adult rats protein-deprived in utero may, therefore, be present much earlier in life.
University College London 2006 (2006) Proc Physiol Soc 3, C115
Oral Communications: Differential effects of a low protein diet throughout pregnancy on glucose-6-phosphatase and glycogen content in maternal and fetal rat liver
Kathryn L Franko1, Alison J Forhead1, Abigail L Fowden1
1. Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
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Table 1: Hepatic G6Pase activity and glycogen content in mothers and fetuses on different diets
Where applicable, experiments conform with Society ethical requirements.