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

29 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Cell Metabolism
Vol/bind	27
Udgave nummer	5
Sider (fra-til)	1055-1066.e3
Antal sider	16
ISSN	1550-4131
DOI	https://doi.org/10.1016/j.cmet.2018.03.017
Status	Udgivet - 1 maj 2018

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10.1016/j.cmet.2018.03.017

http://www.cell.com/article/S1550413118301955/pdf

Citationsformater

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, bind 27, nr. 5, s. 1055-1066.e3. https://doi.org/10.1016/j.cmet.2018.03.017

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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. ",

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",

year = "2018",

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

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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

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.

U2 - 10.1016/j.cmet.2018.03.017

DO - 10.1016/j.cmet.2018.03.017

M3 - Journal article

C2 - 29719224

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

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