Advisory Committee Chair
Maria Grant
Document Type
Dissertation
Date of Award
2024
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
The sympathetic nervous system is a key regulator of energy homeostasis, in part, through the control of white adipose tissue lipolysis. Sympathetic nerves modulate adipose tissue physiology through the release of catecholamines, particularly norepinephrine, onto alpha- and beta-adrenergic receptors (a-AR; B-AR). Lipolysis refers to the breakdown of triglycerides into glycerol and free fatty acids, often in response to activation of B2/3-AR. Beta adrenergic activation of lipolysis is widely known to be impaired in patients with metabolic syndrome and animal models thereof (catecholamine resistance). Recent studies have demonstrated that catecholamine regulation of adipokine release is also disrupted, suggesting that catecholamine resistance may contribute to the reduced levels of insulin sensitizing hormones such as adiponectin observed in metabolic syndrome. Unsurprisingly, catecholamine resistance is a prospectively identified risk factor for development of glucose intolerance and type 2 diabetes, making further study of considerable value to preventative medicine. Remarkably, in the decades since catecholamine resistance was first identified, comparatively little work has examined whether it might be mechanistically driven by excessive receptor stimulation. When receptors are chronically stimulated by their ligands, they often undergo desensitization and downregulation. Much data show that sympathetic nerve activity is elevated in metabolic syndrome, a phenomenon which has been widely explored in clinical research, particularly in areas such as hypertension. This present body of work fills two key gaps in this area by 1) assessing the physiology and neurochemistry of sympathetic nerves in adipose tissue under normal diet and high fat diet (in both visceral and subcutaneous fat) and 2) testing the hypothesis that central manipulations which modulate sympathetic nerve activity could recapitulate catecholamine resistance in animal models.
Recommended Citation
Rosencrans, Robert Follett, "Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome" (2024). All ETDs from UAB. 3909.
https://digitalcommons.library.uab.edu/etd-collection/3909
