Exposure to excess nutrition in utero and in early postnatal life is associated with adverse consequences for the offspring including diabetes, hypertension, dyslipidaemia, cardiovascular and chronic kidney disease

Aim: We hypothesized that exposure to overnutrition in utero and early postnatal life is associated with changes in metabolic and pro-inflammatory markers within the kidney of rat offspring.

Method:  Female rats were continuously fed either normal or high-fat diet (HFD) before pregnancy and the male offspring's kidneys examined at Day 1, Day 20 or Week 13. Animals examined at Week 13 were exposed to a normal diet or HFD from Day 20. The anthropometric and hormonal measures of the pups were recorded. Gene expression of profibrotic, proinflammatory and metabolic markers was measured by RT-PCR. Western blotting and immunohistochemistry were utilized to confirm findings.

Results: Compared to offspring of lean mothers, offspring of obese mothers had increased body weight, triglycerides, and impaired glucose tolerance (IGT) at day 20, though the effect was ameliorated by week 13 if they were fed normal diet. Offspring born to obese mothers and fed HFD post-weaning had increased body weight and IGT at Week 13. Leptin, ghrelin, GLP-1, and glucagon were increased in offspring of obese mothers at Week 13. Renal gene expression of inflammatory markers MCP-1 and TGF-β1 were increased in offspring of obese mothers at Day 1. They also had reduced renal FXR mRNA expression from Day 1 -Week 13. Offspring fed HFD had increased renal fatty acid synthase levels at Week 13 regardless of maternal group.

Conclusions: Exposure to maternal overnutrition is associated with changes in inflammatory and metabolic markers in the kidneys of offspring at birth. Ongoing exposure to HFD in adult life results in changes in renal fatty acid and lipid metabolism. FXR may be an important modulator of this effect.