Leptin, Resistin, and Proprotein Convertase Subtilisin/Kexin Type 9: The Role of STAT3.

In a condition of dysfunctional visceral fat depots, as in the case of obesity, alterations in adipokine levels may be detrimental for the cardiovascular system. The proinflammatory leptin and resistin adipokines have been described as possible links between obesity and atherosclerosis. The present study was aimed at evaluating whether proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein metabolism, is induced by leptin and resistin through the involvement of the inflammatory pathway of In HepG2 cells, leptin and resistin up-regulated PCSK9 gene and protein expression, as well as the phosphorylation of duanyu18133. Upon silencing, leptin and resistin lost their ability to activate PCSK9. The knockdown of duanyu18133 did not affect the expression of leptin and resistin receptors or that of PCSK9. The analysis of the human PCSK9 promoter region showed that the two adipokines raised PCSK9 promoter activity via the involvement of a sterol regulatory element motif. In healthy males, a positive association between circulating leptin and PCSK9 levels was found only when the body mass index was <25 kg/m². In conclusion, this study identified duanyu18133 as one of the molecular regulators of leptin- and resistin-mediated transcriptional induction of PCSK9. Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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