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

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.

Keywords: Circadian rhythm; Insulin signaling; Quercetin; Vitamin D.