Deficiency of circadian gene Per2 blocks luteolin-induced adipocyte browning in mice through weakening liver PPARα/RXRα/FGF21 pathwayOA
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 receptorsα(PPARα)/recombinant retinoid X receptorα(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 LUinduced 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.
Shanshan Shui;Juan Chen;Yan Lin;Jingjing Yuan;Xin Wang;Xian Zhang;Jian Liu;Lei Zheng
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,ChinaSchool of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,ChinaSchool of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,ChinaSchool of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,ChinaSchool of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,ChinaSchool of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,ChinaSchool of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,China Engineering Research Center of Bio-process,Ministry of Education,Hefei University of Technology,Hefei 230009,ChinaSchool of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,China Engineering Research Center of Bio-process,Ministry of Education,Hefei University of Technology,Hefei 230009,China
预防医学
ObesityCircadian clockLuteolinPer2 geneAdipose tissue browning
《Food Science and Human Wellness》 2025 (3)
P.892-901,10
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