Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

Final Activity Report Summary - OBESITY&HYPERTENSION (Identifying key neuronal pathways mediating melanocortin's effects on cardiovascular function)

Recent population statistics demonstrate drastically increased risk of cardiovascular death with obesity. To develop effective therapies, we need to understand the pathways regulating body weight homeostasis and cardiovascular function. Obesity results from an imbalance between energy intake and spending. Particular brain structures sense the body's energy status and through a sophisticated cascade of events, elicit an appropriate response to the body. Recent research has unravelled some of these pathways, but the exact mechanisms remain unclear. One of the central genes involved is the melanocortin-4-receptor (MC4R) and we aimed to define and detail its role in the regulation of obesity-induced cardiovascular disease.

Data from these studies suggest that MC4Rs in a particular area of the hypothalamus, the paraventricular hypothalamus (PVH), are key contributors to melanocortin-mediated cardiovascular effects. Furthermore our results suggest that MC4Rs in the PVH may mediate their effects by increasing sympathetic tone onto the cardiovascular system. There is significant interest from the pharmaceutical industry to develop MC4R agonists as potential food intake reducing agents. However, side effects due to sympathetic activation after MC4R engagement are highly likely and our data help to understand where these effects are mediated.

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United Kingdom