Role of PAI-1 in hepatic steatosis and dyslipidemia.

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Levine JA, Oleaga C, Eren M, Amaral AP, Shang M, Lux E, Khan SS, Shah SJ, Omura Y, Pamir N, Hay J, Barish G, Miyata T, Tavori H, Fazio S, Vaughan DE

Role of PAI-1 in hepatic steatosis and dyslipidemia.

Sci Rep. 2021 Jan 11;11(1):430. doi: 10.1038/s41598-020-79948-x.

PubMed ID
33432099 [ View in PubMed
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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.

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