Introduction: Epidemiological evidence suggests that a poor diet during pregnancy leads to offspring with higher risk of chronic diseases in adulthood. Our previous work in sheep showed that mild protein-energy malnutrition in early gestation results in decreased insulin signalling in the liver, and changes in vascular endothelial growth factor (VEGF) in the kidney. The current study explored whether these changes are generalised phenomena, or organ-specific.
Methods: Pregnant ewes were fed either a control diet providing adequate dietary protein (control, C; n=15), or a low protein diet (50% protein restriction) during early pregnancy (065 days of a 147 day gestation; low protein, LP, n=16). Fetuses were killed at day 65 gestation, or carried to term and killed in adulthood at two years of age. Organs were snap frozen in liquid nitrogen, or preserved in 4% paraformaldehyde. The mRNA was measured using quantitative PCR, and protein levels assessed using immunohistochemical techniques.
Results: In the fetal kidney VEGF mRNA and protein was reduced by 3040% in LP vs controls, but as adults the reverse was true. In contrast, in the fetal liver, VEGF mRNA was increased threefold in LP fetuses vs controls, and was not different between groups in the adults. However, as adults, the LP exposed animals had hepatic insulin resistance, and down-regulated insulin-sensitive genes. In the adult kidneys, at this stage there were no significant reductions in the insulin pathway genes in the LP group.
Conclusions: A low protein diet leads to hepatic insulin resistance and effects on VEGF in the kidney. However, these effects are organ-specific and do not translate to other organs.
Declaration of funding: This work was supported by a Society for Endocrinology Early Career Grant.