Background/aim:
Maternal obesity adversely impacts metabolic health in mothers and offspring. Maternal complications include diabetes and chronic kidney disease(CKD). Our previous work showed that offspring have increased risks of obesity and CKD. While pre-pregnancy weight optimisation is advocated, evidence of benefits for mother and offspring are lacking. We aimed to determine if weight loss prior to pregnancy, by administration of liraglutide, improves maternal and offspring kidney health in obese mothers and the 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.,for4weeks) or switched to chow, to induce pre-conception weight loss. Maternal anthropometry and glucose tolerance were measured before and after intervention, and at late gestation. Pregnant dams were culled at gestational day 18-20 with blood and kidney harvested, or allowed to deliver their offspring. Offspring anthropometry, and glucose tolerance were assessed at postnatal week 12 after either HFD or chow feeding. ELISA, Immunohistochemistry and RT-PCR were used to measure kidney metabolic and inflammatory markers.
Results:
Obese mothers had reduced glucose tolerance compared to chow-fed mothers(p<0.0001), and higher expression of renal metabolic and inflammatory markers in late gestation(FAS <0.05, TGFb <0.05). Liraglutide lowered body weight, improving glucose tolerance prior to conception(p<0.001). Markers of kidney damage (albuminuria, fibronectin, serum creatinine) were reduced in obese mothers administered liraglutide(p<0.05). Liraglutide treated mothers exhibited greater gestational weight gain than obese mice given vehicle control(P<0.001). Oxidative stress were similar in obese mothers with or without preconception weight loss with liraglutide(8-OHdg,MnSOD,PGC1α). Kidney metabolic and inflammatory markers(MCP-1,FAS,SREBP) were altered in HFD-fed offspring of obese mothers administered liraglutide(p<0.05).
Conclusions:
Preconception weight loss with liraglutide improves kidney and metabolic outcomes in mothers and the offspring. Therefore, obese women should be targeted for pre-conception weight loss to improve intergenerational metabolic health.