| Title: | Tissue-selective COPII modulator SEC16B aggravates cardiovascular disease by promoting lipid export |
| Journal: | The EMBO Journal |
| Published: | 24 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42032080/ |
| DOI: | https://doi.org/10.1038/s44318-026-00754-8 |
| URL: | https://link.springer.com/content/pdf/10.1038/s44318-026-00754-8.pdf |
Publication 17853
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
The biogenesis and transport of lipoproteins are essential for systemic homeostasis and cardiometabolic health, yet how the secretory pathway acquires specialization to support high-capacity lipoprotein export remains unclear. Here, we report SEC16B as a tissue-selective modulator of the COPII machinery, critical for the efficient secretion of APOB-containing lipoproteins. Integrative bioinformatic analyses identify that SEC16B co-emerges with core genes involved in lipoprotein biogenesis. Functional studies, coupled with AI-driven prediction, reveal that SEC16B acts as a molecular brake to fine-tune COPII condensation for lipoprotein export. Mining of UK biobank data links SEC16B to metabolic traits in humans and suggests HNF4A-dependent regulation of SEC16B expression. Hepatic deletion of SEC16B in mice markedly reduces circulating APOB, triglycerides and cholesterol, while conferring robust protection against atherosclerosis and cardiac dysfunction and maintaining liver health. Collectively, these findings position SEC16B as a specialized modulator of lipoprotein export via the general secretory (SEC) pathway in the liver, suggesting potential therapeutic avenues for combating cardiometabolic diseases.</p>
16 Authors
- Xiao Wang
- Yating Hu
- Lu Liu
- Runze Huang
- Yawei Wang
- Bing Liu
- Yifei Zhao
- Yuangang Zhu
- Jia Lv
- Liang Liu
- Huimin Wang
- Lingzhi Wu
- Xinxuan Xu
- Yaxin Li
- Guanlin Wang
- Xiao-Wei Chen
Enabling scientific discoveries that improve human health