Faculty Collaboration Database

Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI-Mediated High-Density Lipoprotein Uptake. Arterioscler Thromb Vasc Biol 2021 Nov;41(11):2708-2725

Date

09/24/2021

Pubmed ID

34551590

Pubmed Central ID

PMC8551036

DOI

10.1161/ATVBAHA.121.316615

Scopus ID

2-s2.0-85118592107 (requires institutional sign-in at Scopus site)   6 Citations

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 protein-protein 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.

Author List

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

Authors

Benjamin N. Gantner PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of Wisconsin
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adipocytes
Adipogenesis
Adiposity
Adult
Animals
Atherosclerosis
CHO Cells
Caveolin 1
Cholesterol, HDL
Cricetulus
Diet, High-Fat
Disease Models, Animal
Energy Metabolism
Extracellular Matrix Proteins
Female
Glycoproteins
Humans
Inflammation Mediators
Intracellular Signaling Peptides and Proteins
Male
Membrane Microdomains
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Obesity
Receptors, LDL
Scavenger Receptors, Class B
Subcutaneous Fat