Nutr Res Pract.  2024 Dec;18(6):806-817. 10.4162/nrp.2024.18.6.806.

Effects of quercetin nanoemulsion on SIRT1 activation and mitochondrial biogenesis in the skeletal muscle of high-fat diet-fed mice

• Lee MS
• Doo M
• Kim Y

• KMID: 2562368
• DOI: http://doi.org/10.4162/nrp.2024.18.6.806

Abstract

BACKGROUND/OBJECTIVES
Quercetin (QT) is a plant flavonoid that offers health benefits owing to its various bioactive properties; however, as a hydrophobic substance, it has considerably low bioavailability. We previously demonstrated that QT nanoemulsion (QT+NE) formulated via oil-in-water nanoemulsification exhibited more effective cholesterollowering activity than ordinary QT in high cholesterol-fed rats. In this study, we investigated the effects of QT+NE on the regulation of skeletal muscle mitochondrial function in high-fat diet (HD)-fed mice.
MATERIALS/METHODS
C57BL/6J mice were fed a normal chow diet (ND), HD (45% of calories from fat), or HD with 0.05% QT+NE or QT for 11 weeks. We analyzed sirtuin 1 (SIRT1) activation, mitochondrial changes, and the expression of genes involved in mitochondrial biogenesis in skeletal muscle.
RESULTS
Body weight and body weight gain decreased in the QT+NE group compared with that in the HD group (P < 0.05), but not in the QT group. Epididymal adipose tissue weight decreased in both the QT and QT+NE groups (P < 0.05). Plasma lipid levels also improved in both the QT and QT+NE groups (P < 0.05). QT+NE intake upregulated the messenger RNA levels of SIRT1, peroxisome proliferator-activated receptor-γ coactivator 1-α, nuclear respiratory factor 1, and mitochondrial transcription factor A in skeletal muscle compared with HD intake alone (P < 0.05), whereas QT did not. In particular, SIRT1 activity was significantly increased in the QT+NE group compared with that in the QT group (P < 0.05). HD intake reduced mitochondrial DNA content compared with ND intake; nevertheless, QT+NE intake retained it (P < 0.05).
CONCLUSION
Collectively, our findings suggest that QT+NE may be beneficial in enhancing mitochondrial biogenesis in skeletal muscle of HD-fed mice, which may be associated with SIRT1 activation.

Keyword

Quercetin; sirtuin 1; mitochondrial biogenesis; skeletal muscle; obesity

Figure

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  Fig. 1 Effects of QT+NE and QT on body weight and epididymal fat accumulation. (A) Body weight gain. (B) EAT weight. (C) EAT H&E staining (scale bar = 50 μm; magnification of 400×). (D) EAT adipocyte size (area per adipocyte, μm2). Values are expressed as the mean ± standard error of the mean (n = 6).ND, normal chow diet; HD, high-fat diet; QT, quercetin; QT+NE, quercetin nanoemulsion; EAT, epididymal adipose tissue; H&E, hematoxylin and eosin.a,bDifferent letters indicate significant differences among the 3 groups (HD, QT+NE, and QT groups) at P < 0.05. Significant differences between the ND and HD groups are indicated: **P < 0.01.

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  Fig. 2 Effects of QT+NE and QT on SIRT1 regulation in skeletal muscle. SIRT1 mRNA expression (A) and activity (B). Values are expressed as the mean ± standard error of the mean (n = 6).ND, normal chow diet; HD, high-fat diet; QT, quercetin; QT+NE, quercetin nanoemulsion; SIRT1, sirtuin 1; mRNA, messenger RNA.a,bDifferent letters indicate significant differences among the 3 groups (HD, QT+NE, and QT groups) at P < 0.05. Significant differences between the ND and HD groups are indicated: **P < 0.01.

• 

  Fig. 3 Effects of QT+NE and QT on mitochondrial biogenesis in skeletal muscle. (A) mRNA expression levels of Pgc-1α, Nrf1, and Tfam. (B) mtDNA content. (C) TEM imaging (scale bar = 2 μm; magnification of 20,000×). Red arrows indicate mitochondria. Values are expressed as the mean ± standard error of the mean (n = 6).ND, normal chow diet; HD, high-fat diet; QT, quercetin; QT+NE, quercetin nanoemulsion; mRNA, messenger RNA; Pgc-1α, peroxisome proliferator-activated receptor-γ coactivator 1-α; Nrf1, nuclear respiratory factor 1; Tfam, mitochondrial transcription factor A; TEM, transmission electron microscope; mtDNA, mitochondrial DNA.a,bDifferent letters indicate significant differences among the 3 groups (HD, QT+NE, and QT groups) at P < 0.05. Significant differences between the ND and HD groups are indicated: **P < 0.01.

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  Fig. 4 Mechanistic schematic showing the potential effects of QT+NE on SIRT1 activation and mitochondrial biogenesis in skeletal muscle.QT+NE, quercetin nanoemulsion; SIRT1, sirtuin 1; Pgc-1α, peroxisome proliferator-activated receptor-γ coactivator 1-α; Nrf1, nuclear respiratory factor 1; Tfam, mitochondrial transcription factor A; mtDNA, mitochondrial DNA.

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