Role of PAI-1 in hepatic steatosis and dyslipidemia

Abstract Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 is a mechanistic contributor to several elements of the syndrome, including obesity, hypertension and insulin resistance. Here we show that PAI-1 is a...

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Autores principales:	Joshua A. Levine, Carlota Oleaga, Mesut Eren, Ansel P. Amaral, Meng Shang, Elizabeth Lux, Sadiya S. Khan, Sanjiv J. Shah, Yasuhiro Omura, Nathalie Pamir, Joshua Hay, Grant Barish, Toshio Miyata, Hagai Tavori, Sergio Fazio, Douglas E. Vaughan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70f544abac804254b08f94ba760c8b5e
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spelling	oai:doaj.org-article:70f544abac804254b08f94ba760c8b5e2021-12-02T14:01:34ZRole of PAI-1 in hepatic steatosis and dyslipidemia10.1038/s41598-020-79948-x2045-2322https://doaj.org/article/70f544abac804254b08f94ba760c8b5e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79948-xhttps://doaj.org/toc/2045-2322Abstract Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 is a mechanistic contributor to several elements of the syndrome, including obesity, hypertension and insulin resistance. Here we show that PAI-1 is also a critical regulator of hepatic lipid metabolism. RNA sequencing revealed that PAI-1 directly regulates the transcriptional expression of numerous genes involved in mammalian lipid homeostasis, including PCSK9 and FGF21. Pharmacologic or genetic reductions in plasma PAI-1 activity ameliorates hyperlipidemia in vivo. These experimental findings are complemented with the observation that genetic deficiency of PAI-1 is associated with reduced plasma PCSK9 levels in humans. Taken together, our findings identify PAI-1 as a novel contributor to mammalian lipid metabolism and provides a fundamental mechanistic insight into the pathogenesis of one of the most pervasive medical problems worldwide.Joshua A. LevineCarlota OleagaMesut ErenAnsel P. AmaralMeng ShangElizabeth LuxSadiya S. KhanSanjiv J. ShahYasuhiro OmuraNathalie PamirJoshua HayGrant BarishToshio MiyataHagai TavoriSergio FazioDouglas E. VaughanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joshua A. Levine Carlota Oleaga Mesut Eren Ansel P. Amaral Meng Shang Elizabeth Lux Sadiya S. Khan Sanjiv J. Shah Yasuhiro Omura Nathalie Pamir Joshua Hay Grant Barish Toshio Miyata Hagai Tavori Sergio Fazio Douglas E. Vaughan Role of PAI-1 in hepatic steatosis and dyslipidemia
description	Abstract Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 is a mechanistic contributor to several elements of the syndrome, including obesity, hypertension and insulin resistance. Here we show that PAI-1 is also a critical regulator of hepatic lipid metabolism. RNA sequencing revealed that PAI-1 directly regulates the transcriptional expression of numerous genes involved in mammalian lipid homeostasis, including PCSK9 and FGF21. Pharmacologic or genetic reductions in plasma PAI-1 activity ameliorates hyperlipidemia in vivo. These experimental findings are complemented with the observation that genetic deficiency of PAI-1 is associated with reduced plasma PCSK9 levels in humans. Taken together, our findings identify PAI-1 as a novel contributor to mammalian lipid metabolism and provides a fundamental mechanistic insight into the pathogenesis of one of the most pervasive medical problems worldwide.
format	article
author	Joshua A. Levine Carlota Oleaga Mesut Eren Ansel P. Amaral Meng Shang Elizabeth Lux Sadiya S. Khan Sanjiv J. Shah Yasuhiro Omura Nathalie Pamir Joshua Hay Grant Barish Toshio Miyata Hagai Tavori Sergio Fazio Douglas E. Vaughan
author_facet	Joshua A. Levine Carlota Oleaga Mesut Eren Ansel P. Amaral Meng Shang Elizabeth Lux Sadiya S. Khan Sanjiv J. Shah Yasuhiro Omura Nathalie Pamir Joshua Hay Grant Barish Toshio Miyata Hagai Tavori Sergio Fazio Douglas E. Vaughan
author_sort	Joshua A. Levine
title	Role of PAI-1 in hepatic steatosis and dyslipidemia
title_short	Role of PAI-1 in hepatic steatosis and dyslipidemia
title_full	Role of PAI-1 in hepatic steatosis and dyslipidemia
title_fullStr	Role of PAI-1 in hepatic steatosis and dyslipidemia
title_full_unstemmed	Role of PAI-1 in hepatic steatosis and dyslipidemia
title_sort	role of pai-1 in hepatic steatosis and dyslipidemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/70f544abac804254b08f94ba760c8b5e
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Role of PAI-1 in hepatic steatosis and dyslipidemia

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