The aim of our 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 increased food intake and obesity later in life.
Our research will help us understand the molecular mechanisms that mediate the effects of maternal obesity on offspring hypothalamic development and function. If we understand the mechanisms at play during a pregnancy with obesity, we can try and intervene in the inter-generational transmission of obesity risk. We are particularly interested in the role of insulin, as this is one of the main factors altered in both the mother and baby during a pregnancy complicated by obesity. We are using mouse models to define how the increased insulin levels in a pregnancy with obesity alters hypothalamic development in the baby. In addition to direct effects on brain development insulin can regulate expression of miRNAs, which are small RNAs that control gene and protein expression. 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, we can experimentally manipulate insulin and miRNAs in the fetal brain so that we can examine the consequences for hypothalamic development and later feeding behaviour when these factors are altered (as they are in a pregnancy with obesity). We are also investigating translatable interventions strategies that will correct maternal and fetal insulin levels in a more physiological way- such as exercise, or drugs that are given to women with gestational diabetes.
This research will address an important gap in our knowledge of how it is that obesity during pregnancy affects the long- term metabolic health of offspring. It is currently not feasible to ensure all women enter pregnancy with a healthy BMI, so interventions to improve the health of offspring exposed to obesity in pregnancy may need to occur after birth. An understanding of the mechanisms at play during pregnancy will enable us to a) better advise individuals who have obesity during pregnancy and b) develop intervention strategies to stop the inter-generational transmission of obesity risk.
I hold a Dorothy Hodgkin Fellowship from the Royal Society.
I was awarded the 2023 Rank prize New Lecturer Award in Nutrition.
I previously held a Sir Henry Wellcome Post-doctoral Fellowship (2015-2020).
- Furigo IC, Pantaleão LC, de Almeida-Faria JF, Kentistou KA, Carreira MV, Ong KK, Perry JRB, Donato Jr J, Dearden L*, Ozanne SE* Maternal obesity programs hypothalamic miR-505-5p expression in mouse offspring and impacts hypothalamic fatty acid sensing. https://www.biorxiv.org/content/10.1101/2022.06.01.494310v1 * Joint senior authors
- Furigo IC and Dearden L (2022) Mechanisms mediating the impact of maternal obesity on offspring hypothalamic development and function. Front Endocrinol. 22;13:1078955.
- 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, 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 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