Smelling yourself thin – Olfaction to treat obesity

Obesity and overweight are major health concerns and a burden to public health in Australia, affecting 2 in 3 adults (12.5 million), and 1 in 4 children (1.2 million). To address this and 22 associated comorbidities, it’s crucial to understand the brain mechanisms driving overconsumption and obesity. Human GWAS studies show that obesity has a strong genetic component associated with the neural control of feeding. While previous research focused on how hypothalamic or brainstem mechanisms regulate food intake and body weight, studies in humans show the cognitive processing of sensory cues, which predict a calorie-rich environment, plays an important role in the development of obesity. Thus, understanding how brain regions integrate internal and external sources of metabolic information is essential for therapeutic development. Our senses, particularly smell, play a crucial role in assessing whether food is available, palatable, or potentially toxic. Surprisingly, various pathological conditions like metabolic diseases, such as obesity, coincide with impaired olfactory function, but the link remains unclear. This project aims to investigate how brain regions governing smell and metabolism interact. Recent research suggests humans possess a more developed sense of smell than previously believed. While not used for foraging like animals, olfaction is crucial for food assessment, preference and pleasure. The loss of smell (anosmia), such as in response to head trauma, increases the risks of food poisoning, malnutrition, and decreases enjoyment of food. This emphasizes the need to explore how olfaction affects feeding behaviours and metabolic health. Smell information is first processed in the brain by the olfactory bulb (OB), an underappreciated neuroendocrine centre that has high expression of metabolic hormone receptors, such as insulin (IR), leptin (LepR) and ghrelin (GHSR). Transport of these key metabolic hormones into the OB is faster than anywhere else in the brain, rendering the OB highly susceptible to metabolic regulation. How the OB integrates metabolic hormone signals and communicates with circuits controlling feeding behaviour and metabolism is unknown. AIMS: 1. Assess the necessity of hormone receptors in the OB on feeding behaviour and metabolism 2. Examine the role of hormone receptors in the OB on homeostatic feeding circuits