PER1 Phosphorylation Specifies Feeding Rhythm in Mice

Abstract

Organization of circadian behavior, physiology, and metabolism is important for human health. An S662G mutation in hPER2 has been linked to familial advanced sleep-phase syndrome (FASPS). Although the paralogous phosphorylation site S714 in PER1 is conserved in mice, its specific function in circadian organization remains unknown. Here, we find that the PER1S714G mutation accelerates the molecular feedback loop. Furthermore, hPER1S714G mice, but not hPER2S662G mice, exhibit peak time of food intake that is several hours before daily energy expenditure peaks. Both the advanced feeding behavior and the accelerated clock disrupt the phase of expression of several key metabolic regulators in the liver and adipose tissue. Consequently, hPER1S714G mice rapidly develop obesity on a high-fat diet. Our studies demonstrate that PER1 and PER2 are linked to different downstream pathways and that PER1 maintains coherence between the circadian clock and energy metabolism.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJhZjdkYjVlYzFmYTY4YjNhZmQwNjc1Y2FlMzhiZWI0ZSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjY2MjM1NzQ1fQ.g04Mz_3MW3HvGBxPJp-HPFI9WDKEMuPKpuikbR6qMA4IE0_qf0vTzyvRsk19SW4e4ty7QVuWjSO2KRy-yPVFL6OmG1GONGX1I2iJ9UKmKNmAPyYQQltEwD7xRau8HGx1I7g2vp7mSEVKHZNyc4plYmYNlRNPID4mLvEdB4GiAZ6CSFFUWO2Wshgdvreew44ShzCeJ5KC5kKrlG8SYx8IluTaGpsqwX5XzqNKHWiXSD6GE0IWuQPyHt2knKvvVckpYm9eXmDVBxxZL-PQgzC7CbGE3U50vmkqkvUAIWr2tt65NXmjawlIW14WvYExSSqQTYJQ2KdRB_uACGBrwkZXSg(mp4, (48.96 MB) Download video