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CLSTN3B promotes lipid droplet maturation and lipid storage in mouse adipocytes

Author

Listed:
  • Chuanhai Zhang

    (UT Southwestern Medical Center)

  • Mengchen Ye

    (University of California Berkeley)

  • Kamran Melikov

    (National Institutes of Health)

  • Dengbao Yang

    (UT Southwestern Medical Center)

  • Goncalo Dias do Vale

    (UT Southwestern Medical Center)

  • Jeffrey McDonald

    (UT Southwestern Medical Center)

  • Kaitlyn Eckert

    (UT Southwestern Medical Center)

  • Mei-Jung Lin

    (UT Southwestern Medical Center)

  • Xing Zeng

    (UT Southwestern Medical Center)

Abstract

Interorganelle contacts facilitate material exchanges and sustain the structural and functional integrity of organelles. Lipid droplets (LDs) of adipocytes are responsible for energy storage and mobilization responding to body needs. LD biogenesis defects compromise the lipid-storing capacity of adipocytes, resulting in ectopic lipid deposition and metabolic disorders, yet how the uniquely large LDs in adipocytes attain structural and functional maturation is incompletely understood. Here we show that the mammalian adipocyte-specific protein CLSTN3B is crucial for adipocyte LD maturation. CLSTN3B employs an arginine-rich segment to promote extensive contact and hemifusion-like structure formation between the endoplasmic reticulum (ER) and LD, allowing ER-to-LD phospholipid diffusion during LD expansion. CLSTN3B ablation results in reduced LD surface phospholipid density, increased turnover of LD-surface proteins, and impaired LD functions. Our results establish the central role of CLSTN3B in the adipocyte-specific LD maturation pathway that enhances lipid storage and maintenance of metabolic health under caloric overload in mice of both sexes.

Suggested Citation

  • Chuanhai Zhang & Mengchen Ye & Kamran Melikov & Dengbao Yang & Goncalo Dias do Vale & Jeffrey McDonald & Kaitlyn Eckert & Mei-Jung Lin & Xing Zeng, 2024. "CLSTN3B promotes lipid droplet maturation and lipid storage in mouse adipocytes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53750-z
    DOI: 10.1038/s41467-024-53750-z
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    1. Kevin Qian & Marcus J. Tol & Jin Wu & Lauren F. Uchiyama & Xu Xiao & Liujuan Cui & Alexander H. Bedard & Thomas A. Weston & Pradeep S. Rajendran & Laurent Vergnes & Yuta Shimanaka & Yesheng Yin & Yasa, 2023. "CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization," Nature, Nature, vol. 613(7942), pages 160-168, January.
    2. Gonen Golani & Evgenia Leikina & Kamran Melikov & Jarred M. Whitlock & Dilani G. Gamage & Gracia Luoma-Overstreet & Douglas P. Millay & Michael M. Kozlov & Leonid V. Chernomordik, 2021. "Myomerger promotes fusion pore by elastic coupling between proximal membrane leaflets and hemifusion diaphragm," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
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