Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

GLP-1 receptor agonist Exendin-4 ameliorates oxidative stress and inflammation in offspring’s kidneys induced by maternal obesity  (#187)

Sarah Glastras 1 , Hui Chen 2 , Sonia Saad 1 , Carol Pollock 1
  1. Kolling Institute, RNSH, St Leonards, Sydney
  2. University of Technology, Sydney, NSW, Australia

Maternal obesity increases the risk of chronic disease in the offspring, including diabetes, hypertension and cardiovascular disease. Developmental programming may also affect offspring’s risk of chronic kidney disease. GLP-1 receptor agonists, such as Exendin-4 are effective blood glucose lowering agents and achieve modest weight loss in the setting of type 2 diabetes. They may also have beneficial effects on the kidney. We hypothesized that administration of Exendin 4 (Exd-4) may reduce inflammation and oxidative stress in the kidneys of offspring of obese mothers. 

Method: Female rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation and their offspring were weaned to normal or HFD. The offspring were randomised to Exd-4 or placebo at weaning and their kidneys harvested in early adulthood. 

Results: Offspring of obese mothers fed HFD had increased weight and reduced glucose tolerance. Exd-4 significantly ameliorated these effects. The kidneys of offspring of obese mothers, regardless of postnatal diet, had increased markers of inflammation and oxidative stress. By RT-PCR, mRNA expression of inflammatory markers, monocyte chemoattractant protein -1 (MCP-1) and transforming growth factor was significantly increased in offspring of obese mothers regardless of postnatal diet. Increased MCP-1 mRNA expression in offspring of obese mothers fed HFD was ameliorated by Exd-4. Inducible nitric oxide synthase mRNA, a measure of oxidative stress, was increased by maternal obesity with or without HFD consumption in postnatal life and ameliorated by Exd-4 therapy. Superoxide dismutase (SOD) are enzymes with important anti-oxidant and anti-inflammatory effects. Exd-4 increased SOD activity significantly in the offspring of obese mothers fed normal diet. 

Conclusion: We conclude that maternal obesity affects inflammatory and oxidative stress pathways within offspring’s kidneys.  Exd-4 appears to have a novel protective role against the deleterious renal effects of in utero exposure to maternal obesity.