Investigating the mechanisms in sympathetic neurons that link sleep to obesity

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Obesity is a major health problem that affects many people worldwide. Unfortunately, there are limited options available to treat obesity, including surgery and medications that suppress appetite, which can be expensive and irreversible. Lifestyle changes and dieting are less expensive but often ineffective because they can lead to a compensatory decrease in energy expenditure, making it difficult to lose weight in the long term. This is because when we reduce our food intake, our body's metabolism adapts to save energy, which can counteract weight loss during dieting.To overcome this problem, we are trying to understand the biological mechanisms behind metabolic adaptation to fasting. One important aspect of this research is to investigate the role of thermogenesis, a process that dissipates energy in the form of heat, and how it is affected by rest and sympathetic neurons. Recent studies in humans and mice have shown that adrenergic beta 2 (adrb2) agonists can boost thermogenesis and energy expenditure, potentially making it easier to lose weight.The goal of this research proposal is to better understand the molecular mechanisms behind metabolic adaptation to fasting and the role of adrb2 in thermogenesis and energy expenditure. The research will use mice to investigate whether adrb2 agonism can mitigate metabolic adaptation to fasting, and whether this effect is dependent on the function of adrb2 in sympathetic neurons that control thermogenic adipose tissue. We also aim to understand whether lack of rest, consequence of sleep deprivation, alters metabolic adaptation to fasting and whether this is connected to lower adrb2 signaling in sympathetic neurons and sympathetic neurodegeneration within thermogenic adipose tissue. We think that this is important to study because it is well known that humans and animals that are sleep deprived gain more weight.Overall, this research aims to provide insights into new approaches to treat obesity that are effective, safe, and affordable. By understanding the molecular mechanisms behind metabolic adaptation to fasting and the role of adrb2 in thermogenesis, other researchers may be able to develop new medications or therapies that can help people lose weight and maintain a healthy lifestyle.