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Quercetin improved hepatic circadian rhythm dysfunction in middle-aged mice fed with vitamin D-deficient diet

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Abstract

We aimed to determine whether quercetin is capable of improving circadian rhythm and metabolism disorder under vitamin D-deficient condition. Middle-aged mice were randomly divided into four groups, namely, control (CON), vitamin D-deficient diet (VDD), quercetin (Q), and quercetin intervention in vitamin D-deficient diet (VDQ), with a total of 12 weeks’ intervention. Mice were sacrificed at zeitgeber time1 (ZT1) and ZT13 time points. At ZT1, circadian locomotor output cycle kaput (CLOCK) protein expression from VDD, Q, and VDQ groups; CRY1 from Q group; and CRY2 from VDD group were significantly lower compared to CON group. The mRNA expression of Sirt1, Bmal1, Clock, Cry1, and Cry2 in VDQ groups, also Bmal1, Clock, and Cry1 from Q group, were significantly decreased compared to CON group. At ZT13, compared to CON group, fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were higher in VDD group; BMAL1 was significantly increased, while CLOCK and CRY1 protein were significantly decreased from VDD group; CLOCK protein from VDQ group was significantly higher compared to CON, VDD, and Q groups, and also, BMAL1 protein expression from VDQ group was elevated compared to CON group. The mRNA expression of Bmal1, Clock, Per2, Cry1, and Cry2 in VDQ groups were significantly increased compared to CON groups. The mRNA expression of Bmal1 from VDQ group was decreased compared to both VDD and Q group. In conclusion, vitamin D-deficient diet resulted in a disordered liver circadian rhythm, and quercetin improved the hepatic circadian desynchronization. Quercetin supplementation might be effective for balancing circadian rhythm under vitamin D-deficient condition.

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Abbreviations

AUC:

The area under the curve

BMAL1:

Brain and Muscle-Arnt-Like 1

CLOCK:

Circadian locomotor output cycles kaput

Cry:

Cryptochrome

EE:

Energy expenditure

FOXO1:

Forkhead box protein O1

HOMA-IR:

Homeostasis model assessment-insulin resistance

ICR:

The Institute of Cancer Research

NAFLD:

Non-alcoholic fatty liver disease

Per:

Period

RER:

Respiratory exchange ratio

SCN:

Suprachiasmatic nucleus

SIRT1:

Silent information regulator 2-related enzyme 1

VDR:

Vitamin D receptor

ZT:

Zeitgeber time

25(OH)D:

25-Hydroxyvitamin D

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Funding

This study was supported by the National Natural Science Foundation of China (Grant NOs. 81872609 and 82073535), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the University Science Research Project of Jiangsu Province (21KJB310021).

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Author notes

  1. Rui Li and Guiping Wang make equal contributions to this study.

Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren’ai Road, Suzhou, 215123, China

    Rui Li, Ruitong Liu, Lan Luo, Ying Zhang & Zhongxiao Wan

  2. Laboratory Animal Center, Medical College of Soochow University, 199 Ren’ai Road, Suzhou, China

    Guiping Wang

  3. Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, No. 568, Zhongxing North Road, Shaoxing, Zhejiang, 312000, China

    Lan Luo

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  1. Rui Li
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Contributions

Rui Li: methodology, investigation, data curation, formal analysis, and writing—original draft. Guiping Wang: methodology, investigation, data curation, formal analysis, and writing—review and editing. Ruitong Liu: investigation, data curation, and formal analysis. Lan Luo: data curation and writing—review and editing. Ying Zhang: investigation and writing—review and editing. Zhongxiao Wan: conceptualization, methodology, funding acquisition, project administration, and writing—review and editing.

Corresponding author

Correspondence to Zhongxiao Wan.

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The authors declare no competing interests.

Ethical approval

The whole procedure abided by the Guidelines in the Care and Use of Animals and was approved by the Animal Studies Committee of Soochow University (approval no. SUDA20211206A02).

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The authors declare that all data were generated in-house and that no paper mill was used.

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Key points

1. Vitamin D-deficient diet mice had elevated fasting insulin and HOMA-IR at ZT13.

2. Vitamin D-deficient diet mice had disordered hepatic circadian rhythm.

3. Quercetin improved disordered hepatic circadian rhythm post vitamin D-deficient diet.

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Li, R., Wang, G., Liu, R. et al. Quercetin improved hepatic circadian rhythm dysfunction in middle-aged mice fed with vitamin D-deficient diet. J Physiol Biochem 80, 137–147 (2024). https://doi.org/10.1007/s13105-023-00990-0

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