Resveratrol Suppresses PAI-1 Gene Expression in a Human<i>In Vitro</i>Model of Inflamed Adipose Tissue

  • Ivana Zagotta
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstraße 24, 89075 Ulm, Germany
  • Elitsa Y. Dimova
    Department of Biochemistry and Biocenter Oulu, University of Oulu, P.O.B. 3000, 90014 Oulu, Finland
  • Jan-Bernd Funcke
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstraße 24, 89075 Ulm, Germany
  • Martin Wabitsch
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstraße 24, 89075 Ulm, Germany
  • Thomas Kietzmann
    Department of Biochemistry and Biocenter Oulu, University of Oulu, P.O.B. 3000, 90014 Oulu, Finland
  • Pamela Fischer-Posovszky
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstraße 24, 89075 Ulm, Germany

抄録

<jats:p>Increased plasminogen activator inhibitor-1 (PAI-1) levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NF<jats:italic>κ</jats:italic>B pathway. Together, resveratrol can act as NF<jats:italic>κ</jats:italic>B inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.</jats:p>

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