NanoSIMS Analysis of Intravascular Lipolysis and Lipid Movement across Capillaries and into Cardiomyocytes

Cuiwen He, Thomas A. Weston, Rachel S. Jung, Patrick Heizer, Mikael Larsson, Xuchen Hu, Christopher M. Allan, Peter Tontonoz, Karen Reue, Anne P. Beigneux, Michael Ploug, Andrea Holme, Matthew Kilburn, Paul Guagliardo, David A. Ford, Loren G. Fong, Stephen G. Young*, Haibo Jiang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)


The processing of triglyceride-rich lipoproteins (TRLs) in capillaries provides lipids for vital tissues, but our understanding of TRL metabolism is limited, in part because TRL processing and lipid movement have never been visualized. To investigate the movement of TRL-derived lipids in the heart, mice were given an injection of [ 2 H]triglyceride-enriched TRLs, and the movement of 2 H-labeled lipids across capillaries and into cardiomyocytes was examined by NanoSIMS. TRL processing and lipid movement in tissues were extremely rapid. Within 30 s, TRL-derived lipids appeared in the subendothelial spaces and in the lipid droplets and mitochondria of cardiomyocytes. Enrichment of 2 H in capillary endothelial cells was not greater than in cardiomyocytes, implying that endothelial cells may not be a control point for lipid movement into cardiomyocytes. Remarkably, a deficiency of the putative fatty acid transport protein CD36, which is expressed highly in capillary endothelial cells, did not impede entry of TRL-derived lipids into cardiomyocytes. He et al. used NanoSIMS to visualize the movement of triglyceride-rich lipoprotein (TRL)-derived lipids in the heart. TRL-derived lipids moved across endothelial cells and into cardiomyocyte mitochondria and lipid droplets within seconds. Also, loss of CD36 did not impede entry of TRL-derived lipids into cardiomyocytes.

Original languageEnglish
Pages (from-to)1055-1066.e3
Number of pages12
JournalCell Metabolism
Issue number5
Early online date1 May 2018
Publication statusPublished - 1 May 2018

Bibliographical note

We are grateful for the NanoSIMS facilities at California Institute of Technology (Pasadena, CA) and the University of Western Australia (Perth). We acknowledge support from the Leducq Foundation Transatlantic Network grant (12CVD04) (to S.G.Y.), the NIH (P01 HL090553, R01 HL087228, and HL125335 to S.G.Y.), and a Ruth L. Kirschstein National Research Service Award, F32 HL132471 (to C.H.). We also acknowledge the Australian Microscopy & Microanalysis Research Facility and the Science and Industry Endowment Fund for supporting the Ion Probe Facility at the Centre for Microscopy, Characterisation and Analysis at the University of Western Australia. We thank Dr. Marianne Cilluffo for help in preparing tissue sections.

Author Contributions
C.H. designed, performed, and analyzed the experiments, and prepared figures and the initial draft of the paper. T.A.W. performed electron microscopy and prepared tissue sections for NanoSIMS. R.S.J. performed the experiments and analyzed NanoSIMS data. P.H. managed the mouse colony and performed mouse experiments. M.L. performed isolated heart studies. X.H. performed NanoSIMS studies. C.M.A. performed immunohistochemistry studies. P.T., K.R., M.P., and A.P.B. advised on experimental design and data analysis. A.H., M.K., and P.G. assisted with NanoSIMS. D.A.F. performed lipidomics studies. L.G.F. and S.G.Y. analyzed the data and prepared the paper. H.J. performed NanoSIMS and BSE imaging, analyzed the data, and assisted with figures and the paper.


  • chylomicrons
  • electron microscopy
  • fatty acids
  • lipoprotein lipase
  • NanoSIMS
  • triglycerides


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