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PMID: 22169754 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Regulation of metabolism: the circadian clock dictates the time.

Trends in endocrinology and metabolism: TEM ·Vol. 23 ·No. 1 ·2012-01-00 ·Pages 1-8

Sahar S, Sassone-Corsi P

Abstract

Circadian rhythms occur with a periodicity of approximately 24h and regulate a wide array of metabolic and physiologic functions. Accumulating epidemiological and genetic evidence indicates that disruption of circadian rhythms can be directly linked to many pathological conditions, including sleep disorders, depression, metabolic syndrome and cancer. Intriguingly, several molecular gears constituting the clock machinery have been found to establish functional interplays with regulators of cellular metabolism. Although the circadian clock regulates multiple metabolic pathways, metabolite availability and feeding behavior can in turn regulate the circadian clock. An in-depth understanding of this reciprocal regulation of circadian rhythms and cellular metabolism may provide insights into the development of therapeutic intervention against specific metabolic disorders.

MeSH Terms
Animals Chronobiology Disorders/metabolism Circadian Clocks Circadian Rhythm Circadian Rhythm Signaling Peptides and Proteins/metabolism Energy Metabolism Humans Metabolome
Chemicals
Circadian Rhythm Signaling Peptides and Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sahar Saurabh
Center for Epigenetics and Metabolism, School of Medicine, University of California, Irvine, CA 92697, USA.
Sassone-Corsi Paolo
References (84)
84 references, click to expand
  1. The clock gene Per2 links the circadian system to the estrogen receptor.
    Oncogene. 2007 Dec 13;26(57):7916-20 PMID: 17599055
  2. Transcriptional coregulators in the control of energy homeostasis.
    Trends Cell Biol. 2007 Jun;17(6):292-301 PMID: 17475497
  3. Comparison between morning and evening doses of simvastatin in hyperlipidemic subjects. A double-blind comparative study.
    Arterioscler Thromb. 1991 Jul-Aug;11(4):816-26 PMID: 2065035
  4. The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors.
    Genes Dev. 2010 Feb 15;24(4):345-57 PMID: 20159955
  5. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation.
    Science. 2009 Oct 16;326(5951):437-40 PMID: 19833968
  6. The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice.
    J Clin Invest. 2009 Aug;119(8):2423-34 PMID: 19587447
  7. Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6.
    Nat Med. 2010 Jan;16(1):67-74 PMID: 20023637
  8. Molecular clock is involved in predictive circadian adjustment of renal function.
    Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16523-8 PMID: 19805330
  9. Metabolic control through the PGC-1 family of transcription coactivators.
    Cell Metab. 2005 Jun;1(6):361-70 PMID: 16054085
  10. Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes.
    Curr Biol. 2011 Aug 23;21(16):1347-55 PMID: 21820310
  11. PER2 controls lipid metabolism by direct regulation of PPARγ.
    Cell Metab. 2010 Nov 3;12(5):509-20 PMID: 21035761
  12. SIRT1 regulates circadian clock gene expression through PER2 deacetylation.
    Cell. 2008 Jul 25;134(2):317-28 PMID: 18662546
  13. Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity.
    Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9888-93 PMID: 17517647
  14. PGC-1beta controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis.
    Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5223-8 PMID: 17360356
  15. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator.
    Cell. 2002 Jul 26;110(2):251-60 PMID: 12150932
  16. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control.
    Cell. 2008 Jul 25;134(2):329-40 PMID: 18662547
  17. Mop3 is an essential component of the master circadian pacemaker in mammals.
    Cell. 2000 Dec 22;103(7):1009-17 PMID: 11163178
  18. AMPK regulates circadian rhythms in a tissue- and isoform-specific manner.
    PLoS One. 2011 Mar 31;6(3):e18450 PMID: 21483791
  19. Cell biology of heme.
    Am J Med Sci. 1999 Oct;318(4):241-56 PMID: 10522552
  20. Reciprocal regulation of brain and muscle Arnt-like protein 1 and peroxisome proliferator-activated receptor alpha defines a novel positive feedback loop in the rodent liver circadian clock.
    Mol Endocrinol. 2006 Aug;20(8):1715-27 PMID: 16556735
  21. Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
    Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21453-8 PMID: 19940241
  22. Circadian rhythm gene period 3 is an inhibitor of the adipocyte cell fate.
    J Biol Chem. 2011 Mar 18;286(11):9063-70 PMID: 21228270
  23. Mammalian sirtuins: biological insights and disease relevance.
    Annu Rev Pathol. 2010;5:253-95 PMID: 20078221
  24. Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways.
    Science. 2007 Dec 14;318(5857):1786-9 PMID: 18006707
  25. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism.
    Science. 2011 Mar 11;331(6022):1315-9 PMID: 21393543
  26. Statins and cancer prevention.
    Nat Rev Cancer. 2005 Dec;5(12):930-42 PMID: 16341084
  27. Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha.
    Circulation. 1998 Dec 15;98(24):2738-43 PMID: 9851961
  28. Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells.
    Mol Cell Biol. 2002 Mar;22(6):1693-703 PMID: 11865049
  29. Measurement of internal body time by blood metabolomics.
    Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9890-5 PMID: 19487679
  30. Circadian timing of food intake contributes to weight gain.
    Obesity (Silver Spring). 2009 Nov;17(11):2100-2 PMID: 19730426
  31. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity.
    Nature. 2009 Apr 23;458(7241):1056-60 PMID: 19262508
  32. CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPARalpha) in mice.
    Biochem J. 2005 Mar 15;386(Pt 3):575-81 PMID: 15500444
  33. The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation.
    J Biol Chem. 2003 Sep 26;278(39):37672-80 PMID: 12821652
  34. NPAS2: a gas-responsive transcription factor.
    Science. 2002 Dec 20;298(5602):2385-7 PMID: 12446832
  35. Nuclear receptors: decoding metabolic disease.
    FEBS Lett. 2008 Jan 9;582(1):2-9 PMID: 18023286
  36. Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta.
    Nat Struct Mol Biol. 2007 Dec;14(12):1207-13 PMID: 18037887
  37. Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation.
    Aging (Albany NY). 2011 Aug;3(8):794-802 PMID: 21937766
  38. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase.
    Nature. 2000 Feb 17;403(6771):795-800 PMID: 10693811
  39. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.
    Nature. 2001 Sep 13;413(6852):131-8 PMID: 11557972
  40. Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation.
    Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3342-7 PMID: 17360649
  41. Obesity and metabolic syndrome in circadian Clock mutant mice.
    Science. 2005 May 13;308(5724):1043-5 PMID: 15845877
  42. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus.
    Genes Dev. 2000 Dec 1;14(23):2950-61 PMID: 11114885
  43. SIRT1 deacetylates and positively regulates the nuclear receptor LXR.
    Mol Cell. 2007 Oct 12;28(1):91-106 PMID: 17936707
  44. Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis.
    Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12071-6 PMID: 16093318
  45. Physiological significance of a peripheral tissue circadian clock.
    Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15172-7 PMID: 18779586
  46. Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology.
    Nature. 2008 Dec 18;456(7224):997-1000 PMID: 19037247
  47. cAMP-dependent signaling as a core component of the mammalian circadian pacemaker.
    Science. 2008 May 16;320(5878):949-53 PMID: 18487196
  48. Light at night increases body mass by shifting the time of food intake.
    Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18664-9 PMID: 20937863
  49. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.
    Science. 2009 May 1;324(5927):651-4 PMID: 19299583
  50. Reciprocal regulation of haem biosynthesis and the circadian clock in mammals.
    Nature. 2004 Jul 22;430(6998):467-71 PMID: 15269772
  51. Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes.
    Science. 2005 Nov 18;310(5751):1152-8 PMID: 16254148
  52. Circadian regulation of renal function.
    Kidney Int. 2010 Oct;78(7):640-5 PMID: 20664559
  53. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.
    PLoS Biol. 2005 Apr;3(4):e101 PMID: 15760270
  54. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice.
    Cell. 2004 Oct 1;119(1):121-35 PMID: 15454086
  55. The hypocretins as sensors for metabolism and arousal.
    J Physiol. 2009 Jan 15;587(1):33-40 PMID: 19047201
  56. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes.
    Nature. 2010 Jul 29;466(7306):627-31 PMID: 20562852
  57. SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein.
    J Biol Chem. 2005 Jul 22;280(29):26863-72 PMID: 15917222
  58. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1.
    Science. 2009 May 1;324(5927):654-7 PMID: 19286518
  59. An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice.
    Diabetologia. 2011 Jan;54(1):120-4 PMID: 20890745
  60. Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2.
    J Biol Chem. 2007 Jul 20;282(29):20794-8 PMID: 17525164
  61. Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha.
    Cell. 2005 Aug 26;122(4):505-15 PMID: 16122419
  62. Conserved metabolic regulatory functions of sirtuins.
    Cell Metab. 2008 Feb;7(2):104-12 PMID: 18249170
  63. The circadian clock interacts with metabolic physiology to influence reproductive fitness.
    Cell Metab. 2011 Jun 8;13(6):639-54 PMID: 21641546
  64. Adverse metabolic and cardiovascular consequences of circadian misalignment.
    Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4453-8 PMID: 19255424
  65. Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism.
    Nature. 2007 May 24;447(7143):477-81 PMID: 17476214
  66. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.
    Nature. 2005 Mar 3;434(7029):113-8 PMID: 15744310
  67. High-fat diet disrupts behavioral and molecular circadian rhythms in mice.
    Cell Metab. 2007 Nov;6(5):414-21 PMID: 17983587
  68. Coordinated transcription of key pathways in the mouse by the circadian clock.
    Cell. 2002 May 3;109(3):307-20 PMID: 12015981
  69. Metabolism control by the circadian clock and vice versa.
    Nat Struct Mol Biol. 2009 May;16(5):462-7 PMID: 19421159
  70. Nuclear receptor expression links the circadian clock to metabolism.
    Cell. 2006 Aug 25;126(4):801-10 PMID: 16923398
  71. Regulation of intracellular levels of NAD: a novel role for CD38.
    Biochem Biophys Res Commun. 2006 Jul 14;345(4):1386-92 PMID: 16730329
  72. Identification of Rev-erbalpha as a physiological repressor of apoC-III gene transcription.
    J Lipid Res. 2002 Dec;43(12):2172-9 PMID: 12454280
  73. Glucagon and regulation of glucose metabolism.
    Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E671-8 PMID: 12626323
  74. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis.
    PLoS Biol. 2004 Nov;2(11):e377 PMID: 15523558
  75. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27,485 people.
    Occup Environ Med. 2001 Nov;58(11):747-52 PMID: 11600731
  76. Hemin enhances the differentiation of mouse 3T3 cells to adipocytes.
    Cell. 1981 Oct;26(1 Pt 1):117-22 PMID: 6799206
  77. Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis.
    Nat Med. 2010 Oct;16(10):1152-6 PMID: 20852621
  78. Active and inactive forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver of the rat. Comparison with the rate of cholesterol synthesis in different physiological states.
    J Biol Chem. 1979 Jun 25;254(12):5144-9 PMID: 376507
  79. Metabolism and cancer: the circadian clock connection.
    Nat Rev Cancer. 2009 Dec;9(12):886-96 PMID: 19935677
  80. Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus.
    Curr Biol. 2002 Apr 2;12(7):540-50 PMID: 11937022
  81. CLOCK-mediated acetylation of BMAL1 controls circadian function.
    Nature. 2007 Dec 13;450(7172):1086-90 PMID: 18075593
  82. Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes.
    J Biol Chem. 2005 May 27;280(21):20589-95 PMID: 15788402
  83. The need to feed: homeostatic and hedonic control of eating.
    Neuron. 2002 Oct 10;36(2):199-211 PMID: 12383777
  84. Rotating shift work and the metabolic syndrome: a prospective study.
    Int J Epidemiol. 2009 Jun;38(3):848-54 PMID: 19129266
Article Info
Journal
Trends in endocrinology and metabolism: TEM
Abbr.
Trends Endocrinol Metab
ISSN
1879-3061
DOI
10.1016/j.tem.2011.10.005
Published
2012-01-00
Epub
2011-00-12
Pages
1-8
Language
English
Region
United States
NLM ID
9001516
PMCID
PMC3259741
Subset
IM
Grants
NIA NIH HHS · R21 AG033888 · United States
NIA NIH HHS · R21 AG041504-02 · United States
NIGMS NIH HHS · R01 GM081634 · United States
NIA NIH HHS · R21 AG041504 · United States
NIA NIH HHS · R21 AG033888-02 · United States
NIGMS NIH HHS · R01 GM081634-04 · United States
External Links
PubMed source DOI: 10.1016/j.tem.2011.10.005 PMC Full Text View journal details
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