Abstract

Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes’ gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis-involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications.

Highlights

  • Obesity confers a high risk of developing numerous metabolic and cardiovascular complications.In the context of extensively growing or prevailing adipose tissue, biochemical and cellular changes take place in adipocytes, in the presence of reduced oxygen supply [1]

  • In the present study we focused on the expression of genes which are known or suspected to be impacted by a hypoxic environment in adipose tissue

  • 6-phosophofructokinase (PFKP), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4), complement factor D (CFD, known as adipsin), fibronectin type III domain-containing 5 (FNDC5, which encodes the precursor of irisin), and interleukin-1β (IL1B)

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Summary

Introduction

Obesity confers a high risk of developing numerous metabolic and cardiovascular complications. In the context of extensively growing or prevailing adipose tissue, biochemical and cellular changes take place in adipocytes, in the presence of reduced oxygen supply [1]. Hypoxia is a major starting point of the inflammatory process in adipose tissue and modulates adipocyte metabolism [2,3,4,5]. There is evidence that this dysregulation of metabolism in adipose tissue under hypoxia promotes insulin resistance and dyslipidemia and initiates the development of diabetes and cardiovascular disease [2,8]. There is growing interest worldwide in plant compounds with respect to their potential to combat obesity and subsequent diseases. Among the more than 4000 flavonoids [9]

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