Author ORCID Identifier
Date of Award
Doctor of Philosophy (PhD)
The rising prevalence of obesity poses a significant public health challenge, with profound implications for metabolic disorders and associated health risks. In the United States, approximately 40% of adults are considered obese. Obesity is caused by a prolonged increase in energy intake coupled with a decrease in energy expenditure. Adipose tissue is a key player in the regulation of energy balance. There are three different types of adipocytes that compose the adipose tissue organ. White adipocytes are specialized for energy storage in the form of triglycerides while brown and beige adipocytes excel in energy dissipation via thermogenesis. Brown adipocytes are located in anatomically defined areas such as the intrascapular region (iBAT) and beige adipocytes are dispersed in clusters within larger white adipose tissue depots. Adipose tissue is densely innervated by the sympathetic nervous system (SNS), which is indispensable in the induction of adipocyte thermogenesis and lipolysis. The SNS responds to cold stimulus and excessive feeding by releasing catecholamines, which in turn activate brown/beige adipocyte thermogenesis and lipolysis. The activation of brown and beige adipocyte thermogenesis increases energy expenditure and promotes weight loss. Metabolic research has primarily focused on the investigation of neuroendocrine pathways regulating SNS activity. Hence, there exists a significant gap in knowledge regarding the role of SNS-targeted tissues, such as adipose tissue, in the regulation of SNS activation and development. The adipose tissue-derived hormone, leptin, has emerged not just as a master regulator of energy homeostasis, but also potent modulator of nervous system development. In this study, we utilize a knockout mouse model with sympathetic neuron specific deletion of the leptin receptor and additional transgenic mouse models to investigate the role of peripheral sympathetic leptin signaling in whole-body energy homeostasis. We have discovered a novel mechanism by which sympathetic leptin signaling regulates SNS innervation of adipose tissue and diet-induced thermogenesis.
Silva, Felipe C., "Peripheral Sympathetic Leptin Receptor Signaling Regulates Sympathetic Innervation of White Adipose Tissue and Diet-Induced Thermogenesis." Dissertation, Georgia State University, 2023.
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