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Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI-Mediated High-Density Lipoprotein Uptake.
Xu, Hao; Thomas, Michael J; Kaul, Sushma; Kallinger, Rachel; Ouweneel, Amber B; Maruko, Elisa; Oussaada, Sabrina M; Jongejan, Aldo; Cense, Huib A; Nieuwdorp, Max; Serlie, Mireille J; Goldberg, Ira J; Civelek, Mete; Parks, Brian W; Lusis, Aldons J; Knaack, Darcy; Schill, Rebecca L; May, Sarah C; Reho, John J; Grobe, Justin L; Gantner, Benjamin; Sahoo, Daisy; Sorci-Thomas, Mary G.
Afiliación
  • Xu H; Department of Medicine, Division of Endocrinology and Molecular Medicine (H.X., S.K., A.B.O., E.M., B.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
  • Thomas MJ; Pharmacology & Toxicology (M.J.T., R.K., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
  • Kaul S; Cardiovascular Center (M.J.T., J.L.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
  • Kallinger R; Department of Medicine, Division of Endocrinology and Molecular Medicine (H.X., S.K., A.B.O., E.M., B.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
  • Ouweneel AB; Pharmacology & Toxicology (M.J.T., R.K., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
  • Maruko E; Department of Medicine, Division of Endocrinology and Molecular Medicine (H.X., S.K., A.B.O., E.M., B.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
  • Oussaada SM; Department of Medicine, Division of Endocrinology and Molecular Medicine (H.X., S.K., A.B.O., E.M., B.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
  • Jongejan A; Department of Endocrinology and Metabolism (S.M.O., M.J.S.), Amsterdam University Medical Centers, Academic Medical Center, the Netherlands.
  • Cense HA; Department of Bioinformatics (A.J.), Amsterdam University Medical Centers, Academic Medical Center, the Netherlands.
  • Nieuwdorp M; Department of Surgery, Rode Kruis Ziekenhuis, Beverwijk, the Netherlands (H.A.C.).
  • Serlie MJ; Department of Internal and Vascular Medicine (M.N.), Amsterdam University Medical Centers, Academic Medical Center, the Netherlands.
  • Goldberg IJ; Department of Endocrinology and Metabolism (S.M.O., M.J.S.), Amsterdam University Medical Centers, Academic Medical Center, the Netherlands.
  • Civelek M; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, New York University Langone School of Medicine (I.J.G.).
  • Parks BW; Department of Biomedical Engineering, University of Virginia, Charlottesville (M.C.).
  • Lusis AJ; Department of Nutritional Sciences, University of Wisconsin-Madison (B.W.P).
  • Knaack D; Department of Medicine, Human Genetics, Microbiology, Immunology and Molecular Genetics, University of California Los Angeles (A.J.L.).
  • Schill RL; Department of Biochemistry (D.K., R.L.S., S.C.M., D.S.), Medical College of Wisconsin, Milwaukee.
  • May SC; Department of Biochemistry (D.K., R.L.S., S.C.M., D.S.), Medical College of Wisconsin, Milwaukee.
  • Reho JJ; Now with Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI (R.L.S.).
  • Grobe JL; Department of Biochemistry (D.K., R.L.S., S.C.M., D.S.), Medical College of Wisconsin, Milwaukee.
  • Gantner B; Department of Physiology (J.J.R., J.L.G.), Medical College of Wisconsin, Milwaukee.
  • Sahoo D; Comprehensive Rodent Metabolic Phenotyping Core, Department of Physiology, Medical College of Wisconsin, Milwaukee (J.J.R., J.L.G.).
  • Sorci-Thomas MG; Cardiovascular Center (M.J.T., J.L.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.
Arterioscler Thromb Vasc Biol ; 41(11): 2708-2725, 2021 11.
Article en En | MEDLINE | ID: mdl-34551590
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicoproteínas / Adipocitos / Microdominios de Membrana / Péptidos y Proteínas de Señalización Intracelular / Grasa Subcutánea / Aterosclerosis / Receptores Depuradores de Clase B / HDL-Colesterol / Obesidad Tipo de estudio: Prognostic_studies Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2021 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicoproteínas / Adipocitos / Microdominios de Membrana / Péptidos y Proteínas de Señalización Intracelular / Grasa Subcutánea / Aterosclerosis / Receptores Depuradores de Clase B / HDL-Colesterol / Obesidad Tipo de estudio: Prognostic_studies Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2021 Tipo del documento: Article