Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2023

Maternal markers of kidney damage are improved with preconception weight loss, but not gestational weight modulation, in a mouse model of maternal obesity (98113)

Natassia Rodrigo 1 2 3 , Hui Chen 4 , Carol Pollock 2 3 5 , Sarah Glastras 1 2 3
  1. Endocrinology, Royal North Shore Hospital, St Leonards, NSW, Australia
  2. University of Sydney, Sydney, NSW, Australia
  3. Kolling Institute of Medical Researh, Sydney, NSW, Australia
  4. University of Technology, Sydney, Sydney, NSW, Australia
  5. Renal Department, Royal North Shore Hospital, Sydney, NSW, Australia

Maternal obesity poses significant risk to mother and baby and contributes to increased rates of gestational diabetes and preeclampsia. Further, obesity predisposes to chronic kidney disease. No studies have addressed whether preconception maternal weight loss, rather than gestational weight loss, can reduce kidney damage in mothers with obesity. We aimed to determine if weight loss prior to pregnancy, either with diet modification or intervention with liraglutide, restores normal kidney structure and function, compared to gestational weight loss.

Methods:

Female C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks versus chow diet as control. In the obese dams, diet modification (switch to chow diet) or liraglutide treatment (0.3mg/kg s.c. for 4 weeks) was used to induce pre-conceptional weight loss. Gestational intervention was induced with diet modification once pregnancy was confirmed. Mice were sacrificed in the preconception period or at gestational Day 18. Maternal anthropometry was measured in preconception and late gestation. Urine, blood and kidneys were collected. Immunohistochemistry, ELISA, Western blotting, and real-time PCR were used to measure renal inflammation, fibrosis, oxidative stress and metabolic function.

Results:

Preconception intervention with liraglutide or diet reduced urine albumin:creatinine ratios(UACR)(p<0.005), which was sustained into pregnancy(p<0.005).  Liraglutide-induced weight loss showed better preconception improvement in inflammatory and oxidative stress kidney markers (e.g., MNSOD, eNOS,8-OHDG, PGC1α) than diet change alone(p<0.005), a distinction which was lost by late gestation. Renal metabolic markers were also improved (FAS, InR, PPARα, p<0.05) Renal fibrotic markers were reduced by preconception weight loss (CollagenIV, fibronectin, p<0.0005). Gestational diet change showed modest improvement in UACR (p<0.05), inflammation and oxidative stress(p<0.05) but no improvement in fibrotic or metabolic markers.

Conclusions:

Preconception weight reduction improves maternal renal health prior to pregnancy, with sustained benefit into pregnancy. Gestational weight intervention, while mildly beneficial, appeared to be too late to facilitate global improvements in renal health.