Obesity is one of the most significant public health challenges of this century. Its global prevalence continues to increase dramatically, particularly among children in the last years. Obesity has been recognised by the World Health Organization (WHO) as a worldwide epidemic, and the European Association for the Study of Diabetes (EASD) has recognised the prevention and treatment of obesity as “the most important public health issue worldwide”. Obesity results in mechanical and psychological problems, however, the major concern it is that has been associated with several chronic diseases such as diabetes, heart disease, high blood pressure, stroke, fatty liver, and cancer, as well as a increased risk of severe illness from COVID-19. Commonly, obesity is caused by excess food intake relative to energy loss via our physical activity and our body metabolic processes. However, the etiology of obesity is multifactorial and extraordinarily complex. Physiological, behavioural and genetic factors play a crucial role in the etiology of this disease. No single cause has been assigned to obesity, so the study of each implicated components is vital for a successful approach against this global problem.
Globally, approximately 1.5 billion adults are overweight, and among them, 200 million men and about 300 million women are obese (data from WHO). Obesity is not just associated with higher mortality or worse life quality, but also has a huge impact on society in terms of healthcare costs linked to the treatment of this pathology and its complications. Although the main option to treat obesity is lifestyle modifications, this result is unsuccessful over the long term; thus, the addition of pharmacotherapy is considered as another approach to treat obesity.
The excess of energy in an organism is accumulated in the form of fat. The optimal maintenance of body weight and fat mass is a complex biological process that depends on the brain´s capacity to receive, integrate, and send a wide range of signals which it must adjust and keep balanced via the peripheral nervous system. Within the peripheral nervous system, the sympathetic nervous system (SNS) is strongly linked to obesity. Thus, several models of obesity have shown low levels of activity in SNS, suggesting that its low activity predisposes to and is associated with obesity. SNS plays a crucial role in the regulation of several metabolic processes in fat, including lipolysis, number of adipocytes and secretion of hormones. However, simultaneously, the SNS is implicated in other essential metabolic processes, including cardiovascular function. The general objective of this project was to better understand the mechanisms that underlie obesity related to the role of the SNS; more specifically, we tried to identify drug targets in SNS neurons innervating exclusively fat, which could be suitable for an anti-obesity therapy avoiding any side effect that could have consequences in key organs.
