Current work and interests

The aim of my research is to find out how obesity during pregnancy alters development of the offspring’s hypothalamus- an area of the brain that is essential for regulating food intake- and leads to an increased obesity risk in these individuals.

Background and experience

I completed my BSc. in Physiology at the University of Liverpool in 2009, before moving to the University of Bristol for a Ph.D. studying how the hypothalamus senses the nutrient status in the rest of the body. During my Ph.D., I became fascinated by how these same hypothalamic pathways might be altered in individuals exposed to maternal obesity. In 2014, I obtained a Sir Henry Wellcome Fellowship to work with Professor Susan Ozanne (IMS-MRL) and Dr Sebastien Bouret (then UCSC) to investigate this further.

Working at the IMS-MRL

My research will help us understand the molecular mechanisms that mediate the effects of maternal obesity on offspring hypothalamic development and function. One of the main factors altered in both the mother and baby during an obese pregnancy compared to a lean pregnancy is insulin. I aim to define how the increased insulin levels in an obese pregnancy alter hypothalamic development. In addition to direct effects on neuro-development insulin can regulate expression of miRNAs, which are small RNAs that control gene and protein expression. Therefore, insulin-mediated changes in miRNA levels are a likely cause of the lasting changes in gene expression in the hypothalamus that lead to feeding pathway dysfunction and thus obesity.

Working in a mouse model, I will be using state of the art techniques to experimentally manipulate insulin and miRNAs in the fetal brain so that we can examine the consequences for hypothalamic development and feeding behaviour when these factors are altered, as they are in an obese pregnancy. I will also be using more translatable interventions strategies that will correct maternal and fetal insulin levels in a more physiological way- such as exercise or clinically relevant drugs- to confirm our findings from the fetal brain manipulations.

This research will address an important gap in our knowledge of how obesity during pregnancy affects the long- term health of offspring. This will enable us to better advise obese individuals during pregnancy and develop intervention strategies to stop the inter-generational transmission of obesity risk.

Awards

I have recently been awarded a Dorothy Hodgkin Fellowship from the Royal Society to start building an independent research career at the IMS.

Sir Henry Wellcome Post-doctoral Fellowship (2015-2020).

Selected publications

• Dearden L, Buller S, Furigo IC, Fernandez-Twinn DS, Ozanne SE (2020) Maternal obesity causes fetal hypothalamic insulin resistance and disrupts development of hypothalamic feeding pathways. Mol Metab. 42:101079
• Dearden L, Bouret SG, Ozanne SE (2021) Nutritional and developmental programming effects of insulin. J Neuroendocrinol. 2021 33(4)
• Dearden L, Berends LM, Tung YC, Voshol P, Fernandez-Twinn DS & Ozanne SE (2018) Postnatal catch-up growth programs central and peripheral insulin resistance in male mice. Diabetologia 61 (10): 2225-2234
• Dearden L and Ozanne SE (2015) Early life origins of metabolic disease: developmental programming of hypothalamic pathways controlling energy homeostasis. Front Neuroendocrinol. 39:3-16
• Dearden L and Balthasar N (2014) Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and physiological responses to maternal high-fat diet feeding. Endocrinology 155 (6): 2144-54