The Role of Inflammatory Cytokines in the Palmitate-mediated Dysregulation of NPY in Hypothalamic Neurons
Year: 2020
Type: dissertation
Abstract: A contributing factor to the development of obesity is the consumption of saturated fats. Saturated fatty acids such as palmitate dysregulate energy homeostasis by inducing neuroinflammation and orexigenic Npy mRNA in the hypothalamus. Inflammatory analysis identified cytokines that may mediate the induction of Npy mRNA by palmitate: NAMPT/visfatin, MIF, IL-17F and IL-6. With the exception of NAMPT/visfatin, treatment of the NPY/AgRP-expressing mHypoE-46 cell line with the aforementioned cytokines nor conditioned media from palmitate-treated cells were able to directly induce Npy mRNA suggesting a minimal role for cytokines. The monounsaturated fatty acid oleate successfully blunted palmitate-mediate increases in Npy and inflammation in mHypoE-46 cells through mechanisms involving PKA but not SIRT1. This study demonstrates that inflammation and Npy are distinct processes that are induced in a specific population of NPY/AgRP neurons and suggest that differential mechanisms mediate the dysregulatory effects of palmitate in a population-specific manner.
Source: TSpace (University of Toronto)
Author: Tran, Andy Xuan
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7033662329