Degree

Doctor of Philosophy (PhD)

Department

Biological Science

Document Type

Dissertation

Abstract

Adipose tissue is a dynamic endocrine organ that contains both the problem and the solution to discovering new therapies for individuals with obesity. Excessive adipose tissue disrupts energy balance and causes a host of comorbidities like insulin resistance and hypertension. On the other hand, adipose tissue is essential for life. During periods of energy demand, sympathetic nerve activity in brown and white adipose tissue stimulates thermogenesis and lipolysis; both of which decrease body weight and improve metabolic health. Therefore, comprehensive insight into the organization of sympathetic innervation and how it communicates with adipocytes is critical in order to utilize its capacity to reduce body weight and improve metabolic health. Recent literature enhances the confusion about the neuronal origin of postganglionic sympathetic innervation, and little is known about preganglionic inputs. Here we inject a retrograde transsynaptic tracer, pseudorabies virus (PRV), into the right interscapular brown adipose tissue (iBAT) pad and the inguinal WAT (iWAT) pad of mice to label pre- and postganglionic neurons that innervate iBAT and iWAT, respectively. To ensure a thorough investigation into the sympathetic structures, we established a whole-body tissue clearance method combined with a double immunohistological detection to identify sympathetic nerves and adipose tissue-related sympathetic circuits. Three-dimensional images generated with light sheet microscopy allowed for an unprecedented view of abdominal sympathetic structures. iBAT postganglionic innervation was found to be restricted to sympathetic chain ganglia (SChG) from the stellate ganglion (SG) to thoracic ganglion 5 (T5), while preganglionic innervation was found from T1-T5. iWAT postganglionic innervation was found at T12 to lumbar ganglion 1 (L1), while preganglionic innervation was found from T7-T10. Importantly, PRV labeling was not identified in the prevertebral celiac ganglia. These novel observations demonstrate that the population of pre- and postganglionic neurons innervating iBAT and iWAT are distinct from one another.

Date

7-9-2020

Committee Chair

Muenzberg-Gruening, Heike

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