Grant: CIHR Fellowship

How do our bodies know when to stop eating? Why do hot environments or dehydration suppress appetite? Digesting food produces heat, which further increases body temperature. As well, ingesting salt and other nutrients from food increases the concentration of dissolved particles in the blood. As dehydration reduces the amount of water in the body, eating food in this condition further increases the risk of hypernatremia (high sodium levels). Therefore, suppressing appetite can help to prevent the body from dangerously overheating and from worsening the impact of dehydration. The brain constantly monitors changes in temperature and hydration and triggers appropriate responses to restore balance. However, we do not know how the brain regulates feeding in response to heat and dehydration. In this study, I will use cutting-edge techniques to identify the neurons and brain circuits that trigger this response. The physiological control centre of the brain is called the hypothalamus. Within the hypothalamus, the organum vasculosum lamina terminalis (OVLT) region contains specialized neurons that detect temperature and hydration status. These are known to send signals to neurons in another area of the hypothalamus called the paraventricular nucleus (PVN), which controls appetite. I hypothesize that this OVLT-to-PVN neural circuit overrides hunger cues to suppress appetite during overheating and dehydration. This study will identify essential mechanisms by which the brain balances body temperature, hydration, and feeding. As the wiring of the hypothalamus is very similar between rodents and humans, identifying this mechanism in mice will provide an important basis to understand relevant neural circuitry in humans. By studying this system in both sexes, this work will advance our understanding of appetite control in men and women. These results will provide guidance for obesity management and to reduce the negative impact of anorexia associated with heat and dehydration.