Significant alterations in maternal nutrition may induce long-term metabolic consequences in offspring, in particular obesity and leptin and insulin resistance. Although maternal nutrient deprivation has been well characterized in this context, there is a relative paucity of data on how high fat (HF) nutrition impacts on the subsequent generation. The present study investigated the effects of maternal HF nutrition either throughout the mother's life up to and including pregnancy and lactation or HF nutrition restricted to pregnancy and lactation, on growth and metabolic parameters in male and female offspring. Virgin Wistar rats were assigned to one of three experimental groups: (1) controls (Cont): dams fed a standard chow diet throughout their life and throughout pregnancy and lactation; (2) maternal high fat (MHF) group: dams fed a HF diet from weaning up to and throughout pregnancy and lactation; and (3) pregnancy and lactation high fat (PLHF): dams fed a chow diet through their life until conception and then fed a HF diet throughout pregnancy and lactation. At weaning, all offspring were fed either a chow or HF diet for the remainder of the study (160 days). Litter size and sex ratios were not significantly different between the groups. MHF and PLHF offspring had significantly lower body weights and were hypoleptinaemic and hypoinsulinaemic at birth compared to Cont offspring. As adults however, chow-fed MHF and PLHF offspring were significantly more obese than Cont offspring (DEXA scanning at day 150, P < 0.001 for maternal HF diet). As expected a postweaning HF diet resulted in increased adiposity in all groups; MHF and PLHF offspring, however, always remained significantly more obese than Cont offspring. Increased adiposity in MHF and PLHF offspring was paralleled by hyperinsulinaemia and hyperleptinaemia (P < 0.001; MHF and PLHF versus Cont). It is of interest that a lifetime of HF nutrition produced a similar offspring phenotype to HF nutrition restricted to pregnancy and lactation alone, thus suggesting that the postnatal sequelae of maternal HF nutrition occurs independent of preconceptional diet. These data further reinforce the importance of maternal nutrition during these critical windows of development and show that maternal HF feeding can induce a markedly obese phenotype in male and female offspring completely independent of postnatal nutrition. Obesity and its sequelae may prove to be the greatest threat to human lifestyle and health in the developed world this century (Armitage et al. 2008). The obesity epidemic has seen the incidence of obesity and overweight almost double in Western societies and the trend is mirrored in developing nations that are transitioning to first-world economies. Obesity is strongly associated with the morbidities of type 2 diabetes, hypertension and ischaemic heart disease and represents an enormous burden to the health care system. Of even more concern is the rise of over 40% over the last 20 years in the prevalence of childhood obesity -with concomitant increases...

We have demonstrated for the first time that both birth weight and weight gain in childhood are associated with age at menarche. Weight gain before birth and subsequent weight gain up to the age of 8 yr were found to have opposing influences on the timing of menarche. Lower EBW combined with higher BMI during childhood predicted early age at menarche, and this relationship existed across normal birth weight and BMI ranges.

Our aim was to determine the postnatal effects of single and repeated glucocorticoid injections during late gestation. Repeated (104, 111, 118, 125 days) or single (104 days) injections of betamethasone or saline were given to the ewe or by ultrasound guided injection to the fetus (term 150 days). Lambs were born spontaneously and studied at 3 and 6 mo and 1 yr of age. Arterial pressure was measured at each age, and we performed intravenous glucose tolerance tests at 6 mo and 1 yr. Repeated maternal, but not single maternal or fetal, betamethasone injections prolonged gestation, reduced weight at birth and 3 mo, and was associated with low arterial pressure at 3 mo but not at 6 mo and 1 yr. Glucose metabolism was altered in all betamethasone treatment groups, regardless of the number or route of injections. Our data demonstrate that glucocorticoid-induced fetal growth restriction is associated with a transient reduction in postnatal arterial pressure, but glucocorticoid exposure with or without growth restriction alters glucose metabolism.

Shifts in the maternal gut microbiome have been implicated in metabolic adaptations to pregnancy. We investigated how pregnancy and diet interact to influence the composition of the maternal gut microbiota. Female C57BL/6 mice were fed either a control or a high fat diet for 8 weeks prior to mating. After confirmation of pregnancy, maternal weight gain and food intake were recorded. Fecal pellets were collected at 2 timepoints prior to mating (at the beginning of the experiment, and after 6 weeks of the specified diet) and at 4 timepoints during pregnancy (gestation day 0.5, 5.5, 10.5, and 15.5). The microbial composition and predicted metabolic functionality of the non-pregnant and pregnant gut was determined via sequencing of the variable 3 region of the 16S rRNA gene. Upon conception, differences in gut microbial communities were observed in both control and high fat-fed mice, including an increase in mucin-degrading bacteria. Control versus high fat-fed pregnant mice possessed the most profound changes to their maternal gut microbiota as indicated by statistically significant taxonomic differences. High fat-fed pregnant mice, when compared to control-fed animals, were found to be significantly enriched in microbes involved in metabolic pathways favoring fatty acid, ketone, vitamin, and bile synthesis. We show that pregnancy-induced changes in the female gut microbiota occur immediately at the onset of pregnancy, are vulnerable to modulation by diet, but are not dependent upon increases in maternal weight gain during pregnancy. High fat diet intake before and during pregnancy results in distinctive shifts in the pregnant gut microbiota in a gestational-age dependent manner and these shifts predict significant differences in the abundance of genes that favor lipid metabolism, glycolysis and gluconeogenic metabolic pathways over the course of pregnancy.