title: Calorie restriction regulates circadian clock gene expression through BMAL1 dependent and independent mechanisms.
abstract: Feeding behavior, metabolism and circadian clocks are interlinked. Calorie restriction (CR) is a feeding paradigm known to extend longevity. We found that CR significantly affected the rhythms in the expression of circadian clock genes in mice on the mRNA and protein levels, suggesting that CR reprograms the clocks both transcriptionally and post-transcriptionally. The effect of CR on gene expression was distinct from the effects of time-restricted feeding or fasting. Furthermore, CR affected the circadian output through up- or down-regulation of the expression of several clock-controlled transcriptional factors and the longevity candidate genes. CR-dependent effects on some clock gene expression were impaired in the liver of mice deficient for BMAL1, suggesting importance of this transcriptional factor for the transcriptional reprogramming of the clock, however, BMAL1- independent mechanisms also exist. We propose that CR recruits biological clocks as a natural mechanism of metabolic optimization under conditions of limited energy resources.
authors.affiliation: Department of Biological, Geological, and Environmental Sciences and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Sonal A
authors.initials: SA
authors.lastname: Patel
authors.affiliation: Department of Biological, Geological, and Environmental Sciences and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Nikkhil
authors.initials: N
authors.lastname: Velingkaar
authors.affiliation: Department of Biological, Geological, and Environmental Sciences and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Makwana
authors.affiliation: Department of Biological, Geological, and Environmental Sciences and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Amol
authors.initials: A
authors.lastname: Chaudhari
authors.affiliation: Department of Biological, Geological, and Environmental Sciences and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Kondratov
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction / Q000009:adverse effects*; D057906:Circadian Clocks / Q000187:drug effects*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D005247:Feeding Behavior; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D051379:Mice; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D056925:Circadian Rhythm Signaling Peptides and Proteins; D056931:Cryptochromes; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; C538944:Clock protein, mouse