Biomedical Sciences ETDs

Publication Date

Spring 6-6-2023

Abstract

Lipids are one of life’s four main macromolecules and provide essential functions to cells, as they serve as building blocks of cellular membranes, mediate cell signaling, and are a critical energy source. Within cells, esterified fatty acids aggregate into lipid droplets in the form of triglycerides, consisting of a neutral lipid core surrounded by a phospholipid monolayer decorated with various proteins.

The degradation of lipid droplets and mobilization of lipids occurs through lipolysis, a process that hydrolyzes a molecule of triglyceride into a glycerol and three fatty acids. Emerging evidence demonstrates the involvement of a selective form of autophagy in lipolysis with two similar—but distinct—mechanisms. The first is lipophagy, in which autophagosomes trap lipid droplets and then fuse with lysosomes. The second is microlipophagy, which occurs when lysosomes directly engulf lipid droplets. Because the homeostatic balance of lipids is critical to proper cellular functions, and whose impairment leads to disease, it is essential to understand how lipid turnover is maintained. The process of microlipophagy has only recently been described, and many features of its regulation are still poorly understood. Our recent study showed that inhibiting mammalian target of rapamycin complex 1 (mTORC1) pathway by depletion of Raptor in adipocytes led to an influx of lysosomes and accumulation of lipid droplets within lysosome. Here, we expand on these previous findings and explore whether lysosome induction possibly pertaining to microlipophagy is regulated by mTORC1 or beta adrenergic receptor (BAR), two pathways that are involved in regulating lipid droplet breakdown in adipocytes. We were able to conclude that more lysosomes were induced when BARs are activated rather than by mTORC1 inhibition in primary differentiated adipocytes. Thus, BAR activation rather than mTORC1 may be the primary regulator of microlipophagy. This research could help elucidate the dynamics of lipid droplet turnover which is pivotal to developing novel treatments for metabolic diseases specifically obesity.

Keywords

microlipophagy, adipocytes, mTOR

Document Type

Thesis

Language

English

First Committee Member (Chair)

Curt Hines

Second Committee Member

Meilian Liu

Third Committee Member

Jing Pu

Fourth Committee Member

Xiang Xue

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