Date of Award

5-10-2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Bingzhong Xue

Second Advisor

Aaron Roseberry

Third Advisor

Ruth Harris

Abstract

More than 30% of the population suffers from obesity, which increases the risk of death and secondary health problems. Body fat [white adipose tissue (WAT) and brown adipose tissue (BAT)] are innervated and regulated by the sympathetic nervous system (SNS). WAT stores energy, while BAT generates heat for thermoregulation. Fat also has sensory innervations, but the roles of sensory nerves are still being elucidated. Hence, understanding the neuroanatomy of the SNS innervations of fat and the neural regulation of fat metabolism will be valuable for advancing obesity treatment. Using trans-synaptic tract tracers with unique fluorescent proteins, we defined and compared the SNS innervations of visceral fat [mesenteric WAT (MWAT)] and subcutaneous fat [inguinal WAT (IWAT)] and of IWAT and interscapular BAT (IBAT) in Siberian hamsters. MWAT and IWAT have moderately shared SNS innervations within the hindbrain, but separate SNS innervations in rostral regions. In contrast, IWAT and IBAT have relatively separate SNS circuitries throughout the brain yet some overlap in SNS nuclei known to regulate thermogenesis. We tested for the presence of functional coordination between IWAT and IBAT defined by overlap in IWAT SNS and IBAT SNS innervations. When IBAT function was impaired by SNS denervation, IWAT SNS drive, thermogenic activity, and beige adipocyte recruitment increased in cold exposed hamsters likely through coordination with IWAT SNS pathways. Conversely, we found that only SNS drive to IWAT increased during acute food deprivation suggesting that populations of SNS neurons singly innervating each fat depot may contribute to differential SNS drive to fat. Lastly, we demonstrated that IWAT sensory nerves mediate the functional coordination between IWAT and IBAT and the regulation of SNS drive to fat. The absence of IWAT sensory feedback via sensory denervation differentially decreased SNS drive to IBAT and IWAT itself, but not to MWAT, retroperitoneal WAT, and epididymal WAT in cold exposed hamsters. Collectively, the studies in this dissertation provide neuroanatomical evidence of separate and shared SNS brain sites likely receiving sensory signaling and regulating SNS drive to fat, and direct evidence of the roles of SNS and sensory nerves innervating fat to energetic homeostasis and thermoregulation.

Available for download on Sunday, April 22, 2018

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