White adipose tissue control by the peripheral nervous system

White adipose tissue (WAT) accounts for 20-25% of total body mass in healthy humans and is one of the largest endocrine tissues in the body, controlling whole body energy balance and appetite. Adipocytes play a dynamic role in storing excess dietary energy in the form of triglycerides (lipogenesis) and releasing energy from stored triglycerides (lipolysis) during fasting and exercise. The balance between lipogenesis and lipolysis is tightly controlled by circulating hormones including insulin, leptin and ghrelin, and the molecular mechanisms behind this regulation is fairly well understood. Though WAT plays a pivotal role in the physiological control of homeostasis and metabolic heath, the molecular mechanisms underpinning innervation of WAT by the peripheral nervous system remain unclear. Many body tissues are under the control of the peripheral nervous system including efferent innervation (from central nervous system [CNS] to tissue) and afferent innervation (from tissue to CNS). Some information regarding efferent pathways in WAT are understood and under pharmacological exploitation for modulation of body metabolism.

This project will investigate the role of extracellular ATP acting as a neurotransmitter at purinergic receptors (P2X and P2Y) in efferent and afferent communication with mouse white adipose tissue. The project will employ a combination of confocal microscopy and ex vivo physiology to investigate the role of ATP in efferent regulation of lipolysis, and Ca2+ imaging and electrophysiology in identified afferent pathways in isolated sensory neurons.