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. 2018 Jun 30;27(2):102-109.
doi: 10.7570/jomes.2018.27.2.102.

Quercetin Upregulates Uncoupling Protein 1 in White/Brown Adipose Tissues through Sympathetic Stimulation

Hyunjung Choi  1 , Chu-Sook Kim  1 , Rina Yu  1
Affiliations

Quercetin Upregulates Uncoupling Protein 1 in White/Brown Adipose Tissues through Sympathetic Stimulation

Hyunjung Choi et al. J Obes Metab Syndr. .

Abstract

Background: Uncoupling protein 1 (UCP1) plays an important role in increasing energy expenditure; thus, it is being considered as a new target for preventing obesity and metabolic complications. In this study, we investigated the effect of quercetin, a naturally occurring flavonoid, on UCP1 expression in white/brown adipose tissues (WAT/BAT).

Methods: Mice were fed a high-fat diet (HFD) supplemented with or without dietary quercetin for 9 weeks, and 3T3-L1 adipocytes were treated with quercetin. Expression of UCP1 and other thermogenic genes/proteins was measured by real-time polymerase chain reaction and/or Western blotting.

Results: Dietary quercetin supplementation increased the level of UCP1 in both WAT and/or BAT of HFD-fed obese mice, which was accompanied by upregulated mRNA levels of thermogenesis-related genes. Quercetin supplementation enhanced the plasma norepinephrine level and tended to upregulate β-adrenergic receptor mRNA level in the WAT of HFD-fed obese mice, accompanied by AMP-activated protein kinase (AMPK) activation. Moreover, quercetin enhanced UCP1 expression in 3T3-L1 adipocytes, and this was blunted by treatment with a peroxisome proliferator-activated receptor gamma (PPARγ) antagonist.

Conclusion: These findings suggest that quercetin upregulates UCP1, implying increased WAT browning and BAT activity, via activation of the AMPK/PPARγ pathway through sympathetic stimulation. Quercetin may be useful for preventing obesity and metabolic complications.

Keywords: Adipose tissue; Obesity; Quercetin; Uncoupling protein 1.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Dietary quercetin enhances expression of uncoupling protein 1 (UCP1) and thermogenic genes in white adipose tissue (WAT). C57BL/6 mice were fed a high-fat diet (HFD) without or with 0.05% quercetin (HFD or HFD+Que) for 9 weeks. (A) Sections obtained from WAT (inguinal adipose tissue) were stained with H&E and an anti-UCP1 antibody. Original magnification, ×200. The arrows indicate increased UCP1 staining. (B) A representative Western blot showing protein expression levels of UCP1, peroxisome proliferator-activated receptor gamma (PPARγ), and PPARγ coactivator 1-alpha (PGC1α) in inguinal adipose tissue. (C) Expression of thermogenic markers and mitochondrial biogenesis markers were measured by real-time polymerase chain reaction. Results are mean±standard error of the mean (SEM; n=6 mice per group). *P<0.05; †P<0.01; ‡P<0.001 compared with control obese mice. (D) 3T3-L1 adipocytes were treated with or without quercetin and/or GW9662 (PPARγ antagonist). Results are mean±SEM of three independent experiments. *P<0.05 compared with control.
Figure 2
Figure 2
Dietary quercetin increases levels of norepinephrine in plasma and β3AR mRNA in white adipose tissue (WAT). C57BL/6 mice were fed a high-fat diet (HFD) without or with 0.05% quercetin (HFD or HFD+Que) for 9 weeks. (A) Norepinephrine levels in plasma were measured by enzyme-linked immunosorbent assay. (B) Expression of β3AR mRNA in inguinal WAT. Results are mean±standard error of the mean (n=5–6 mice per group). A representative Western blot showing protein expression levels of (C) cyclic AMP-dependent protein kinase (PKA) and (D) pAMPK/AMPK in inguinal WAT. *P<0.05; †P<0.01 compared with obese control mice. AMPK, AMP-activated protein kinase; pAMPK, phosphorylated AMPK.
Figure 3
Figure 3
Dietary quercetin increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). C57BL/6 mice were fed a high-fat diet (HFD) without or with 0.05% quercetin (HFD or HFD+Que) for 9 weeks. (A) Sections obtained from BAT were stained with H&E and an anti-UCP1 antibody. Original magnification, ×200. The arrows indicate increased UCP1 staining. (B) A representative Western blot showing protein expression of UCP1 in BAT. Results are mean±standard error of the mean (n=6 mice per group). *P<0.05 compared with control.
Figure 4
Figure 4
Schematic presentation of quercetin action on uncoupling protein 1 (UCP1) induction. Quercetin enhances UCP1 expression through AMPK/PPARγ activation and sympathetic stimulation, promoting white adipose tissue browning and brown adipose tissue activation. β3AR, β3-adrenergic receptor; PPARγ, peroxisome proliferator-activated receptor gamma; PGC1α, PPARγ coactivator 1-alpha; AMPK, AMP-activated protein kinase; PKA, cyclic AMP-dependent protein kinase.
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