title: 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.
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cambridge Suda Genome Resource Center, Soochow University, Suzhou 215006, China.
authors.forename: Moli
authors.initials: M
authors.lastname: Huang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Guangsen
authors.initials: G
authors.lastname: Shi
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xing
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Qu
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Cambridge Suda Genome Resource Center, Soochow University, Suzhou 215006, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Cambridge Suda Genome Resource Center, Soochow University, Suzhou 215006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: panda@salk.edu.
authors.forename: Satchidananda
authors.initials: S
authors.lastname: Panda
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Cambridge Suda Genome Resource Center, Soochow University, Suzhou 215006, China; Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai 200433, China. Electronic address: yingxu@nju.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating; D004734:Energy Metabolism; D025461:Feedback, Physiological; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009765:Obesity / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: C539022:PER1 protein, human; C421902:PER2 protein, human; D056950:Period Circadian Proteins