Role of PAI-1 in hepatic steatosis and dyslipidemia

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

研究成果: Article査読

1 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号430
ジャーナルScientific reports
11
1
DOI
出版ステータスPublished - 2021 12

ASJC Scopus subject areas

  • General

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