Identification of hypothalamic neural circuits regulating glucose and energy homeostasis

Abstract

Diabetes and obesity are among the most common and costly health issues facing modern humans. The World Health Organization (WHO) estimates that obesity rates have tripled in the last 50 years: as of 2016, nearly 40% of adults are overweight, and 13% are obese. Given the strong association between obesity and type 2 diabetes (T2D), a compelling need exists for improved understanding of their pathophysiology. Accumulating evidence shows that the brain plays a critical role in the regulation of energy and glucose homeostasis. However, the underlying neurocircuitry by which the brain regulates energy balance and glycemia is narrowly understood, due to the exceedingly complex and highly interconnected nature of mammalian neurocircuitry. In this dissertation, I will discuss how, using a combination of engineered mouse models and genetically encoded tools, along with sophisticated metabolic phenotyping, we advanced our understanding of brain neurocircuits regulating energy homeostasis.