Exposure to maternal obesity in utero affects gene expression in offspring’s kidneys (#298)
Obesity affects almost one quarter of the adult population and is increasing rapidly among women of childbearing age. Mounting evidence suggests that maternal obesity ‘programs’ the offspring to be prone to obesity, dysglycaemia, diabetes, hypertension and CKD. Recently it has been reported that children of obese mothers have a 22% increased risk of developing CKD. Aim: We aimed to study the effect of maternal obesity on mRNA expression in the offspring’s kidneys in a rat model of obesity. Methods: Pregnant female rats were fed either normal or high-fat diet and their offspring’s kidneys examined at Day 1 (birth) or Day 21 (weaning) of postnatal life. Their kidneys were weighed and snap frozen for protein and mRNA extraction. The pups’ anthropometric measures, plasma triglycerides and glucose/insulin levels were recorded at Day 21. mRNA was extracted and gene expression of profibrotic factors (TGFbeta, CTGF, PAI-1), proinflammatory cytokines (TNF, IL-6 and MCP-1), and metabolic markers (FXR, PPAR, SREBP) was measured by real time PCR. Results: Offspring from obese rats displayed increased body weight, fat and kidney mass, blood triglycerides, and glucose intolerance compared with those from lean rats. mRNA expression of proinflammatory cytokines was increased in offspring of obese mothers compared with lean controls and, in particular, TNFalpha and MCP-1 were higher. There was reduced FXR mRNA expression. Conclusions: Maternal obesity is associated with downregulation of renal FXR and upregulation of MCP1 and TGFß expression in the offspring’s kidneys. This effect was sustained until weaning suggesting offspring exposure to maternal obesity in utero confers an increased risk of kidney disease in the offspring.