The Effects of Western-diet, Palmitate, and TNFα on Hypothalamic Circadian Rhythms, NPY Expression, Neuroinflammation, and Cellular Insulin Sensitivity
Year: 2019
Type: dissertation
Abstract: Western diets are typically high in saturated fats and sugar and thus induce weight gain, alter circadian rhythms, increase inflammatory cytokines, and alter whole body glucose homeostasis. However, the links between circadian and hypothalamic energy homeostasis remain undefined. In C57BL/6-J mice, the Western diet significantly decreased peak food consumption, with a concomitant decrease in hypothalamic expression of orexigenic neuropeptides. In vitro, palmitate induced neuropeptide Y (Npy) and Bmal1, and reduced Per2 expression in a BMAL1-dependent manner. TNFα, a palmitate-induced cytokine, activated neuroinflammatory cytokine expression and reduced insulin sensitivity in NPY-expressing neurons. Cellular neuroinflammation occurred through the canonical IKK-β/NF-κB pathway. The induction of insulin resistance by TNFα was maintained after with IKK-β/NF-κB pathway inhibition, indicating that TNFα-mediated neuroinflammation and insulin resistance occurs via distinct mechanisms. With this study, I provide insight into the mechanistic link between fatty acid-induced feeding-related neuropeptide dysregulation, inflammatory activation, circadian rhythms, and insulin resistance.
Source: TSpace (University of Toronto)
Author: Matthew N. Clemenzi
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3137789656