Polyunsaturated fatty acids promote the rapid fusion of lipid droplets in Caenorhabditis elegans

Yanli Wang, Chunxia Li, Jingjing Zhang, Xiumei Xu, Lin Fu, Jie Xu, Hong Zhu, Ying Hu, Chengbin Li, Mengjie Wang, Yingjie Wu, Xiaoju Zou, Bin Liang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Lipid droplets (LDs) are intracellular organelles that dynamically regulate lipids and energy homeostasis in the cell. LDs can grow through either local lipid synthesis or LD fusion. However, how lipids involving in LD fusion for LD growth is largely unknown. Here, we show that genetic mutation of acox-3 (acyl-CoA oxidase), maoc-1 (enoyl-CoA hydratase), dhs-28 (3-hydroxylacyl-CoA dehydrogenase), and daf-22 (3-ketoacyl-CoA thiolase), all involved in the peroxisomal β-oxidation pathway in Caenorhabditis elegans, led to rapid fusion of adjacent LDs to form giant LDs (gLDs). Mechanistically, we show that dysfunction of peroxisomal β-oxidation results in the accumulation of long-chain fatty acid-CoA and phosphocholine, which may activate the sterol-binding protein 1/sterol regulatory element–binding protein to promote gLD formation. Furthermore, we found that inactivation of either FAT-2 (delta-12 desaturase) or FAT-3 and FAT-1 (delta-15 desaturase and delta-6 desaturase, respectively) to block the biosynthesis of polyunsaturated fatty acids (PUFAs) with three or more double bonds (n≥3-PUFAs) fully repressed the formation of gLDs; in contrast, dietary supplementation of n≥3-PUFAs or phosphocholine bearing these PUFAs led to recovery of the formation of gLDs in peroxisomal β-oxidation–defective worms lacking PUFA biosynthesis. Thus, we conclude that n≥3-PUFAs, distinct from other well-known lipids and proteins, promote rapid LD fusion leading to LD growth.

Original languageEnglish
Article number102179
JournalJournal of Biological Chemistry
Volume298
Issue number8
DOIs
StatePublished - Aug 2022
Externally publishedYes

Keywords

  • giant LDs
  • lipid droplet fusion
  • phosphatidylcholines
  • polyunsaturated fatty acids

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