Dr Natassia Rodrigo1, A/Prof Hui Chen, Prof Carol Pollock, A/Prof Sarah Glastras
1Kolling Institute Of Medical Research, St leonard, Australia
Background/aims:
Maternal obesity adversely impacts metabolic health in mothers and offspring. Maternal complications include gestational diabetes and preeclampsia. Offspring have increased risks of obesity and diabetes. Evidence demonstrating benefits of pre-conception maternal weight loss is lacking. We aimed to determine if weight loss prior to pregnancy, with liraglutide, improves maternal and offspring metabolic outcomes, and reduces renal inflammation in mothers and offspring.
Methods:
C57BL/6 female mice were fed a high-fat-diet (HFD) for 8 weeks and compared to lean chow-fed controls. HFD-fed dams were administered liraglutide (0.3mg/kg, s.c., for 4weeks) to induce pre-conception weight loss. Pregnancy rates were observed after mating. Maternal anthropometry and glucose tolerance were measured before and after intervention, and at late gestation. 8 pregnant dams per group were culled at gestational day 18-20 with blood and kidney harvested. 8 dams per group delivered their offspring. Offspring anthropometry, and glucose tolerance were assessed at postnatal week 12. Immunohistochemistry and RT-PCR were used to measure kidney metabolic (FAS, SREBP) and inflammatory markers (CD-68,TGF-b).
Results:
HFD-fed dams had reduced glucose tolerance compared to chow-fed dams (p<0.0001), and upregulated expression of metabolic and inflammatory markers in late gestation (eg FAS <0.05, TGFb <0.05). Intervention with liraglutide or diet caused reduced body weight, improved glucose tolerance (both p<0.001), and greater fecundity. Offspring of obese mothers with pre-conception weight loss had lower body weight (p<0.001) and improved glucose tolerance (p<0.01). Kidney metabolic and inflammatory markers (CD-68, FAS) were improved in offspring of liraglutide and diet-switch groups compared to those from HFD-fed mothers.
Conclusions:
Preconception weight loss improves fertility, weight and metabolic outcomes for mother and offspring, with benefits for offspring insulin resistance, kidney inflammation and metabolic markers. This suggests obese women should be targeted for pre-conception weight loss to improve intergenerational renal outcomes.
Biography:
To come.