Abstract
The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ando, H., Yanagihara, H., Hayashi, Y., Obi, Y., Tsuruoka, S., Takamura, T., Kaneko, S., and Fujimura, A. (2005). Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 146, 5631–5636.
Balsalobre, A., Brown, S.A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H.M., Schütz, G., and Schibler, U. (2000). Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289, 2344–2347.
Bray, M.S., and Young, M.E. (2007). Circadian rhythms in the development of obesity: potential role for the circadian clock within the adipocyte. Obes. Rev. 8, 169–181.
Bray, M.S., Shaw, C.A., Moore, M.W.S., Garcia, R.A.P., Zanquetta, M.M., Durgan, D.J., Jeong, W.J., Tsai, J.-Y., Bugger, H., Zhang, D., et al. (2008). Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Am. J. Physiol. Heart Circ. Physiol. 294, H1036–1047.
Buijs, R.M., Scheer, F.A., Kreier, F., Yi, C., Bos, N., Goncharuk, V.D., and Kalsbeek, A. (2006). Organization of circadian functions: interaction with the body. Prog. Brain Res. 153, 341–360.
Canaple, L., Rambaud, J., Dkhissi-Benyahya, O., Rayet, B., Tan, N.S., Michalik, L., Delaunay, F., Wahli, W., and Laudet, V. (2006). 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. 20, 1715–1727.
Damiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., and Schibler, U. (2000). Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev. 14, 2950–2961.
Dioum, E.M., Rutter, J., Tuckerman, J.R., Gonzalez, G., Gilles-Gonzalez, M.A., and McKnight, S.L. (2002). NPAS2: a gasresponsive transcription factor. Science 298, 2385–2387.
Duffield, G.E. (2003). DNA microarray analyses of circadian timing: the genomic basis of biological time. J. Neuroendocrinol. 15, 991–1002.
Fontaine, C., Dubois, G., Duguay, Y., Helledie, T., Vu-Dac, N., Gervois, P., Soncin, F., Mandrup, S., Fruchart, J.C., Fruchart-Najib, J., et al. (2003). 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. 278, 37672–37680.
Foster, R.G., and Hankins, M.W. (2007). Circadian vision. Curr. Biol. 17, R746–751.
Gervois, P., Chopin-Delannoy, S., Fadel, A., Dubois, G., Kosykh, V., Fruchart, J.C., Najib, J., Laudet, V., and Staels, B. (1999). Fibrates increase human REV-ERBalpha expression in liver via a novel peroxisome proliferator-activated receptor response element. Mol. Endocrinol. 13, 400–409.
Goh, B.C., Wu, X., Evans, A.E., Johnson, M.L., Hill, M.R., and Gimble, J.M. (2007). Food entrainment of circadian gene expression altered in PPARalpha-/- brown fat and heart. Biochem. Biophys. Res. Commun. 360, 828–833.
Green, C.B., Takahashi, J.S., and Bass, J. (2008). The meter of metabolism. Cell 134, 728–742.
Harmer, S.L., Panda, S., and Kay, S.A. (2001). Molecular bases of circadian rhythms. Annu. Rev. Cell Dev. Biol. 17, 215–253.
Inoue, I., Shinoda, Y., Ikeda, M., Hayashi, K., Kanazawa, K., Nomura, M., Matsunaga, T., Xu, H., Kawai, S., Awata, T., et al. (2005). CLOCK/BMAL1 is involved in lipid metabolism via transactivation of the peroxisome proliferator-activated receptor (PPAR) response element. J. Atheroscler. Thromb. 12, 169–174.
Ishida, A., Mutoh, T., Ueyama, T., Bando, H., Masubuchi, S., Nakahara, D., Tsujimoto, G., and Okamura, H. (2005). Light activates the adrenal gland: timing of gene expression and glucocorticoid release. Cell Metab. 2, 297–307.
Kaasik, K., and Lee, C.C. (2004). Reciprocal regulation of haem biosynthesis and the circadian clock in mammals. Nature 430, 467–471.
Kaneko, K., Yamada, T., Tsukita, S., Takahashi, K., Ishigaki, Y., Oka, Y., and Katagiri, H. (2009). Obesity alters circadian expressions of molecular clock genes in the brainstem. Brain Res. 1263, 58–68.
Kawamoto, T., Noshiro, M., Furukawa, M., Honda, K.K., Nakashima, A., Ueshima, T., Usui, E., Katsura, Y., Fujimoto, K., Honma, S., et al. (2006). Effects of fasting and re-feeding on the expression of Dec1, Per1, and other clock-related genes. J. Biochem. 140, 401–408.
Ko, C.H., and Takahashi, J.S. (2006). Molecular components of the mammalian circadian clock. Hum. Mol. Genet. 15, R271–277.
Kohsaka, A., Laposky, A.D., Ramsey, K.M., Estrada, C., Joshu, C., Kobayashi, Y., Turek, F.W., and Bass, J. (2007). High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab. 6, 414–421.
Kondratov, R.V., Kondratova, A.A., Gorbacheva, V.Y., Vykhovanets, O.V., and Antoch, M.P. (2006). Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev. 20, 1868–1873.
Lamia, K.A., Storch, K.-F., and Weitz, C.J. (2008). Physiological significance of a peripheral tissue circadian clock. Proc. Natl. Acad. Sci. USA 105, 15172–15177.
Laposky, A.D., Shelton, J., Bass, J., Dugovic, C., Perrino, N., and Turek, F.W. (2006). Altered sleep regulation in leptin-deficient mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R894–903.
Laposky, A.D., Bass, J., Kohsaka, A., and Turek, F.W. (2008). Sleep and circadian rhythms: key components in the regulation of energy metabolism. FEBS Lett. 582, 142–151.
Lau, P., Nixon, S.J., Parton, R.G., and Muscat, G.E. (2004). RORalpha regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells: caveolin-3 and CPT-1 are direct targets of ROR. J. Biol. Chem. 279, 36828–36840.
Le Minh, N., Damiola, F., Tronche, F., Schutz, G., and Schibler, U. (2001). Glucocorticoid hormones inhibit food-induced phaseshifting of peripheral circadian oscillators. EMBO J. 20, 7128–7136.
Lefebvre, P., Chinetti, G., Fruchart, J.C., and Staels, B. (2006). Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J. Clin. Invest. 116, 571–580.
Levi, F., and Schibler, U. (2007). Circadian rhythms: mechanisms and therapeutic implications. Annu. Rev. Pharmacol. Toxicol. 47, 593–628.
Lin, J., Handschin, C., and Spiegelman, B.M. (2005). Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 1, 361–370.
Liu, C., Li, S., Liu, T., Borjigin, J., and Lin, J.D. (2007). Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism. Nature 447, 477–481.
Michael, T.P., Salome, P.A., Yu, H.J., Spencer, T.R., Sharp, E.L., McPeek, M.A., Alonso, J.M., Ecker, J.R., and McClung, C.R. (2003). Enhanced fitness conferred by naturally occurring variation in the circadian clock. Science 302, 1049–1053.
Mistlberger, R.E. (2005). Circadian regulation of sleep in mammals: Role of the suprachiasmatic nucleus. Brain Res. Rev. 49, 429–454.
Nakahata, Y., Sahar, S., Astarita, G., Kaluzova, M., and Sassone-Corsi, P. (2009). Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324, 654–657.
Oster, H., and Foster, R.G. (2008). The interaction of light and the circadian clock network–a new therapeutic approach for the treatment of neuropsychiatric disorders? In Progress in Circadian Rhythms Research, A.-L. Léglise, ed. (Hauppauge, NY: Nova Science Publishers), pp. 35–65.
Oster, H., Damerow, S., Kiessling, S., Jakubcakova, V., Abraham, D., Tian, J., Hoffmann, M.W., and Eichele, G. (2006). The circadian rhythm of glucocorticoids is regulated by a gating mechanism residing in the adrenal cortical clock. Cell Metab. 4, 163–173.
Pan, X., and Hussain, M.M. (2009). Clock is important for food and circadian regulation of macronutrient absorption in mice. J. Lipid Res. [Epub ahead of print]
Pittendrigh, C.S. (1993). Temporal organization: reflections of a Darwinian clock-watcher. Annu. Rev. Physiol. 55, 16–54.
Preitner, N., Damiola, F., Lopez-Molina, L., Zakany, J., Duboule, D., Albrecht, U., and Schibler, U. (2002). The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110, 251–260.
Ramsey, K.M., Yoshino, J., Brace, C.S., Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H.K., Chong, J.L., Buhr, E.D., Lee, C., et al. (2009). Circadian clock feedback cycle through NAMPTmediated NAD+ biosynthesis. Science 324, 651–654.
Raspe, E., Duez, H., Mansen, A., Fontaine, C., Fievet, C., Fruchart, J.-C., Vennstrom, B., and Staels, B. (2002). Identification of Reverb{alpha} as a physiological repressor of apoC-III gene transcription. J. Lipid Res. 43, 2172–2179.
Resnick, H.E., Redline, S., Shahar, E., Gilpin, A., Newman, A., Walter, R., Ewy, G.A., Howard, B.V., and Punjabi, N.M. (2003). Diabetes and sleep disturbances: findings from the Sleep Heart Health Study. Diabetes Care 26, 702–709.
Rudic, R.D., McNamara, P., Curtis, A.M., Boston, R.C., Panda, S., Hogenesch, J.B., and Fitzgerald, G.A. (2004). BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2, e377.
Rutter, J., Reick, M., Wu, L.C., and McKnight, S.L. (2001). Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293, 510–514.
Sato, T.K., Panda, S., Miraglia, L.J., Reyes, T.M., Rudic, R.D., McNamara, P., Naik, K.A., FitzGerald, G.A., Kay, S.A., and Hogenesch, J.B. (2004). A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 43, 527–537.
Scott, E.M., Carter, A.M., and Grant, P.J. (2007). Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int. J. Obes. 32, 658–662.
Shea, S.A., Hilton, M.F., Orlova, C., Ayers, R.T., and Mantzoros, C.S. (2005). Independent circadian and sleep/wake regulation of adipokines and glucose in humans. J. Clin. Endocrinol. Metab. 90, 2537–2544.
Shimba, S., Ishii, N., Ohta, Y., Ohno, T., Watabe, Y., Hayashi, M., Wada, T., Aoyagi, T., and Tezuka, M. (2005). Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc. Natl. Acad. Sci. USA 102, 12071–12076.
Spanagel, R., Pendyala, G., Abarca, C., Zghoul, T., Sanchis-Segura, C., Magnone, M.C., Lascorz, J., Depner, M., Holzberg, D., Soyka, M., et al. (2005). The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Nat. Med. 11, 35–42.
Spiegel, K., Leproult, R., and Van Cauter, E. (1999). Impact of sleep debt on metabolic and endocrine function. Lancet 354, 1435–1439
Spiegel, K., Tasali, E., Penev, P., and Cauter, E.V. (2004). Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann. Intern. Med. 141, 846–850.
Stratmann, M., and Schibler, U. (2006). Properties, entrainment, and physiological functions of Mammalian peripheral oscillators. J. Biol. Rhythms 21, 494–506.
Takahashi, J.S., Hong, H.K., Ko, C.H., and McDearmon, E.L. (2008). The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat. Rev. Genet. 9, 764–775.
Turek, F.W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D.R., et al. (2005). Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308, 1043–1045.
Van Cauter, E., Polonsky, K.S., and Scheen, A.J. (1997). Roles of circadian rhythmicity and sleep in human glucose regulation. Endocr. Rev. 18, 716–738.
Wang, J., and Lazar, M.A. (2008). Bifunctional role of Rev-erbalpha in adipocyte differentiation. Mol. Cell. Biol. 28, 2213–2220.
Wittmann, M., Dinich, J., Merrow, M., and Roenneberg, T. (2006). Social jetlag: misalignment of biological and social time. Chronobiol. Int. 23, 497–509.
Woelfle, M.A., Ouyang, Y., Phanvijhitsiri, K., and Johnson, C.H. (2004). The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Curr. Biol. 14, 1481–1486.
Woon, P.Y., Kaisaki, P.J., Braganca, J., Bihoreau, M.-T., Levy, J.C., Farrall, M., and Gauguier, D. (2007). Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc. Natl. Acad. Sci. USA 104, 14412–14417.
Yang, X., Downes, M., Yu, R.T., Bookout, A.L., He, W., Straume, M., Mangelsdorf, D.J., and Evans, R.M. (2006). Nuclear receptor expression links the circadian clock to metabolism. Cell 126, 801–810.
Yang, S., Liu, A., Weidenhammer, A., Cooksey, R.C., McClain, D., Kim, M.K., Aguilera, G., Abel, E.D., and Chung, J.H. (2009). The role of mPer2 Clock gene in glucocorticoid and feeding rhythms. Endocrinology 150, 2153–2160.
Yildiz, B.O., Suchard, M.A., Wong, M.L., McCann, S.M., and Licinio, J. (2004). Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. Proc. Natl. Acad. Sci. USA 101, 10434–10439.
Yin, L., Wu, N., Curtin, J.C., Qatanani, M., Szwergold, N.R., Reid, R.A., Waitt, G.M., Parks, D.J., Pearce, K.H., Wisely, G.B., et al. (2007). Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science 318, 1786–1789.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Kovac, J., Husse, J. & Oster, H. A time to fast, a time to feast: The crosstalk between metabolism and the circadian clock. Mol Cells 28, 75–80 (2009). https://doi.org/10.1007/s10059-009-0113-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10059-009-0113-0