Publication Date:
2007-11-17
Description:
The circadian clock temporally coordinates metabolic homeostasis in mammals. Central to this is heme, an iron-containing porphyrin that serves as prosthetic group for enzymes involved in oxidative metabolism as well as transcription factors that regulate circadian rhythmicity. The circadian factor that integrates this dual function of heme is not known. We show that heme binds reversibly to the orphan nuclear receptor Rev-erbalpha, a critical negative component of the circadian core clock, and regulates its interaction with a nuclear receptor corepressor complex. Furthermore, heme suppresses hepatic gluconeogenic gene expression and glucose output through Rev-erbalpha-mediated gene repression. Thus, Rev-erbalpha serves as a heme sensor that coordinates the cellular clock, glucose homeostasis, and energy metabolism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yin, Lei -- Wu, Nan -- Curtin, Joshua C -- Qatanani, Mohammed -- Szwergold, Nava R -- Reid, Robert A -- Waitt, Gregory M -- Parks, Derek J -- Pearce, Kenneth H -- Wisely, G Bruce -- Lazar, Mitchell A -- R01 DK45586/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Dec 14;318(5857):1786-9. Epub 2007 Nov 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18006707" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Biological Clocks
;
Cell Line
;
Cell Line, Tumor
;
*Circadian Rhythm/genetics
;
DNA-Binding Proteins/*metabolism
;
Energy Metabolism
;
*Gene Expression Regulation
;
Gluconeogenesis/genetics
;
Glucose/*metabolism
;
Glucose-6-Phosphatase/genetics/metabolism
;
Heme/*metabolism
;
Hemin/pharmacology
;
Histone Deacetylases/metabolism
;
Homeostasis
;
Humans
;
Male
;
*Metabolic Networks and Pathways
;
Mice
;
Nuclear Proteins/metabolism
;
Nuclear Receptor Co-Repressor 1
;
Nuclear Receptor Subfamily 1, Group D, Member 1
;
Receptors, Cytoplasmic and Nuclear/*metabolism
;
Repressor Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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