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Int. J. Mol. Sci. 2019, 20(2), 245; https://doi.org/10.3390/ijms20020245

PCSK9 is Expressed in Human Visceral Adipose Tissue and Regulated by Insulin and Cardiac Natriuretic Peptides

1
Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, 60126 Ancona, Italy
2
Internal Medicine and Geriatrics, “Hypertension Excellence Centre” of the European Society of Hypertension, IRCCS-INRCA, 60127 Ancona, Italy
3
Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, School of Nutrition, University “Politecnica delle Marche”, 60126 Ancona, Italy
*
Author to whom correspondence should be addressed.
Received: 9 November 2018 / Revised: 5 December 2018 / Accepted: 4 January 2019 / Published: 9 January 2019
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Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein receptor (LDLR), contributing to hypercholesterolemia. Adipose tissue plays a role in lipoprotein metabolism, but there are almost no data about PCSK9 and LDLR regulation in human adipocytes. We studied PCSK9 and LDLR regulation by insulin, atrial natriuretic peptide (ANP, a potent lipolytic agonist that antagonizes insulin), and LDL in visceral adipose tissue (VAT) and in human cultured adipocytes. PCSK9 was expressed in VAT and its expression was positively correlated with body mass index (BMI). Both intracellular mature and secreted PCSK9 were abundant in cultured human adipocytes. Insulin induced PCSK9, LDLR, and sterol-regulatory element-binding protein-1c (SREBP-1c) and -2 expression (SREBP-2). ANP reduced insulin-induced PCSK9, especially in the context of a medium simulating hyperglycemia. Human LDL induced both mature and secreted PCSK9 and reduced LDLR. ANP indirectly blocked the LDLR degradation, reducing the positive effect of LDL on PCSK9. In conclusion, PCSK9 is expressed in human adipocytes. When the expression of PCSK9 is induced, LDLR is reduced through the PCSK9-mediated degradation. On the contrary, when the induction of PCSK9 by insulin and LDL is partially blocked by ANP, the LDLR degradation is reduced. This suggests that NPs could be able to control LDLR levels, preventing PCSK9 overexpression. View Full-Text
Keywords: PCSK9; natriuretic peptides; adipose tissue; lipid metabolism; LDL receptor; insulin PCSK9; natriuretic peptides; adipose tissue; lipid metabolism; LDL receptor; insulin
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Bordicchia, M.; Spannella, F.; Ferretti, G.; Bacchetti, T.; Vignini, A.; Di Pentima, C.; Mazzanti, L.; Sarzani, R. PCSK9 is Expressed in Human Visceral Adipose Tissue and Regulated by Insulin and Cardiac Natriuretic Peptides. Int. J. Mol. Sci. 2019, 20, 245.

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