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Cited by 132Lipid metabolism and biosynthesisLipid metabolism and disordersCholesterol and Lipid Metabolism

Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis

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Sołtysik, Kamil, Ohsaki, Yuki, Tatematsu, Tsuyako, Cheng, Jinglei, Fujimoto, Toyoshi·2019·Nature Communications
DOI 10.1038/s41467-019-08411-xPMC PMC6349838
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Abstract

The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here we show that nuclear LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs, a precursor to very low-density lipoproprotein (VLDL) generated in the ER lumen by microsomal triglyceride transfer protein. ApoB-free lumenal LDs accumulate under ER stress, grow within the lumen of the type I nucleoplasmic reticulum, and turn into nucleoplasmic LDs by disintegration of the surrounding inner nuclear membrane. Oleic acid with or without tunicamycin significantly increases the formation of nucleoplasmic LDs, to which CTP:phosphocholine cytidylyltransferase α (CCTα) is recruited, resulting in activation of phosphatidylcholine (PC) synthesis. Perilipin-3 competes with CCTα in binding to nucleoplasmic LDs, and thus, knockdown and overexpression of perilipin-3 increases and decreases PC synthesis, respectively. The results indicate that nucleoplasmic LDs in hepatocytes constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.

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  • APOE and APOCIII were identified on nuclear lipid droplets in HepG2 cells, and APOAV has been reported on the surface of cytoplasmic lipid droplets in adipocytes.

    “APOE and APOCIII were identified on nuclear LDs in HepG2 cells, and APOAV has previously been reported on the surface of cytoplasmic LDs in adipocytes (Shu et al., 2010; Gao et al., 2012; Sołtysik et al., 2019).”

    From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Sołtysik et al., 2019

    The Results section (‘NR-lumenal LDs are converted to nucleoplasmic LDs,’ Fig. 3a) reports ApoE and ApoCIII on some nuclear lipid droplets, but its figure caption identifies the cells as Huh7, not HepG2. The APOAV finding in adipocytes is not reported in this paper and appears to be covered by the other citations in the sentence. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • APOV and APOCIII have been shown to go to lipid droplets.

    “APOV and APOCIII have been shown to go to LDs (Shu et al., 2010; Gao et al., 2012; Sołtysik et al., 2019).”

    From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Sołtysik et al., 2019

    The Results section (‘NR-lumenal LDs are converted to nucleoplasmic LDs’; page unavailable) reports that ApoCIII binds lumenal lipid droplets and was occasionally found in nucleoplasmic lipid droplets. It reports this for ApoE, not APOV, so the APOV part of the claim is not supported by our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Sołtysik, K., Ohsaki, Y., Tatematsu, T., Cheng, J., & Fujimoto, T.
Affiliations
Nagoya University (JP)
Corresponding author
  • Ohsaki, Yuki
  • Fujimoto, Toyoshi
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-01-28
Volume
10
Issue
1
Pages
473-473
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-08411-x
PMC
PMC6349838
OpenAlex
W2911407401
Cited by
132
References
1
Citations by year
2026: 10 · 2025: 12 · 2024: 21 · 2023: 22 · 2022: 16 · 2021: 23 · 2020: 23 · 2019: 5
FWCI
6.89
Type
journal article
Language
en
Update notices
correction (2019-03-12)
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (JP16H06280, 15H05902)
  • Japan Society for the Promotion of Science (18H04023, 16H06280, 15H05902, 18K06829, 15H05897)
  • National Institute for Basic Biology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
nuclear lipid droplets, phosphatidylcholine synthesis, VLDL, microsomal triglyceride transfer protein, endoplasmic reticulum stress, inner nuclear membrane, oleic acid, tunicamycin, PLIN3, hepatocytes
MeSH terms
Perilipin-3, A549 Cells, Animals, Cell Nucleus, HeLa Cells, Humans, Lipoproteins, Phosphatidylcholines, Protein Precursors, Oleic Acid, Choline-Phosphate Cytidylyltransferase, Hepatocytes, Cell Line, Tumor, Rats, HEK293 Cells, Lipid Droplets

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