title: The biological clock is regulated by adrenergic signaling in brown fat but is dispensable for cold-induced thermogenesis.
abstract: The biological clock plays an important role in integrating nutrient and energy metabolism with other cellular processes. Previous studies have demonstrated that core clock genes are rhythmically expressed in peripheral tissues, including the liver, skeletal muscle, pancreatic islets, and white and brown adipose tissues. These peripheral clocks are entrained by physiological cues, thereby aligning the circadian pacemaker to tissue functions. The mechanisms that regulate brown adipose tissue clock in response to physiological signals remain poorly understood. Here we found that the expression of core clock genes is highly responsive to cold exposure in brown fat, but not in white fat. This cold-inducible regulation of the clock network is mediated by adrenergic receptor activation and the transcriptional coactivator PGC-1α. Brown adipocytes in mice lacking a functional clock contain large lipid droplets accompanied by dysregulation of genes involved in lipid metabolism and adaptive thermogenesis. Paradoxically, the "clockless" mice were competent in maintaining core body temperature during cold exposure. These studies elucidated the presence of adrenergic receptor/clock crosstalk that appears to be required for normal thermogenic gene expression in brown fat.
authors.affiliation: Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Yu
authors.forename: Guo-Xiao
authors.initials: GX
authors.lastname: Wang
authors.forename: Jiandie D
authors.initials: JD
authors.lastname: Lin
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks; D001831:Body Temperature; D002454:Cell Differentiation; D002940:Circadian Rhythm; D003080:Cold Temperature; D004149:Dioxoles / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016133:Polymerase Chain Reaction; D011941:Receptors, Adrenergic / Q000378:metabolism*; D015398:Signal Transduction; D022722:Thermogenesis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D004149:Dioxoles; D008055:Lipids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011941:Receptors, Adrenergic; D014157:Transcription Factors; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate