Maternal Undernutrition Results in Transcript Changes in Male Offspring that May Promote Resistance to High Fat Diet Induced Weight Gain

Maternal nutrition during embryonic development and lactation influences multiple aspects of offspring health. Using mice, this study investigates the effects of maternal caloric restriction (CR) during mid-gestation and lactation on offspring neonatal development and on adult metabolic function when challenged by a high fat diet (HFD). The CR maternal model produced male and female offspring that were significantly smaller, in terms of weight and length, and females had delayed puberty. Adult offspring born to CR dams had a sexually dimorphic response to the high fat diet. Compared to offspring of maternal control dams, adult female, but not male, CR offspring gained more weight in response to high fat diet at 10 weeks. In adipose tissue of male HFD offspring, maternal undernutrition resulted in blunted expression of genes associated with weight gain and increased expression of genes that protect against weight gain. Regardless of maternal nutrition status, HFD male offspring showed increased expression of genes associated with nonalcoholic liver disease (NAFLD). Furthermore, we observed significant, sexually dimorphic differences in serum TSH. These data reveal tissue- and sex-specific changes in gene and hormone regulation following mild maternal undernutrition, which may offer protection against diet induced weight gain in adult male offspring. Male FVB.129P2 mice were singly housed for at least 24 hours prior to mating. Female FVB.129P2 mice were introduced to males in the evening of proestrus (embryonic day -1), which was determined by vaginal cytology. Vaginal plugs were visualized the next morning to confirm that mating occurred. Embryonic day 0 (E0) was established as the day after mating, when the vaginal plug was visualized. On E0, mated females were singly housed and weighed. At E10, females were again weighed to verify pregnancy with an expected 3 g increase in weight from E0. Pregnant females, or dams, received ~25 g of food daily starting at E12 to visually acclimate to receiving less food. Dams were paired into two feeding groups: ad libitum (FED) and 20% calorie restricted (CR20). At E15, the caloric restriction began, with CR20 dams receiving 80% of the food the paired FED dam consumed from the previous day. Food intake was measured daily around 0930. The undernutrition continued until the offspring were euthanized or weaned. There was one exception to this protocol: The day before parturition, the FED dams consumed less than 3 g of food. To prevent CR20 dams from consuming young at any point in the study, 3 g of food was the minimum made available to CR20 dams. Therefore, if the FED dams consumed less than 3 g of food before parturition, available food to undernourished dams was not reduced below 3 g. Pups were born around E19, with the average litter size being 8±1 pups.