Effects of a Maternal Ketogenic Diet on Maternal and Offspring Metabolic Health in Mice

Abstract

Ketogenic (keto) diets have gained popularity due to their potential benefits on weight loss and metabolic conditions. However, the consequences of consuming a keto diet before, during, and after pregnancy on maternal and offspring health remain incompletely understood. To investigate this, female Swiss Webster mice were randomly assigned to either a keto or control diet. After 6 weeks on diet, females were mated and maintained on their respective diets throughout pregnancy and lactation. In experiment 1, glucose tolerance tests (GTT) were performed on pregnant dams at gestational day (GD) 16.5. At GD 17.5, dams were euthanized, urine was collected for ketone analysis, and fetal and placental weights were recorded. In experiment 2, dams delivered naturally and one male and one female offspring per dam were retained and weighed weekly. At 12 weeks of age, offspring underwent GTT, followed by euthanasia and serum collection for insulin and leptin analysis. Compared with controls, keto dams exhibited increased body weight, impaired glucose tolerance, elevated urinary ketones, and reduced circulating insulin during late gestation (p<0.05). Fetuses from keto dams were significantly smaller (p<0.05), whereas placental weight and placental efficiency were unchanged. Offspring from keto dams weighed less than controls during early postnatal development but demonstrated catch-up growth by 12 weeks of age. At 12 weeks, keto offspring exhibited a modest but statistically significant improvement in glucose tolerance compared to control offspring (p<0.05). Male keto offspring had significantly decreased serum insulin (p<0.05) compared to male control offspring, while no differences were observed in females. Serum leptin levels did not differ between diet groups, although sex differences present in control offspring were not observed in keto offspring. Together, these findings suggest that maternal ketogenic diet consumption is associated with altered maternal glucose homeostasis during pregnancy and reduced fetal growth in this mouse model. Although offspring exhibited only modest metabolic alterations during early adulthood, the observed changes in growth trajectory and sex-specific metabolic profiles support further investigation into the long-term consequences of maternal ketogenic diet exposure during pregnancy.