Does maternal diet during pregnancy advance ageing of nutrient sensing pathways in the offspring brain?

Summary

Maternal diet during pregnancy is known to have long-term effects on the cardio-metabolic health of the offspring, including increased risk of obesity. Our previous studies in animal models have shown that alterations in maternal diet programs accelerated ageing phenotypes in peripheral tissues and contributes to the development of metabolic disease.

Weight gain in offspring exposed to maternal over-nutrition is caused by hyperphagia- implicating altered function of hypothalamic energy homeostatic pathways as an underlying cause - but whether the hypothalamus undergoes accelerated ageing as a result of exposure to maternal over-nutrition is unknown.

Central insulin resistance is a hallmark of both ageing and advanced obesity phenotypes, indeed brain insulin resistance has been proposed as one of the drivers of age associated increases in type 2 diabetes incidence. We have previously shown that intra-uterine growth restriction resulting from maternal under-nutrition programs accelerated central insulin resistance in male animals, which may contribute to the development of metabolic phenotypes.

Project aims

This project will investigate the consequences of an obese pregnancy environment for hypothalamic insulin sensing across the lifecourse, and the molecular mechanisms underlying changes in insulin sensitivity. Male and female brains have inherent differences in insulin sensitivity so it is important to conduct these studies in both sexes. This project will involve in vivo work with an animal model and physiological studies of the animals metabolic health.

This will be combined with molecular techniques to examine changes in the anatomy of the brain, and next generation sequencing to identify transcriptomic differences. This research will aid the development of sex- specific interventions that promote healthy ageing and stop the inter-generational transmission of obesity risk.

Contact details

Dr Laura Dearden - ld454@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD