Nutr Res Pract.  2023 Jun;17(3):438-450. 10.4162/nrp.2023.17.3.438.

Quercetin inhibits body weight gain and adipogenesis via matrix metalloproteinases in mice fed a highfat diet

• Song S
• Ha AW
• Kim W

• KMID: 2542841
• DOI: http://doi.org/10.4162/nrp.2023.17.3.438

Abstract

BACKGROUND/OBJECTIVES
Limited studies reported that quercetin inhibited adipogenesis and neovascularization by inhibiting matrix metalloproteinases (MMPs) activity, but such mechanisms have not been elucidated in animal experiments. In this study, we investigated the inhibitory effects of quercetin on weight gain and adipose tissue growth through the regulation of mRNA expressions of adipogenic transcription factors and MMPs in mice fed a high-fat diet (HFD).
MATERIALS/METHODS
Five-wk-old C57BL/6J mice were fed a normal diet (ND), HFD, HFD containing 0.05% of quercetin (HFQ0.05), or HFD containing 0.15% of quercetin (HFQ0.15) for 16 wks. Glycerol-3-phosphate dehydrogenase (GPDH) activity was measured using a commercial kit. The mRNA expressions of transcription factors related to adipocyte differentiation were determined by real-time polymerase chain reaction (PCR). The mRNA expressions of MMPs and concentrations of MMPs were measured by real-time PCR and enzyme-linked immunosorbent assay kit, respectively.
RESULTS
Quercetin intake reduced body weight gain and epididymal adipose tissue weights (P < 0.05). GPDH activity was higher in the HFD group than in the ND group but lower in the quercetin groups (P < 0.05). The mRNA expressions of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, peroxisome proliferator-activated receptor γ, and fatty acid-binding protein 4 were lower in the quercetin groups than in the HFD group (P < 0.05). Similarly, the mRNA expression and concentrations of MMP-2 and MMP-9 were significantly lower in the quercetin groups than in the HFD group (P < 0.05).
CONCLUSION
The study confirms that quercetin suppresses body weight gain and adipogenesis by inhibiting transcription factors related to adipocyte differentiation and MMPs (MMP-2 and MMP-9), in mice fed a HFD.

Keyword

Quercetin; adipogenesis; angiogenesis; matrix metalloproteinase; obesity

Figure

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  Fig. 1 Body weight changes in the experimental groups.Lines represent mean weights ± SEs of the experimental groups. Five-wk-old C57BL/6J mice (Daehan Biolink) were randomly allocated to 4 experimental groups: normal fat diet (ND); high fat diet (HFD); high fat diet + quercetin 0.05% (HFQ0.05); and high fat diet + quercetin 0.15% (HFQ0.15).NS, no significant intergroup difference.Different symbols above lines for each wk indicate significant intergroup differences at P < 0.05 as determined by Duncans multiple range test.

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  Fig. 2 Effect of 16 weeks of quercetin administration on GPDH activity in adipose tissues.Bars represent means ± SEs of the experimental groups. Five-wk-old C57BL/6J mice (Daehan Biolink) were randomly allocated to 4 experimental groups:normal fat diet (ND); high fat diet (HFD); high fat diet + quercetin 0.05% (HFQ0.05); and high fat diet + quercetin 0.15% (HFQ0.15).GPDH, glycerol-3-phosphate dehydrogenase.Different letters above bars indicate significant intergroup differences at P < 0.05 as determined by Duncans multiple range test.

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  Fig. 3 Effects of 16 weeks of quercetin administration on the mRNA expressions of transcription factors related to adipocyte differentiation in the liver.Total RNA was isolated using TRI-Reagent, and cDNA was synthesized using SuperScript II reverse transcriptase from total RNA. Real-time PCR with SYBR Green was performed using standard procedures to assess the mRNA expressions in liver samples obtained from each group. β-Actin levels were used to ensure equal loadings. Applied Biosystems StepOne software v2.1 was used. Bars represent means ± SEs of the experimental groups. Five-wk-old C57BL/6J mice (Daehan Biolink) were randomly allocated to 4 experimental groups: normal fat diet (ND); high fat diet (HFD); high fat diet + quercetin 0.05% (HFQ0.05); and high fat diet + quercetin 0.15% (HFQ0.15).PCR, polymerase chain reaction; C/EBPβ, CCAT/enhancer-binding protein β; C/EBPα, CCAT/enhancer-binding protein α; PPARγ, peroxisome proliferator activated receptor γ; FABP4, fatty acid binding protein 4.Different letters above bars indicate significant intergroup differences (P < 0.05 as determined by Duncans multiple range test).

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  Fig. 4 Effects of 16 weeks of quercetin administration on mRNA expression, concentrations of MMP-2 in adipose tissues.To measure the mRNA expression of MMP-2, total RNA was isolated using TRI-Reagent, and cDNA was synthesized using total RNA and SuperScript II reverse transcriptase. Real-time PCR with SYBR Green was performed using standard procedures to assess mRNA expressions in epididymal fat pad samples. (A) β-Actin levels were used to ensure equal loadings. Applied Biosystems StepOne software v2.1 was used. (B) MMP-2 protein levels were measured using the MMP-2 ELISA kit (MBS722437, MyBioSouce. (C) MMP-2 activity was measured using the MMP-2 Biotrack activity assay system kit (RPN 2631; GE Healthcare. Bars represent means ± SEs of the experimental groups. Five-wk-old C57BL/6J mice (Daehan Biolink) were randomly allocated to 4 experimental groups: normal fat diet (ND); high fat diet (HFD); high fat diet + quercetin 0.05% (HFQ0.05); and high fat diet + quercetin 0.15% (HFQ0.15).MMP, matrix metalloproteinase.Different letters above bars indicate significant intergroup differences (P < 0.05 as determined by Duncans multiple range test).

• 

  Fig. 5 Effects of 16 weeks of quercetin administration on the mRNA expression, concentrations of MMP-9 in adipose tissues.To measure the mRNA expression of MMP-9, total RNA was isolated using TRI-Reagent, and cDNA was synthesized using total RNA with SuperScript II reverse transcriptase. Real-time PCR with SYBR Green was performed using standard procedures to determine mRNA expressions in epididymal fat pad samples. (A) β-Actin levels were used to ensure equal loadings. Applied Biosystems StepOne software v2.1 was used. (B) MMP-9 levels were measured using the MMP-9 ELISA kit (MBS720876, MyBioSource, and (C) MMP-9 activities were measured using an MMP-9 activity assay kit (QuickZyme BioScience). Bars represent means ± SEs of the experimental groups. Five-wk-old C57BL/6J mice (Daehan Biolink) were randomly allocated to 4 experimental groups: normal fat diet (ND); high fat diet (HFD); high fat diet + quercetin 0.05% (HFQ0.05); and high fat diet + quercetin 0.15% (HFQ0.15).MMP, matrix metalloproteinase; PCR, polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay.Different letters above bars indicate significant intergroup differences at P < 0.05 as determined by Duncans multiple range tests.

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