2. Academic Validation
  3. Cytoskeleton regulates lipid droplet fusion and lipid storage by controlling lipid droplet movement

Cytoskeleton regulates lipid droplet fusion and lipid storage by controlling lipid droplet movement

  • Biochim Biophys Acta Mol Cell Biol Lipids. 2025 May;1870(4):159610. doi: 10.1016/j.bbalip.2025.159610.
Yan Liang 1,  Zanzan Zhu 1,  Yiming Lu 1,  Chengxin Ma 1,  Jiacheng Li 1,  Kuan Yu 1,  Jin Wu 1,  Xinmeng Che 1,  Xu Liu 1,  Xiaoxiao Huang 1,  Peng Li 2,  Feng-Jung Chen 3
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China.
  • 2 Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China; State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Shanghai Qi Zhi Institute, Shanghai 200030, China.
  • 3 Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China; Shanghai Qi Zhi Institute, Shanghai 200030, China. Electronic address: derrick_chen@fudan.edu.cn.
PMID: 40189192 DOI: 10.1016/j.bbalip.2025.159610
Abstract

Lipid droplets (LDs) are highly dynamic organelles that maintain cellular lipid homeostasis through size and number control. In adipose tissue, CIDEC plays a crucial role in LD fusion and lipid homeostasis. However, the regulatory factors and mechanisms of LD fusion remain largely unknown. Here, we established a high-throughput LD phenotypic screen on a compound library consisting of 2010 small molecules, and identified 11 Cytoskeleton inhibitors that negatively regulate LD size. Using specific inhibitors against each of the three types of Cytoskeleton, our data showed that the disruption of microtubules and microfilaments but not intermediate filaments limits CIDEC-mediated LD fusion and growth by reducing LD movement and LD-LD contact. The collective effect of microtubule inhibitors results in a small LD phenotype which favors lipolysis upon activation of cAMP-PKA pathway in adipocytes. Our findings demonstrate that Cytoskeleton is involved in the process of LD fusion and growth, indicating their role in lipid storage metabolism. One-Sentence Summary: Cytoskeleton regulates lipid droplet fusion and lipid storage.

Keywords

CIDEC; Cytoskeleton; Lipid droplet contact; Lipid droplet movement; Microtubule.

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