Abstract

Background: Flavonoids are documented for their potential anti-adipogenic, anti-inflammatory and anti-diabetic effects. Quercetin, one of the most abundant flavonoids in edible plants, was investigated for these effects in a diabetic mouse model (db/db, leptin receptor mutation) exerting early relevant clinical signs of non-insulin dependent diabetes mellitus, such as hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypoadiponectinemia and obesity. Materials & Methods: Female db/db mice (n = 24) were fed a flavonoid-poor maintenance diet without (C) or with the addition of quercetin (0.3 g/kg diet, Q) or rosiglitazone (4 mg/kg diet, TZD). Food and water were freely available during the 4 week feeding period. Thereafter, blood samples (fasted) were analyzed for glucose, insulin, triacylglycerols, non-esterified fatty acids, cholesterol, adiponectin and soluble intercellular adhesion molecule-1 (sICAM-1). Adiponectin mRNA levels were measured in adipose tissue. Furthermore, sICAM-1 release was investigated using tumor necrosis factor alpha stimulated EAhy926 cells. Results: Only TZD treatment reduced fasted plasma glucose, triacylglycerols and cholesterol and increased plasma adiponectin concentrations compared to groups C and Q. Adiponectin mRNA levels after quercetin treatment were not different from TZD-treatment or controls. Only quercetin treatment reduced sICAM-1 release in vitro and in vivo. Conclusions: Quercetin effectively reduced sICAM-1 release in the progressive diabetic state, revealing its anti-inflammatory potential in vivo.

Highlights

  • Obesity is associated with endocrine dysfunction of adipose tissue resulting in elevated secretion of pro-inflammatory cytokines [1], oxidative stress [2], and hypoadiponectinemia [3] contributing to the pathogenesis of insulin resistance [4]

  • Four weeks of oral quercetin treatment of female db/db mice reduced plasma soluble intercellular adhesion molecule-1 (sICAM-1) concentrations compared to controls (Table 3). sICAM-1 concentrations tended (P < 0.058) to be lower in the quercetin-treated group compared to in the TZD-treated group (Table 3)

  • In contrast to TZD treatment, quercetin treatment did not result in reduced fasting plasma glucose, TG or cholesterol levels compared to controls (Table 3)

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Summary

Introduction

Obesity is associated with endocrine dysfunction of adipose tissue resulting in elevated secretion of pro-inflammatory cytokines [1], oxidative stress [2], and hypoadiponectinemia [3] contributing to the pathogenesis of insulin resistance [4]. Cytokines, such as tumor necrosis factor alpha (TNF-α), induce the expression and release of adhesion molecules (ICAM-1) in different cell types [5]. Conclusions: Quercetin effectively reduced sICAM-1 release in the progressive diabetic state, revealing its anti-inflammatory potential in vivo

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