This is a past event
Rowett Institute Staff Seminar
The increasing rates of obesity and diabetes highlight the need to understand the brain circuits and cellular mechanisms regulating energy balance and glucose homeostasis. Prominent among these is the central leptin- melanocortin system, which includes the pro-opiomelanocortin (POMC) neurons, subsets of which express leptin receptors (LEPRs). Understanding how leptin differentially regulates energy balance versus glucose homeostasis is key for the development of anti-obesity and anti-diabetes therapies. Early observations based on prenatal genetic manipulations led to the widely-held model that LEPR-expressing POMC neurons mediated the metabolic actions of leptin. However, evidence now suggests that these pathways are more complex than originally anticipated. We will first describe some of our recent findings using mouse models that allow temporal, neuron-specific manipulation of genes regulating energy balance and glucose homeostasis. In particular, we will explore the role of a subset of hypothalamic POMC neurons in regulating hepatic glucose metabolism and coordinating metabolic responses to fasting. We will discuss how this model allows us to impair liver metabolism in a temporal manner, allowing us to investigate the pathogenesis of liver insulin resistance. We will also discuss how we harnessed the power of chemogenetics to study how the brain influences the endocrinology of adipose tissue. We will then describe novel exciting data on the role of alpha-melanocyte stimulating hormone (α-MSH), the predicted natural POMC-derived peptide that regulates energy balance. We hope to provide insights into the mechanisms through which the leptin-melanocortin system regulates endocrine, autonomic, and behavioural functions.