Pcpe2, a novel extracellular matrix protein, regulates adipocyte sr-bi-mediated high-density lipoprotein uptake

Hao Xu; Michael J. Thomas; Sushma Kaul; Rachel Kallinger; Amber B. Ouweneel; Elisa Maruko; Sabrina M. Oussaada; Aldo Jongejan; Huib A. Cense; Max Nieuwdorp; Mireille J. Serlie; Ira J. Goldberg; Mete Civelek; Brian W. Parks; Aldons J. Lusis; Darcy Knaack; Rebecca L. Schill; Sarah C. May; John J. Reho; Justin L. Grobe; Benjamin Gantner; Daisy Sahoo; Mary G. Sorci-Thomas

doi:https://doi.org/10.1161/ATVBAHA.121.316615

Pcpe2, a novel extracellular matrix protein, regulates adipocyte sr-bi-mediated high-density lipoprotein uptake

Hao Xu, Michael J. Thomas, Sushma Kaul, Rachel Kallinger, Amber B. Ouweneel, Elisa Maruko, Sabrina M. Oussaada, Aldo Jongejan, Huib A. Cense, Max Nieuwdorp, Mireille J. Serlie, Ira J. Goldberg, Mete Civelek, Brian W. Parks, Aldons J. Lusis, Darcy Knaack, Rebecca L. Schill, Sarah C. May, John J. Reho, Justin L. GrobeBenjamin Gantner, Daisy Sahoo, Mary G. Sorci-Thomas

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

6 Citations (Scopus)

Abstract

OBJECTIVE: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)-mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. APPROACH AND RESULTS: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular proteinprotein interactions, supporting SR-BI- mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI-mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI- mediated HDL-C uptake is unknown. Differentiated cells from Ldlr-/-/Pcpe2-/- (Pcpe2-/-) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake compared to Ldlr-/- (control) adipose tissue. SR-BI-mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. CONCLUSIONS: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans.

Original language	English
Pages (from-to)	2708-2725
Number of pages	18
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Early online date	2021
DOIs	https://doi.org/10.1161/ATVBAHA.121.316615
Publication status	E-pub ahead of print - 2021

Keywords

Adipose tissue
Cholesterol
Diet
Extracellular matrix
HDL
Lipoprotein
Metabolism
Pcolce2

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https://doi.org/10.1161/ATVBAHA.121.316615

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Xu, H., Thomas, M. J., Kaul, S., Kallinger, R., Ouweneel, A. B., Maruko, E., Oussaada, S. M., Jongejan, A., Cense, H. A., Nieuwdorp, M., Serlie, M. J., Goldberg, I. J., Civelek, M., Parks, B. W., Lusis, A. J., Knaack, D., Schill, R. L., May, S. C., Reho, J. J., ... Sorci-Thomas, M. G. (2021). Pcpe2, a novel extracellular matrix protein, regulates adipocyte sr-bi-mediated high-density lipoprotein uptake. Arteriosclerosis, Thrombosis, and Vascular Biology, 2708-2725. Advance online publication. https://doi.org/10.1161/ATVBAHA.121.316615

@article{36134dff947b4d09afe7865277419249,

title = "Pcpe2, a novel extracellular matrix protein, regulates adipocyte sr-bi-mediated high-density lipoprotein uptake",

abstract = "OBJECTIVE: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)-mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. APPROACH AND RESULTS: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular proteinprotein interactions, supporting SR-BI- mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI-mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI- mediated HDL-C uptake is unknown. Differentiated cells from Ldlr-/-/Pcpe2-/- (Pcpe2-/-) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake compared to Ldlr-/- (control) adipose tissue. SR-BI-mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. CONCLUSIONS: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans.",

keywords = "Adipose tissue, Cholesterol, Diet, Extracellular matrix, HDL, Lipoprotein, Metabolism, Pcolce2",

author = "Hao Xu and Thomas, {Michael J.} and Sushma Kaul and Rachel Kallinger and Ouweneel, {Amber B.} and Elisa Maruko and Oussaada, {Sabrina M.} and Aldo Jongejan and Cense, {Huib A.} and Max Nieuwdorp and Serlie, {Mireille J.} and Goldberg, {Ira J.} and Mete Civelek and Parks, {Brian W.} and Lusis, {Aldons J.} and Darcy Knaack and Schill, {Rebecca L.} and May, {Sarah C.} and Reho, {John J.} and Grobe, {Justin L.} and Benjamin Gantner and Daisy Sahoo and Sorci-Thomas, {Mary G.}",

note = "Funding Information: This work was supported by National Institute of Health Grants HL127649 (M.G. Sorci-Thomas), HL138907 (M.G. Sorci-Thomas, D. Sahoo), HL58012 (D. Sahoo), HL147883 (A.J. Lusis), HL149161 (D. Knaack), HL134850, and HL084207 (J.L. Grobe) American Heart Grant 19TPA34890023 (M.J. Thomas), FP7-305707 (M.J. Serlie and M. Nieuwdorp) and 18EIA33890055 (J.L. Grobe). Publisher Copyright: {\textcopyright} 2021 Lippincott Williams and Wilkins. All rights reserved.",

year = "2021",

doi = "https://doi.org/10.1161/ATVBAHA.121.316615",

language = "English",

pages = "2708--2725",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams & Wilkins",

}

Xu, H, Thomas, MJ, Kaul, S, Kallinger, R, Ouweneel, AB, Maruko, E, Oussaada, SM , Jongejan, A, Cense, HA, Nieuwdorp, M , Serlie, MJ, Goldberg, IJ, Civelek, M, Parks, BW, Lusis, AJ, Knaack, D, Schill, RL, May, SC, Reho, JJ, Grobe, JL, Gantner, B, Sahoo, D & Sorci-Thomas, MG 2021, 'Pcpe2, a novel extracellular matrix protein, regulates adipocyte sr-bi-mediated high-density lipoprotein uptake', Arteriosclerosis, Thrombosis, and Vascular Biology, pp. 2708-2725. https://doi.org/10.1161/ATVBAHA.121.316615

TY - JOUR

T1 - Pcpe2, a novel extracellular matrix protein, regulates adipocyte sr-bi-mediated high-density lipoprotein uptake

AU - Xu, Hao

AU - Thomas, Michael J.

AU - Kaul, Sushma

AU - Kallinger, Rachel

AU - Ouweneel, Amber B.

AU - Maruko, Elisa

AU - Oussaada, Sabrina M.

AU - Jongejan, Aldo

AU - Cense, Huib A.

AU - Nieuwdorp, Max

AU - Serlie, Mireille J.

AU - Goldberg, Ira J.

AU - Civelek, Mete

AU - Parks, Brian W.

AU - Lusis, Aldons J.

AU - Knaack, Darcy

AU - Schill, Rebecca L.

AU - May, Sarah C.

AU - Reho, John J.

AU - Grobe, Justin L.

AU - Gantner, Benjamin

AU - Sahoo, Daisy

AU - Sorci-Thomas, Mary G.

N1 - Funding Information: This work was supported by National Institute of Health Grants HL127649 (M.G. Sorci-Thomas), HL138907 (M.G. Sorci-Thomas, D. Sahoo), HL58012 (D. Sahoo), HL147883 (A.J. Lusis), HL149161 (D. Knaack), HL134850, and HL084207 (J.L. Grobe) American Heart Grant 19TPA34890023 (M.J. Thomas), FP7-305707 (M.J. Serlie and M. Nieuwdorp) and 18EIA33890055 (J.L. Grobe). Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.

PY - 2021

Y1 - 2021

N2 - OBJECTIVE: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)-mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. APPROACH AND RESULTS: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular proteinprotein interactions, supporting SR-BI- mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI-mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI- mediated HDL-C uptake is unknown. Differentiated cells from Ldlr-/-/Pcpe2-/- (Pcpe2-/-) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake compared to Ldlr-/- (control) adipose tissue. SR-BI-mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. CONCLUSIONS: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans.

AB - OBJECTIVE: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)-mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. APPROACH AND RESULTS: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular proteinprotein interactions, supporting SR-BI- mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI-mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI- mediated HDL-C uptake is unknown. Differentiated cells from Ldlr-/-/Pcpe2-/- (Pcpe2-/-) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake compared to Ldlr-/- (control) adipose tissue. SR-BI-mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. CONCLUSIONS: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans.

KW - Adipose tissue

KW - Cholesterol

KW - Diet

KW - Extracellular matrix

KW - HDL

KW - Lipoprotein

KW - Metabolism

KW - Pcolce2

UR - http://www.scopus.com/inward/record.url?scp=85118592107&partnerID=8YFLogxK

U2 - https://doi.org/10.1161/ATVBAHA.121.316615

DO - https://doi.org/10.1161/ATVBAHA.121.316615

M3 - Article

C2 - 34551590

SN - 1079-5642

SP - 2708

EP - 2725

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

ER -

Pcpe2, a novel extracellular matrix protein, regulates adipocyte sr-bi-mediated high-density lipoprotein uptake

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Keywords

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