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

doi:10.1016/j.cmet.2018.03.017

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

Applied Medicine

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	1055-1066.e3
Number of pages	12
Journal	Cell Metabolism
Volume	27
Issue number	5
Early online date	1 May 2018
DOIs	https://doi.org/10.1016/j.cmet.2018.03.017
Publication status	Published - 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.

Keywords

chylomicrons
electron microscopy
fatty acids
lipoprotein lipase
NanoSIMS
triglycerides

Access to Document

10.1016/j.cmet.2018.03.017Licence: Unspecified

Cite this

He, C., Weston, T. A., Jung, R. S., Heizer, P., Larsson, M., Hu, X., Allan, C. M., Tontonoz, P., Reue, K., Beigneux, A. P., Ploug, M., Holme, A., Kilburn, M., Guagliardo, P., Ford, D. A., Fong, L. G., Young, S. G., & Jiang, H. (2018). NanoSIMS Analysis of Intravascular Lipolysis and Lipid Movement across Capillaries and into Cardiomyocytes. Cell Metabolism, 27(5), 1055-1066.e3. https://doi.org/10.1016/j.cmet.2018.03.017

He, C, Weston, TA, Jung, RS, Heizer, P, Larsson, M, Hu, X, Allan, CM, Tontonoz, P, Reue, K, Beigneux, AP, Ploug, M, Holme, A, Kilburn, M, Guagliardo, P, Ford, DA, Fong, LG, Young, SG & Jiang, H 2018, 'NanoSIMS Analysis of Intravascular Lipolysis and Lipid Movement across Capillaries and into Cardiomyocytes', Cell Metabolism, vol. 27, no. 5, pp. 1055-1066.e3. https://doi.org/10.1016/j.cmet.2018.03.017

@article{aa477ec8c82d438aacd7361002ac5fbf,

title = "NanoSIMS Analysis of Intravascular Lipolysis and Lipid Movement across Capillaries and into Cardiomyocytes",

abstract = " 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. ",

keywords = "chylomicrons, electron microscopy, fatty acids, lipoprotein lipase, NanoSIMS, triglycerides",

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

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.",

year = "2018",

month = may,

day = "1",

doi = "10.1016/j.cmet.2018.03.017",

language = "English",

volume = "27",

pages = "1055--1066.e3",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - NanoSIMS Analysis of Intravascular Lipolysis and Lipid Movement across Capillaries and into Cardiomyocytes

AU - He, Cuiwen

AU - Weston, Thomas A.

AU - Jung, Rachel S.

AU - Heizer, Patrick

AU - Larsson, Mikael

AU - Hu, Xuchen

AU - Allan, Christopher M.

AU - Tontonoz, Peter

AU - Reue, Karen

AU - Beigneux, Anne P.

AU - Ploug, Michael

AU - Holme, Andrea

AU - Kilburn, Matthew

AU - Guagliardo, Paul

AU - Ford, David A.

AU - Fong, Loren G.

AU - Young, Stephen G.

AU - Jiang, Haibo

N1 - 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.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - chylomicrons

KW - electron microscopy

KW - fatty acids

KW - lipoprotein lipase

KW - NanoSIMS

KW - triglycerides

UR - http://www.scopus.com/inward/record.url?scp=85045547686&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2018.03.017

DO - 10.1016/j.cmet.2018.03.017

M3 - Article

C2 - 29719224

AN - SCOPUS:85045547686

SN - 1550-4131

VL - 27

SP - 1055-1066.e3

JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this