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Feeding rhythm entrains circadian metabolism genes, but not the circadian clock, in brown adipose tissue

CHEN Jiang-Hui^1,2, ZHOU Mei-Yu², HUANG Rong-Feng², XIN Hao-Ran², CHENG Shu-Ting³, LI Min-Dian², TONG Shi-Fei^2,*

¹Department of Cardiology, the Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China；²Department of Cardiology and the Center for Circadian Metabolism and Cardiovascular Disease, the First Affiliated Hospital of Army Medical University, Chongqing 400038, China；³NHC Key Laboratory of Chronobiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China

Abstract

The central circadian clock and feeding rhythm coordinately reset peripheral circadian clocks. Emerging evidence suggests that feeding rhythm resets peripheral circadian clocks in a tissue-specific manner. This study aimed to determine whether and how feeding rhythm regulates circadian rhythms of the circadian clock and metabolic genes in brown adipose tissue (BAT). We applied different regimens of time-restricted feeding (TRF) in wildtype and Per1/2 deficient C57BL/6 mice, and quantified the effects of sex, treatment duration, constant light, and circadian clock on circadian rhythms of the BAT circadian clock and metabolic genes by RT-qPCR; Representative circadian clock genes are Bmal1, Nr1d1, Dbp, and Per2, and representative metabolic genes are uncoupling protein 1 (Ucp1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) that controls the flux through glycolysis, pyruvate dehydrogenase kinase isozyme 4 (Pdk4) gating the tricarboxylic acid cycle, and carnitine palmitoyltransferase 1A (Cpt1a) that controls mitochondrial fatty acid oxidation. The results showed that, daytime-restricted feeding (DRF) moderately shifted the phase of the BAT circadian clock in female mice within 7 or 36 d, and resulted in the loss of circadian rhythm in Dbp and Per2 transcripts in males. DRF induced de novo oscillation of the Ucp1 transcript, and shifted the phase of representative metabolic genes, such as Pfkfb3, Pdk4, and Cpt1a, more than 7 h. Constant light is known to disrupt the synchrony of the central circadian clock. The results showed that constant light promoted phase entrainment of the circadian clock by DRF in BAT, but abolished the oscillation of the metabolic genes (except for Pdk4). Despite combined treatment with Per1/2 deficiency and constant darkness, DRF was sufficient to drive circadian rhythms of Bmal1 and Dbp, but not those of Nr1d1, Ucp1, Pfkfb3, and Cpt1a. Overall, the circadian clock of BAT has weak adaptation to altered feeding rhythms and sex differences. The central circadian clock antagonizes DRF in the entrainment of the BAT circadian clock, whereas DRF resets circadian rhythms of metabolic genes, such as Ucp1, Pfkfb3, and Cpt1a, in a circadian clock-dependent manner.

Key words: circadian metabolism; time-restricted feeding; circadian clock; brown adipose tissue; uncoupling protein 1; glucose metabolism; lipid metabolism

Received: 　　Accepted:

Corresponding author: 仝识非　　E-mail: 651050@hospital.cqmu.edu.cn

DOI: 10.13294/j.aps.2022.0035

Citing This Article：

CHEN Jiang-Hui, ZHOU Mei-Yu, HUANG Rong-Feng, XIN Hao-Ran, CHENG Shu-Ting, LI Min-Dian, TONG Shi-Fei. Feeding rhythm entrains circadian metabolism genes, but not the circadian clock, in brown adipose tissue. Acta Physiol Sin 2022; 74 (5): 726-736 (in Chinese with English abstract).