Novel regulation of hepatic lipid secretion and storage

Lu, Wei

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https://hdl.handle.net/2142/129686 Copy

Description

Title

Novel regulation of hepatic lipid secretion and storage

Author(s)

Lu, Wei

Issue Date

2025-04-15

Director of Research (if dissertation) or Advisor (if thesis)

Wang, Bo

Doctoral Committee Chair(s)

Wang, Bo

Committee Member(s)

• Nelson, Erik
• Spinella, Michael J
• Yang, Jing

Department of Study

Comparative Biosciences

Discipline

VMS - Comparative Biosciences

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Atherosclerosis, VLDL, ApoB lipidation, lipid droplet expansion

Abstract

The liver plays a critical role in lipid homeostasis, where lipids are either secreted as very-low-density lipoproteins (VLDL) or stored in lipid droplets. Previous studies have demonstrated a close relationship between VLDL and lipid droplet metabolism. Impaired VLDL secretion has been associated with increased lipid droplet formation, whereas lipid droplets serve as potential sources of substrates for VLDL secretion. However, the regulatory mechanisms linking these two processes remain poorly understood. Here, we identify SEC16B, a scaffold protein localized at the ER exit sites (ERES), as a key regulator of hepatic lipid secretion and storage. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in SEC16B to be highly related to plasma lipid levels in humans. In mice, hepatic Sec16b deficiency reduces serum lipid levels by impairing MTP-independent VLDL lipidation and disrupting COPII-mediated intracellular trafficking. Additionally, SEC16B partially localizes at ER-lipid droplet contact sites, where it promotes lipid droplet expansion by facilitating the recruitment of ER proteins to lipid droplets. More importantly, Sec16b deletion significantly lowers serum lipids and decreases atherosclerotic lesion size in Ldlr null mice. Taken together, these findings uncover a novel mechanism coordinating VLDL and lipid droplet metabolism and highlight SEC16B as a promising therapeutic target for atherosclerosis.

Graduation Semester

2025-05

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/129686

Copyright and License Information

Copyright 2025 Wei Lu

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