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Article | Open Access

Deficiency of circadian gene Per2 blocks luteolin-induced adipocyte browning in mice through weakening liver PPARα/RXRα/FGF21 pathway

Shanshan Shuia,b,1, Juan Chena,1, Yan Lina, Jingjing Yuana, Xin Wanga, Xian Zhanga, Jian Liua,c( ), Lei Zhenga,c( )
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, College of Food Science and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China
Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230009, China

1 These authors contributed equally to this work.

Peer review under responsibility of Beijing Academy of Food Sciences.

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Graphical Abstract

Abstract

During the development of diet-induced obesity, the change of energy matebolism is closely related to the function of the circadian clock in mammals. Luteolin (LU), one of the most common natural flavonoids riched in many edible plants, can ameliorate obesity by activating adipose tissue browning, but its effect on circadian clock in this process remains poorly understood. Here we found that dietary LU improved circadian misalignment of energy expenditure in high-fat diet (HFD)-fed wild-type (WT) mice. Moreover, dietary LU efficiently elevated uncoupling protein 1 levels in adipose tissue during the dark period, which was similar to the LU-increased hepatic PER2 expressions. Hepatic peroxisome proliferators-activated receptors α (PPARα)/recombinant retinoid X receptor α (RXRα)/fibroblast growth factor 21 (FGF21) pathway was rhythmically elevated by dietary LU in HFD-fed WT mice, whereas the promotion was inhibited in Per2-/- mice. Meanwhile, Per2 deletion abolished the effects of dietary LU on adipose tissue browning in HFD-fed mice. Further, LU treatment directly activated PPARα/RXRα/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2-/- mice. Taken together, the deletion of the core clock component Per2 impedes LU-induced adipose tissue browning through weakening PPARα/RXRα/FGF21 pathway in mice, providing a new insight into the interplay of energy metabolism and circadian clock for the anti-obesity activity of LU.

Keywords

ObesityCircadian clockLuteolinPer2 geneAdipose tissue browning

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Food Science and Human Wellness
Volume 14 Issue 3,
March 2025
Article number: 9250058
DOI: 10.26599/FSHW.2024.9250058
Cite this article:
Shui S, Chen J, Lin Y, et al. Deficiency of circadian gene Per2 blocks luteolin-induced adipocyte browning in mice through weakening liver PPARα/RXRα/FGF21 pathway. Food Science and Human Wellness, 2025, 14(3): 9250058. https://doi.org/10.26599/FSHW.2024.9250058

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Received: 08 June 2023
Revised: 19 June 2023
Accepted: 10 August 2023
Published: 18 March 2025
© 2025 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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