Obesity together with insulin resistance promotes multiple metabolic abnormalities and is strongly associated with increased risk of chronic disease including type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic kidney disease (CKD). The incidence of obesity is rising and affects all different stages of the lifespan. Importantly, obesity in women of reproductive has potential ramifications for offspring health. Maternal obesity is known to influence offspring development of obesity, T2D and CVD. In contrast, the relationship between maternal obesity and CKD has been less clearly defined. This thesis aims to determine whether maternal obesity increases offspring risk of CKD. Rodent models of maternal obesity were employed by feeding dams a high fat diet (HFD) for 6 weeks prior to mating, during gestation and lactation. At Day 20, there was evidence of renal inflammation and oxidative stress in the kidneys of rat offspring and the nuclear hormone receptor Farnesoid X receptor (FXR) was pathogenically implicated. At postnatal Week 9, the kidneys of rat offspring of obese mothers demonstrated increased markers of inflammation, oxidative stress and fibrosis, exacerbated by HFD-feeding in the offspring. The glucose-like peptide-1 (GLP-1) analogue, Exendin-4, ameliorated the negative renal effects of maternal. GLP-1 analogues may be useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring. Consistent with the metabolic effects observed in the rat, mouse offspring of obese mothers at postnatal Week 32 had increased fat deposition, insulin resistance and impaired glucose tolerance and renal pathology. Furthermore, postnatal feeding of HFD in offspring augmented these effects. Offspring of obese mothers were more prone to renal damage when an additional insult, such as streptozotocin-induced diabetes, was imposed. However, offspring obesity induced by HFD was the strongest predictor of weight gain, glucose intolerance, albuminuria and renal damage, which appeared to overpower the effect of maternal obesity. This thesis suggests that developmental programming resulting from in utero exposure to maternal obesity predisposes offspring towards CKD. Foetal exposure to maternal obesity should be considered as a significant risk factor for CKD
