The Inhibitory Effect of Quercetin on Adipose Tissue Inflammation in Mice Fed on a High-fat Diet

Chu-Sook Kim; Rina Yu

Article

Korean J Obes 2014; 23(3): 170-178

Published online September 30, 2014

The Inhibitory Effect of Quercetin on Adipose Tissue Inflammation in Mice Fed on a High-fat Diet

Chu-Sook Kim^*, Rina Yu

Author Affiliations

Department of Food Science and Nutrition, University of Ulsan, Ulsan, Korea

Received: March 5, 2014; Reviewed : March 28, 2014; Accepted: June 12, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background: Obesity-induced adipose inflammation contributes to the development of metabolic disorders such as insulin resistance and type 2 diabetes. In this study, we investigated whether quercetin, a naturally occurring phytochemical, can attenuate adipose tissue inflammation in obese mice.
Methods: Male C57BL/6 mice were randomly assigned into either control (RD, N=6), high fat diet (HFD, N=6), or HFD supplemented with 0.05% quercetin (HFD+Que, N=6) groups and treated with their respective diets for 9 weeks. The inflammatory cytokine proteins were measured by ELISA, and macrophage populations were determined by immunohistochemistry. The inflammatory receptors and downstream signaling molecules were measured by qPCR and western blot, respectively.
Results: We show here that in an HFD-fed mice model, quercetin supplementation reduced adipose tissue weight without affecting HFD-induced body weight gain. Quercetin supplementation reduced expression of inflammatory cytokines (TNF-α, MCP-1, MIP-1α) and macrophage accumulation (F4/80) in adipose tissue of an HFD-fed mice. Quercetin also suppressed the expression of inflammatory receptors (CCR2, TLR4, TNFRSF9) and the activation of downstream inflammatory signaling molecules (JNK, NF-κB) in adipose tissue.
Conclusion: These findings indicate that quercetin can reduce adipose inflammatory responses in mice exposed to HFD by inhibiting inflammatory cytokines production, inflammatory receptor expression and their signaling pathway. Quercetin may be useful for preventing HFD-induced adipose tissue inflammation.

Keywords: Quercetin, Inflammatory receptor, Adipose tissue, Inflammation, Obesity

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Fig. 1. Effect of quercetin on adipose inflammatory responses in HFD-fed mice. Levels of inflammatory protein (A) TNF-α, (B) IL-6, (C) MCP-1, and (D) MIP-1α in adipose tissue from mice fed either a regular diet (RD), a high-fat diet (HFD) or a high-fat diet containing 0.05% quercetin (HFD+Que) for 9 weeks. Adipose tissue (200 mg) was homogenized with 400 ?L of 100 mM Tris-HCl and 250 mM sucrose buffer (pH 7.4) supplemented with protease inhibitors. Lipids were removed by centrifugation at 10,000 g for 10 minutes. Levels of cytokine in homogenates were measured by enzyme-linked immunosorbent assay and normalized for protein. Results are means±SEM. ^*P<0.05, ^†P<0.01, ^‡P<0.001 compared with obese mice fed on HFD.

Fig. 2. Effect of quercetin on macrophage infiltration into adipose tissue of HFD-fed mice. (A) Histological analysis of adipose tissue from mice fed either a regular diet (RD), a high-fat diet (HFD) or a high-fat diet containing 0.05% quercetin (HFD+Que) for 9 weeks. Sections obtained from the animals were stained with hematoxylin/eosin or anti-F4/80 (macrophage) antibody. Original magnification, ×200. Expression of (B) F4/80 mRNA and (C) chemokine receptor (CCR1, CCR2, and CCR5) mRNA in adipose tissue from mice fed either a regular diet (RD), a high-fat diet (HFD) or a high-fat diet containing 0.05% quercetin (HFD+Que) for 9 weeks. Results are means±SEM. ^*P<0.05 compared with obese mice fed on HFD.

Fig. 3. Quercetin suppresses expression of inflammatory receptors/ligands and their signaling pathway. Expression of (A) TLR2/TLR4, and (B) TNFRSF9/TNFSF9 (4-1BB/4-1BBL) gene in adipose tissue from mice fed either a regular diet (RD), a high-fat diet (HFD) or a high-fat diet containing 0.05% quercetin (HFD+Que) for 9 weeks. The intensity of the bands was densitometrically measured and normalized to the mRNA levels of 36B4 gene. Results are means±SEM. ^*P<0.05, ^†P<0.01, ^‡P<0.001 compared with obese mice fed on HFD. Expression of (C) phosphorylated-JNK and JNK (D) IκB-α protein in adipose tissue from mice fed either a regular diet (RD), a high-fat diet (HFD) or a high-fat diet containing 0.05% quercetin (HFD+Que) for 9 weeks. The amount of phosphorylated-JNK, JNK and IκB-α was assessed by western blotting with appropriate antibodies.

Fig. 4. Schematic presentation of the effect of quercetin on inflammatory responses in adipose tissue of HFD-fed mice. Quercetin contributes to the reduction of adipose inflammation by inhibiting inflammatory receptor expression, inflammatory signaling molecule, and cytokine production.

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Primers used for real-time PCR

Body weight, adiposity and the metabolic parameters

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