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bioRxiv2026January 11, 2026Journal Article

Interorganelle competition for linoleic acid underlies steatotic liver pathology.

Chuanhai Zhang1, Dengbao Yang1, Hiroyuki Suzuki2, Gonçalo Dias do Vale3,4, Jingxuan Chen5, Amogh Vaidya6, Kamran Melikov7, Alexandra Swisher7, Jingjing Wang8, Mengchen Ye9, Jin Zhou10, Qiyu Zeng8, Meijuan Bai1, Mei-Jung Lin1, Jeon Lee5, Hao Zhu8, Daniel J Siegwart6, Yujin Hoshida2, Jeffrey G McDonald3,4, Xing Zeng1
1Department of Physiology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
2Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
3Center for Human Nutrition, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
4Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
5Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, TX, 75390, USA.
6Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
7Section on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
8Children's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, Children's Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
9Xaira Therapeutics, Brisbane, CA, 94005, USA.
10Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
PubMed PMC DOI PDF

Abstract

Lipid droplets (LDs) are traditionally viewed as protective organelles that sequester potentially cytotoxic lipids. However, whether and how LD biogenesis in pathological contexts actively rewires interorganelle lipid homeostasis to drive organelle dysfunction and disease progression remains unexplored. Here, we identify the adipocyte-enriched protein calsyntenin 3β (CLSTN3B) as a critical promote…

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