The offspring of obese mothers are at increased risk of metabolic disease during their lifetime, with maternal obesity at the time of conception a known risk. We aimed to determine if maternal weight loss in the preconception period improves metabolic outcomes in the offspring, and whether it is preferable to diet modulation in pregnancy.
Methods:
Female C57BL/6 mice were fed either high-fat diet (HFD) or chow diet (control) for 8 weeks. In HFD-fed dams, diet modification (switch to chow) or liraglutide treatment (0.3mg/kg s.c. for 4 weeks) was used to induce pre-conceptional weight los, resulting in 4 groups. A fifth group of HFD-fed dams had their diet modified to chow once pregnancy was confirmed. Following birth, male and female offspring were weaned to HFD or chow diet. At 12 weeks of age, an intraperitoneal glucose tolerance test was performed, blood and organs collected.
Results: HFD-fed dams switched to chow in pregnancy had less gestational weight gain compared to control (P<0.05), though glucose tolerance remained impaired (P<0.05). At weaning, body weights of HFD-fed offspring were lower in mice whose mothers underwent preconception diet modification, regardless of mode, compared to offspring of HFD-fed mothers (P<0.05). At week 12, offspring of HFD-fed dams, regardless of pre-pregnancy liraglutide, had greater body weight and greater white adipose tissue mass, impaired glucose tolerance, and higher serum triacylglyceride levels, compared to offspring of lean mothers (P<0.005, P<0.001, P<0.05, P< 0.05 respectively). Offspring of mothers with pre- or post-conception switch in diet had normal glucose tolerance.
Conclusion: Maternal weight loss by diet modulation was most successful in improving glucose tolerance and body weight in offspring when instigated before conception. Preconception liraglutide without diet change did not improve offspring glucose tolerance. These findings suggest the preconception period is critical for foetal programming.