Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock
Open accessAbstract
Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle.
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Disruption of the muscle clock has significant impact on glucose intolerance and insulin resistance with very small changes in fiber types.
“Disruption of the muscle clock has also been shown to have significant impact on glucose intolerance and insulin resistance with very small changes in fiber types (Dyar et al., 2014; Schroder et al., 2015; Harfmann et al., 2016).”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Dyar et al., 2014
Prolonged loss of Bmal1 function is associated with increased fibrosis within muscle.
“In addition, prolonged loss of Bmal1 function was also associated with increased fibrosis within the muscle.”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Dyar et al., 2014
Muscle-specific Bmal1 KO animals showed reduced protein levels of GLUT4 and an impaired insulin-stimulated glucose uptake in their muscles.
“These animals showed reduced protein levels of GLUT4 and an impaired insulin-stimulated glucose uptake in their muscles.”
From Circadian control of glucose metabolism (2014) · cites this paper as [153]
The skeletal muscle clock regulates glucose uptake and metabolism.
“For example, the hepatic clock regulates fasting glycemic control and glucose clearance (8), the pancreatic clock regulates insulin secretion and its response to glucose (9-11), the adipose clock regulates lipid storage and mobilization (12,13), and the skeletal muscle clock regulates glucose uptake and metabolism (14).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [14]
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“For example, the fact that Per2 oscillation was only mildly affected in mKO skeletal muscles likely reflects a role for oscillating systemic signals in the regulation of this gene, as was demonstrated in a liver-specific Bmal1 knockout [44,45].”
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Huang, W., Ramsey, K. M., Marcheva, B., & Bass, J. T. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46043 · Cited by 726 · cited 1× · see citing works
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“For example, the fact that Per2 oscillation was only mildly affected in mKO skeletal muscles likely reflects a role for oscillating systemic signals in the regulation of this gene, as was demonstrated in a liver-specific Bmal1 knockout [44,45].”
BackgroundCrosstalk between components of circadian and metabolic cycles in mammals
Asher, G., & Schibler, U. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.006 · Cited by 601 · cited 1× · see citing works
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BackgroundCryptochromes mediate rhythmic repression of the glucocorticoid receptor
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“intolerance [10,11]; Bmal1 null mice are also glucose intolerant, and show altered gluconeogenesis [10,12].”
BackgroundDeficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction
Sakamoto, K., McCarthy, A., Smith, D. P., Green, K. A., Hardie, D. G., Ashworth, A., & Alessi, D. R. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600667 · Cited by 538 · cited 1× · see citing works
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Obesity in mice with adipocyte-specific deletion of clock component Arntl
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“Animals Muscle-specific inactivation of Bmal1 (mKO) was obtained from the cross between a C57BL/6 mouse line with floxed Bmal1 [18] and a C57BL/6 mouse line carrying a Cre recombinase transgene under control of the Mlc1f promoter (Mlc1f–Cre) [19].”
BackgroundMethodCircadian Disruption Leads to Insulin Resistance and Obesity
Shi, S.-Q., Ansari, T. S., McGuinness, O. P., Wasserman, D. H., & Johnson, C. H. (2013) · Current Biology · doi:10.1016/j.cub.2013.01.048 · Cited by 452 · see citing works
Andrews, J. L., Zhang, X., McCarthy, J. J., McDearmon, E. L., Hornberger, T. A., Russell, B., Campbell, K. S., Arbogast, S., Reid, M. B., Walker, J. R., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014523107 · Cited by 389 · cited 2× · see citing works
“Changes in skeletal muscle structure and function were described in a global Bmal1 knockout model [41]; however it is unclear whether these are direct consequences of muscle Bmal1 deficiency or secondary effects due to the disruption of the circadian pacemaker or other peripheral clocks.”
BackgroundMuoio, D. M., Noland, R. C., Kovalik, J.-P., Seiler, S. E., Davies, M. N., DeBalsi, K. L., Ilkayeva, O. R., Stevens, R. D., Kheterpal, I., Zhang, J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.005 · Cited by 372 · cited 1× · see citing works
“Other experimental conditions, such as lipid infusion [61– 63], and skeletal muscle-specific genetic models, such as overexpression of PPARα [64] or inactivation of carnitine acetyltransferase [65], were also shown to cause muscle insulin resistance without affecting AKT phosphorylation.”
MethodCoordination of the transcriptome and metabolome by the circadian clock
Eckel‐Mahan, K. L., Patel, V. R., Mohney, R. P., Vignola, K. S., Baldi, P., & Sassone‐Corsi, P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118726109 · Cited by 370 · cited 1× · see citing works
“Global metabolic profiling Metabolic profiling, peak identification, and curation were performed by Metabolon using described methods [28].”
MethodIdentification of the circadian transcriptome in adult mouse skeletal muscle
McCarthy, J. J., Andrews, J. L., McDearmon, E. L., Campbell, K. S., Barber, B. K., Miller, B. H., Walker, J. R., Hogenesch, J. B., Takahashi, J. S., & Esser, K. A. (2007) · Physiological Genomics · doi:10.1152/physiolgenomics.00066.2007 · Cited by 363 · cited 2× · see citing works
“A similar shift in Pdk4 expression was previously observed in muscles from a global Clock mutant [55].”
BackgroundLipid-Induced Mitochondrial Stress and Insulin Action in Muscle
Muoio, D. M., & Neufer, P. D. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.010 · Cited by 343 · cited 1× · see citing works
“Skeletal muscles with functional clocks are thus primed to choose “the right fuel at the right time“ [70], whereas muscle-specific Bmal1 inactivation and the consequent disruption of the muscle clock would cause a state of reduced metabolic flexibility [71], characterized by muscle insulin resistance and altered gluco…”
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“It is likely that other insulin-sensitive tissues, such as adipose tissue, compensate for reduced muscle insulin sensitivity at the whole body level [59].”
BackgroundDissecting the Functions of the Mammalian Clock Protein BMAL1 by Tissue-Specific Rescue in Mice
McDearmon, E. L., Patel, K., Ko, C. H., Walisser, J. A., Schook, A. C., Chong, J. L., Wilsbacher, L. D., Song, E. J., Hong, H., Bradfield, C. A., et al. (2006) · Science · doi:10.1126/science.1132430 · Cited by 321 · cited 1× · see citing works
“Global Bmal1 knockout causes not only loss of circadian rhythm of locomotor activity but also reduced total activity levels [42] and rescue experiments in which BMAL1 was constitutively expressed in skeletal muscle of Bmal1 null mice showed that musclespecific rescue restored activity levels, though not circadian rhyt…”
BackgroundAnalysis of Gene Regulatory Networks in the Mammalian Circadian Rhythm
Yan, J., Wang, H., Liu, Y., & Shao, C. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000193 · Cited by 297 · cited 4× · see citing works
“Pdp1 was also previously reported to be a circadian gene in the brain (listed as Ppm2c ) [49].”
BackgroundInfluentialAS160 Regulates Insulin- and Contraction-stimulated Glucose Uptake in Mouse Skeletal Muscle
Kramer, H. F., Witczak, C. A., Taylor, E. B., FUJII, N. L., Hirshman, M. F., & Goodyear, L. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605461200 · Cited by 285 · cited 1× · see citing works
“AKT is known to control skeletal muscle glucose transport by phosphorylating the Rab-GTPase-activating proteins TBC1D4 (AS160) and TBC1D1, thus promoting the translocation of GLUT4 to the plasma membrane [46–48].”
BackgroundRegulation of Glucose Transporter Translocation in Health and Diabetes
Bogan, J. S. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060109-094246 · Cited by 279 · cited 3× · see citing works
“AKT is known to control skeletal muscle glucose transport by phosphorylating the Rab-GTPase-activating proteins TBC1D4 (AS160) and TBC1D1, thus promoting the translocation of GLUT4 to the plasma membrane [46 – 48].”
BackgroundFinck, B. N., Bernal-Mizrachi, C., Han, D. H., Coleman, T., Sambandam, N., LaRiviere, L. L., Holloszy, J. O., Semenkovich, C. F., & Kelly, D. P. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.01.006 · Cited by 270 · cited 2× · see citing works
“Other experimental conditions, such as lipid infusion [61 – 63], and skeletal muscle-speci fi c genetic models, such as overexpression of PPAR α [64] or inactivation of carnitine acetyltransferase [65], were also shown to cause muscle insulin resistance without affecting AKT phosphorylation.”
MethodBlaauw, B., Canato, M., Agatea, L., Toniolo, L., Mammucari, C., Masiero, E., Abraham, R., Sandri, M., Schiaffino, S., & Reggiani, C. (2009) · The FASEB Journal · doi:10.1096/fj.09-131870 · Cited by 244 · cited 1× · see citing works
“Force measurements In vivo force measurements were performed as described previously [22].”
MethodReinke, H., Saini, C., Fleury-Olela, F., Dibner, C., Benjamin, I. J., & Schibler, U. (2008) · Genes & Development · doi:10.1101/gad.453808 · Cited by 228 · cited 1× · see citing works
“Although a non-canonical E-Box, the core binding motif CACGGG was shown to efficiently bind the CLOCK:BMAL1 heterodimer in a screen for circadian transcription factor DNA binding activity [51].”
BackgroundProgressive arthropathy in mice with a targeted disruption of theMop3/Bmal-1 locus
Bunger, M. K., Walisser, J. A., Sullivan, R., Manley, P. A., Moran, S. M., Kalscheur, V. L., Colman, R. J., & Bradfield, C. A. (2005) · genesis · doi:10.1002/gene.20102 · Cited by 207 · cited 1× · see citing works
“Mice with whole body Bmal1 knockout were reported to stop growing around 16 weeks of age, display progressive arthropathy, sarcopenia and loss of fat tissue, and die between 26 and 52 weeks of age [39,40].”
BackgroundTbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity
Chadt, A., Leicht, K., Deshmukh, A. S., Jiang, L. Q., Scherneck, S., Bernhardt, U., Dreja, T., Vogel, H., Schmolz, K., Kluge, R., et al. (2008) · Nature Genetics · doi:10.1038/ng.244 · Cited by 201 · cited 10× · see citing works
“Tbc1d1 was previously identi fi ed as a circadian gene also in bone and atrial myocardium [49] and a comparative computational screen for conserved putative CLOCK:BMAL1-binding elements in the mouse and human genomes identi fi ed a potential cis -regulatory CLOCK:BMAL1 binding site within Tbc1d1 [50].”
BackgroundInfluentialRabøl, R., Petersen, K. F., Dufour, S., Flannery, C. A., & Shulman, G. I. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110105108 · Cited by 195 · cited 1× · see citing works
“Skeletal muscle is a major site of insulin-stimulated glucose disposal [56] and muscle insulin resistance has been considered to be one of the earliest factors in the pathogenesis of the metabolic syndrome [57].”
BackgroundRadioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle
Cederblad, G., Carlin, J. I., Constantin‐Teodosiu, D., Harper, P., & Hultman, E. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90292-h · Cited by 173 · cited 1× · see citing works
“All transcriptome and metabolome data are accessible through the CircadiOmics Website (http://circadiomics.igb.uci.edu), allowing users to search and view genes of interest and detected metabolites in Ctrl and Bmal1 mKO skeletal muscles, as well as their interactions and statistics.”
MethodPyruvate dehydrogenase activity and acetyl group accumulation during exercise after different diets
Putman, C. T., Spriet, L. L., Hultman, E., Lindinger, M. I., Lands, L. C., McKelvie, R. S., Cederblad, G., Jones, N. L., & Heigenhauser, G. J. F. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.265.5.e752 · Cited by 166 · cited 1× · see citing works
“All transcriptome and metabolome data are accessible through the CircadiOmics Website (http://circadiomics.igb.uci.edu), allowing users to search and view genes of interest and detected metabolites in Ctrl and Bmal1 mKO skeletal muscles, as well as their interactions and statistics.”
MethodCircadian Clock Gene Bmal1 Is Not Essential; Functional Replacement with its Paralog, Bmal2
Shi, S.-Q., Hida, A., McGuinness, O. P., Wasserman, D. H., Yamazaki, S., & Johnson, C. H. (2010) · Current Biology · doi:10.1016/j.cub.2009.12.034 · Cited by 150 · cited 1× · see citing works
“The Bmal1 paralog, Bmal2 (Arntl2/Mop9), which is downregulated in the liver of Bmal1 null mice [42] and can functionally replace Bmal1 [43], was found to be expressed at low levels without daily fluctuations in mouse skeletal muscle, and”
BackgroundA sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue
Constantin‐Teodosiu, D., Cederblad, G., & Hultman, E. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90437-x · Cited by 149 · cited 1× · see citing works
“All transcriptome and metabolome data are accessible through the CircadiOmics Website (http://circadiomics.igb.uci.edu), allowing users to search and view genes of interest and detected metabolites in Ctrl and Bmal1 mKO skeletal muscles, as well as their interactions and statistics.”
MethodTBC1D1 Regulates Insulin- and Contraction-Induced Glucose Transport in Mouse Skeletal Muscle
An, D., Toyoda, T., Taylor, E. B., Yu, H., Fujii, N., Hirshman, M. F., & Goodyear, L. J. (2010) · Diabetes · doi:10.2337/db09-1266 · Cited by 147 · cited 1× · see citing works
“AKT is known to control skeletal muscle glucose transport by phosphorylating the Rab-GTPase-activating proteins TBC1D4 (AS160) and TBC1D1, thus promoting the translocation of GLUT4 to the plasma membrane [46 – 48].”
BackgroundRole of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis during starvation
Jeoung, N. H., Wu, P., Joshi, M., Jaskiewicz, J. A., Bock, C. B., DePaoli-Roach, A. A., & Harris, R. A. (2006) · Biochemical Journal · doi:10.1042/bj20060125 · Cited by 143 · cited 1× · see citing works
“The method to measure glucose oxidation was similar to that previously described [34] with some modifications.”
MethodHøeg, L. D., Sjøberg, K. A., Jeppesen, J., Jensen, T. E., Frøsig, C., Birk, J. B., Bisiani, B., Hiscock, N., Pilegaard, H., Wojtaszewski, J. F. P., et al. (2011) · Diabetes · doi:10.2337/db10-0698 · Cited by 136 · see citing works
Self-citationCircadiOmics: integrating circadian genomics, transcriptomics, proteomics and metabolomics
Patel, V. R., Eckel‐Mahan, K. L., Sassone‐Corsi, P., & Baldi, P. (2012) · Nature Methods · doi:10.1038/nmeth.2111 · Cited by 118 · cited 1× · see citing works
“Networks and subnetworks can be explored and rearranged interactively, providing a comprehensive systems-level view of the circadian molecular pathways [29].”
BackgroundThe hypothalamic clock and its control of glucose homeostasis
Kalsbeek, A., Yi, C., la Fleur, S. E., & Fliers, E. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.02.005 · Cited by 106 · cited 5× · see citing works
“The hierarchical role of the central pacemaker was demonstrated by the finding that circadian rhythms of blood glucose, insulin and glucagon, as well as glucose tolerance, are all abolished by SCN lesion [14].”
BackgroundMethodInfluentialTemporally controlled targeted somatic mutagenesis in skeletal muscles of the mouse
Schuler, M. J., Ali, F., Metzger, E., Chambon, P., & METZGER, D. (2005) · genesis · doi:10.1002/gene.20107 · Cited by 101 · cited 2× · see citing works
“A second knockout model with inducible muscle-specific inactivation of Bmal1 (imKO) was obtained by crossing the Bmal1 floxed line with mice carrying an α-skeletal actin driven Cre recombinase fused to a mutated estrogen receptor [20], which can be activated by treatment with tamoxifen (i.”
BackgroundMethodHoy, A. J., Brandon, A. E., Turner, N., Watt, M. J., Bruce, C. R., Cooney, G. J., & Kraegen, E. W. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90945.2008 · Cited by 92 · cited 1× · see citing works
“Other experimental conditions, such as lipid infusion [61 – 63], and skeletal muscle-speci fi c genetic models, such as overexpression of PPAR α [64] or inactivation of carnitine acetyltransferase [65], were also shown to cause muscle insulin resistance without affecting AKT phosphorylation.”
MethodAnalysis and synthesis of high-amplitude Cis -elements in the mammalian circadian clock
Kumaki, Y., Ukai‐Tadenuma, M., Uno, K. D., Nishio, J., Masumoto, K., Nagano, M., Komori, T., Shigeyoshi, Y., Hogenesch, J. B., & Ueda, H. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802636105 · Cited by 77 · cited 12× · see citing works
“Tbc1d1 was previously identi fi ed as a circadian gene also in bone and atrial myocardium [49] and a comparative computational screen for conserved putative CLOCK:BMAL1-binding elements in the mouse and human genomes identi fi ed a potential cis -regulatory CLOCK:BMAL1 binding site within Tbc1d1 [50].”
BackgroundInfluentialThe Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism
Szekeres, F. L. M., Chadt, A., Tom, R. Z., Deshmukh, A. S., Chibalin, A., Björnholm, M., Al‐Hasani, H., & Zierath, J. R. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00605.2011 · Cited by 76 · cited 10× · see citing works
“Tbc1d1 was previously identi fi ed as a circadian gene also in bone and atrial myocardium [49] and a comparative computational screen for conserved putative CLOCK:BMAL1-binding elements in the mouse and human genomes identi fi ed a potential cis -regulatory CLOCK:BMAL1 binding site within Tbc1d1 [50].”
BackgroundInfluentialPDH-E1α Dephosphorylation and Activation in Human Skeletal Muscle During Exercise
Pilegaard, H., Birk, J. B., Sacchetti, M., Mourtzakis, M., Hardie, D. G., Stewart, G. A., Neufer, P. D., Saltin, B., van Hall, G., & Wojtaszewski, J. F. P. (2006) · Diabetes · doi:10.2337/db06-0152 · Cited by 74 · cited 2× · see citing works
“SDS-PAGE and western blotting Muscle lysates were prepared as previously reported [38], protein concentration determined using the bicinchoninic acid assay (Pierce, Rockford, IL, USA) and SDS-PAGE performed using 10% hand-cast gels.”
MethodDokas, J., Chadt, A., Nolden, T., Himmelbauer, H., Zierath, J. R., Joost, H., & Al‐Hasani, H. (2013) · Endocrinology · doi:10.1210/en.2012-2147 · Cited by 65 · cited 13× · see citing works
“AKT is known to control skeletal muscle glucose transport by phosphorylating the Rab-GTPase-activating proteins TBC1D4 (AS160) and TBC1D1, thus promoting the translocation of GLUT4 to the plasma membrane [46 – 48].”
BackgroundResultInfluentialMacKrell, J. G., & Cartee, G. D. (2012) · Diabetes · doi:10.2337/db11-1299 · Cited by 42 · cited 1× · see citing works
“The method to measure glucose transport was similar to that described previously [30,31] with some modifications [32].”
ResultFeneberg, R., & Lemmer, B. (2004) · Chronobiology International · doi:10.1081/cbi-200026958 · Cited by 40 · cited 1× · see citing works
“A circadian rhythm of glucose uptake was also demonstrated in muscle cell cultures, but these daily fluctuations were observed both in basal and insulinstimulated conditions [17].”
BackgroundWang, C. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.11.3621 · Cited by 29 · cited 1× · see citing works
“Muscles were quickly removed, rinsed in sterile saline, and washed 3 5 min (100 RPM) in ice-cold KHB to clear extracellular space of 2-DG [33].”
MethodPGC-1α increases PDH content but does not change acute PDH regulation in mouse skeletal muscle
Kiilerich, K., Adser, H., Jakobsen, A. H., Pedersen, P. A., Hardie, D. G., Wojtaszewski, J. F. P., & Pilegaard, H. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00400.2010 · Cited by 29 · cited 1× · see citing works
“a site that increases in skeletal muscle after fasting [54], was significantly increased in mKO muscles (Figure 5D).”
BackgroundEsquirol, Y., Bongard, V., Ferrières, J., Verdier, H., & Perret, B. (2012) · Chronobiology International · doi:10.3109/07420528.2012.719959 · Cited by 28 · see citing works
Alkhateeb, H. H., Chabowski, A., Glatz, J. F. C., Gurd, B. J., Luiken, J. J. F. P., & Bonen, A. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90908.2008 · Cited by 28 · cited 1× · see citing works
“Other experimental conditions, such as lipid infusion [61 – 63], and skeletal muscle-speci fi c genetic models, such as overexpression of PPAR α [64] or inactivation of carnitine acetyltransferase [65], were also shown to cause muscle insulin resistance without affecting AKT phosphorylation.”
MethodNiwa‐Kawakita, M., Abramowski, V., Kalamarides, M., Thomas, G. D., & Giovannini, M. (2000) · genesis · doi:10.1002/(sici)1526-968x(200002)26:2 · Cited by 22 · see citing works
Bryson, J. M., Cooney, G. J., Wensley, V. R., Blair, S. C., & Caterson, I. D. (1993) · Biochemical Journal · doi:10.1042/bj2950731 · Cited by 11 · cited 1× · see citing works
“Similar diurnal fluctuations in PDHa activity were also reported in cardiac muscle [53].”
Background
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Circadian clocks and insulin resistance
Stenvers, D. J., Scheer, F. A. J. L., Schrauwen, P., la Fleur, S. E., & Kalsbeek, A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0122-1 · Cited by 733 · see citing works
Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures
Potter, G. D., Skene, D. J., Arendt, J., Cade, J. E., Grant, P. J., & Hardie, L. J. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1083 · Cited by 729 · see citing works
Crosstalk between metabolism and circadian clocks
Reinke, H., & Asher, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0096-9 · Cited by 598 · see citing works
Meal timing regulates the human circadian system
Wehrens, S. M. T., Christou, S., Isherwood, C., Middleton, B., Gibbs, M. A., Archer, S. N., Skene, D. J., & Johnston, J. D. (2017) · Current Biology · doi:10.1016/j.cub.2017.04.059 · Cited by 596 · see citing works
Widespread seasonal gene expression reveals annual differences in human immunity and physiology
Dopico, X. C., Evangelou, M., Ferreira, R. C., Guo, H., Pękalski, M. Ł., Smyth, D. J., Cooper, N., Burren, O. S., Fulford, A. J. C., Hennig, B. J., et al. (2015) · Nature Communications · doi:10.1038/ncomms8000 · Cited by 539 · see citing works
Circadian clock genes and the transcriptional architecture of the clock mechanism
Cox, K. H., & Takahashi, J. S. (2019) · Journal of Molecular Endocrinology · doi:10.1530/jme-19-0153 · Cited by 481 · see citing works
Correa-de-Araujo, R., Addison, O., Miljkovic, I., Goodpaster, B. H., Bergman, B. C., Clark, R. V., Elena, J. W., Esser, K. A., Ferrucci, L., Harris-Love, M. O., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00963 · Cited by 468 · see citing works
Peek, C. B., Levine, D. C., Cedernaes, J., Taguchi, A., Kobayashi, Y., Tsai, S. J., Bonar, N. A., McNulty, M., Ramsey, K. M., & Bass, J. T. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.010 · Cited by 415 · see citing works
Circadian rhythms and exercise — re-setting the clock in metabolic disease
Gabriel, B. M., & Zierath, J. R. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0150-x · Cited by 382 · see citing works
Circadian System and Glucose Metabolism: Implications for Physiology and Disease
Qian, J., & Scheer, F. A. J. L. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.03.005 · Cited by 370 · see citing works
“In muscle-specific Bmal1 knockout mice, neither glucose tolerance nor insulin tolerance tests show any significant differences under chow-diet [39].”
BackgroundAtlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks
Dyar, K. A., Lutter, D., Artati, A., Ceglia, N., Liu, Y., Armenta, D., Jastroch, M., Schneider, S., de Mateo, S., Cervantes, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.042 · Cited by 335 · see citing works
Circadian control of glucose metabolism
Kalsbeek, A., la Fleur, S., & Fliers, E. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.03.002 · Cited by 338 · see citing works
“After submission of our manuscript we became aware of a recent study in which glucose metabolism was studied in a muscle-specific Bmal1 KO [153].”
MethodExercise Metabolism and Adaptation in Skeletal Muscle
Smith, J. A. B., Murach, K. A., Dyar, K. A., & Zierath, J. R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00606-x · Cited by 342 · see citing works
Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis
Sato, S., Basse, A. L., Schönke, M., Chen, S., Samad, M., Altıntaş, A., Laker, R. C., Dalbram, E., Barrès, R., Baldi, P., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.013 · Cited by 298 · see citing works
Endocrine Crosstalk Between Skeletal Muscle and the Brain
Delezie, J., & Handschin, C. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00698 · Cited by 270 · see citing works
“Second, these data imply a muscle-to-brain signaling involved in sleep regulation, either humoral, or, based on the observation that mice lacking Bmal1 in their muscles exhibit potent metabolic disruptions (152, 153), via metabolites.”
BackgroundExercise sustains the hallmarks of health
Qiu, Y., Fernández-García, B., Lehmann, H. I., Li, G., Kroemer, G., López-Otín, C., & Xiao, J. (2023) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2022.10.003 · Cited by 270 · see citing works
Circadian rhythms, metabolism, and chrononutrition in rodents and humans
Johnston, J. D., Ordovás, J. M., Scheer, F. A., & Turek, F. W. (2016) · Advances in Nutrition · doi:10.3945/an.115.010777 · Cited by 258 · see citing works
“For example, the hepatic clock regulates fasting glycemic control and glucose clearance (8), the pancreatic clock regulates insulin secretion and its response to glucose (9–11), the adipose clock regulates lipid storage and mobilization (12, 13), and the skeletal muscle clock regulates glucose uptake and metabolism (1…”
BackgroundHarfmann, B. D., Schroder, E. A., Kachman, M. T., Hodge, B. A., Zhang, X., & Esser, K. A. (2016) · Skeletal Muscle · doi:10.1186/s13395-016-0082-x · Cited by 231 · see citing works
The molecular athlete: exercise physiology from mechanisms to medals
Furrer, R., Hawley, J. A., & Handschin, C. (2023) · Physiological Reviews · doi:10.1152/physrev.00017.2022 · Cited by 232 · see citing works
Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity
van Moorsel, D., Hansen, J., Havekes, B., Scheer, F. A. J. L., Jörgensen, J. A., Hoeks, J., Schrauwen-Hinderling, V. B., Duez, H., Lefebvre, P., Schaper, N. C., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.012 · Cited by 218 · see citing works
Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism
Krishnaiah, S., Wu, G., Altman, B. J., Growe, J., Rhoades, S. D., Coldren, F., Venkataraman, A., Olarerin-George, A. O., Francey, L. J., Mukherjee, S., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.019 · Cited by 207 · see citing works
Circadian rhythms in mitochondrial respiration
de Goede, P., Wefers, J., Brombacher, E. C., Schrauwen, P., & Kalsbeek, A. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0196 · Cited by 211 · see citing works
“Disrupting the circadian clock by muscle-specific Bmal1 ablation resulted in a substantial decrease in 14C-glucose oxidation in isolated mouse diaphragms (Dyar et al. 2014).”
BackgroundCircadian Rhythms, the Molecular Clock, and Skeletal Muscle
Harfmann, B. D., Schroder, E. A., & Esser, K. A. (2015) · Journal of Biological Rhythms · doi:10.1177/0748730414561638 · Cited by 211 · see citing works
“Loss of the core clock gene Bmal1 results in severe muscle pathology, including fiber-type shifts, decreased mitochondria, impaired mitochondrial respiration, altered sarcomeric structure, and debilitated function (Andrews et al., 2010; Dyar et al., 2014).”
Circadian regulation of metabolism
Bailey, S. M., Udoh, U. S., & Young, M. E. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0200 · Cited by 211 · see citing works
Single muscle fiber proteomics reveals unexpected mitochondrial specialization
Murgia, M., Nagaraj, N., Deshmukh, A. S., Zeiler, M., Cancellara, P., Moretti, I., Reggiani, C., Schiaffino, S., & Mann, M. (2015) · EMBO Reports · doi:10.15252/embr.201439757 · Cited by 202 · see citing works
“Immunofluorescence with Myh isoform-specific antibodies was performed as described in [44].”
Circadian Etiology of Type 2 Diabetes Mellitus
Javeed, N., & Matveyenko, A. V. (2018) · Physiology · doi:10.1152/physiol.00003.2018 · Cited by 205 · see citing works
Wefers, J., van Moorsel, D., Hansen, J., Connell, N. J., Havekes, B., Hoeks, J., Lichtenbelt, W. D. V. M., Duez, H., Phielix, E., Kalsbeek, A., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1722295115 · Cited by 202 · see citing works
“In the control condition, the core clock genes BMAL1, CRY1, and PER2 displayed diurnal differences in mRNA expression levels, concordant with the results from our previous study (7) (Fig.”
BackgroundInfluentialCedernaes, J., Osler, M. E., Voisin, S., Broman, J.-E., Vogel, H., Dickson, S. L., Zierath, J. R., Schiöth, H. B., & Benedict, C. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2284 · Cited by 188 · see citing works
Nohara, K., Mallampalli, V. K. P. S., Nemkov, T. G., Wirianto, M., Yang, J., Ye, Y., Sun, Y., Han, L., Esser, K. A., Mileykovskaya, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11926-y · Cited by 190 · see citing works
Circadian regulation of lipid metabolism
Gooley, J. J. (2016) · Proceedings of The Nutrition Society · doi:10.1017/s0029665116000288 · Cited by 186 · see citing works
Circadian metabolism in the light of evolution
Gerhart-Hines, Z., & Lazar, M. A. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1007 · Cited by 178 · see citing works
Hodge, B. A., Wen, Y., Riley, L. A., Zhang, X., England, J. H., Harfmann, B. D., Schroder, E. A., & Esser, K. A. (2015) · Skeletal Muscle · doi:10.1186/s13395-015-0039-5 · Cited by 175 · see citing works
“observed similar expression patterns of Pdk4 and Pdp1 in skeletal muscle and were first to report a shift to carbohydrate utilization at the beginning of the active phase [43].”
InfluentialMechanisms of Communication in the Mammalian Circadian Timing System
Astiz, M., Heyde, I., & Oster, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020343 · Cited by 172 · see citing works
Misalignment with the external light environment drives metabolic and cardiac dysfunction
West, A. C., Smith, L. C., Ray, D. W., Loudon, A. S. I., Brown, T. M., & Bechtold, D. A. (2017) · Nature Communications · doi:10.1038/s41467-017-00462-2 · Cited by 168 · see citing works
Interconnections between circadian clocks and metabolism
Guan, D., & Lazar, M. A. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148278 · Cited by 166 · see citing works
Chrono-nutrition for the prevention and treatment of obesity and type 2 diabetes: from mice to men
Hawley, J. A., Sassone‐Corsi, P., & Zierath, J. R. (2020) · Diabetologia · doi:10.1007/s00125-020-05238-w · Cited by 155 · see citing works
Dyar, K. A., Hubert, M. J., Mir, A. A., Ciciliot, S., Lutter, D., Greulich, F., Quagliarini, F., Kleinert, M., Fischer, K., Eichmann, T. O., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005886 · Cited by 154 · see citing works
Jakubowicz, D., Wainstein, J., Ahrén, B., Bar-Dayan, Y., Landau, Z., Rabinovitz, H. R., & Froy, O. (2015) · Diabetologia · doi:10.1007/s00125-015-3524-9 · Cited by 139 · see citing works
Intrinsic muscle clock is necessary for musculoskeletal health
Schroder, E. A., Harfmann, B. D., Zhang, X., Srikuea, R., England, J. H., Hodge, B. A., Wen, Y., Riley, L. A., Yu, Q., Christie, A., et al. (2015) · The Journal of Physiology · doi:10.1113/jp271436 · Cited by 145 · see citing works
“The most recent research utilizing skeletal muscle-specific models of molecular clock disruption have focused on metabolic effects (Dyar et al. 2014; Hodge et al. 2015).”
BackgroundResultLananna, B. V., & Musiek, E. S. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104832 · Cited by 145 · see citing works
Off the Clock: From Circadian Disruption to Metabolic Disease
Maury, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071597 · Cited by 142 · see citing works
“Abrogation of the molecular clock restricted to adipose-tissue [116,117], pancreas [22,111], liver [113,118,119], skeletal muscle [120,121], smooth-muscle [122], myeloid cells [123,124] or even arcuate nucleus AgRP neurons [125] further confirmed this link (Figure 3).”
BackgroundTranscriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle
Perrin, L., Loizides-Mangold, U., Chanon, S., Gobet, C., Hulo, N., Isenegger, L., Weger, B. D., Migliavacca, E., Charpagne, A., Betts, J. A., et al. (2018) · eLife · doi:10.7554/elife.34114 · Cited by 139 · see citing works
“DOI: https://doi.org/10.7554/eLife.34114 16 of 30 shift in substrate utilization in skeletal muscle from carbohydrates to lipids with impact on muscle metabolism and glucose homeostasis (Dyar et al., 2014; Dyar et al., 2015; Hodge et al., 2015; Harfmann et al., 2016).”
BackgroundResultInfluentialFasting Imparts a Switch to Alternative Daily Pathways in Liver and Muscle
Kinouchi, K., Magnan, C., Ceglia, N., Liu, Y., Cervantes, M., Pastore, N., Huynh, T., Ballabio, A., Baldi, P., Masri, S., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.077 · Cited by 130 · see citing works
Cedernaes, J., Schönke, M., Westholm, J. O., Mi, J., Chibalin, A., Voisin, S., Osler, M., Vogel, H., Hörnaeus, K., Dickson, S. L., et al. (2018) · Science Advances · doi:10.1126/sciadv.aar8590 · Cited by 137 · see citing works
Ribas‐Latre, A., & Eckel‐Mahan, K. L. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2015.12.006 · Cited by 133 · see citing works
“134 MOLECULAR METABOLISM 5 (2016) 133e152 Published by Elsevier G that many metabolites involved in amino acid, carbohydrate, lipid, nucleotide and xenobiotic metabolic pathways, oscillate in liver [26], muscle [27] and plasma [28], whereas 15%e70% of the metabolome in humans exhibits circadian variation depending on…”
BackgroundBaHammam, A. S., & Pirzada, R. (2023) · Clocks & Sleep · doi:10.3390/clockssleep5030034 · Cited by 138 · see citing works
Metabolic rivalry: circadian homeostasis and tumorigenesis
Kinouchi, K., & Sassone‐Corsi, P. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0291-9 · Cited by 125 · see citing works
Greco, C. M., Koronowski, K. B., Smith, J. G., Shi, J., Kunderfranco, P., Carriero, R., Chen, S., Samad, M., Welz, P.-S., Zinna, V. M., et al. (2021) · Science Advances · doi:10.1126/sciadv.abi7828 · Cited by 124 · see citing works
Gabriel, B. M., Altıntaş, A., Smith, J. A. B., Puig, L. S., Zhang, X., Basse, A. L., Laker, R. C., Gao, H., Liu, Z., Dollet, L., et al. (2021) · Science Advances · doi:10.1126/sciadv.abi9654 · Cited by 118 · see citing works
Circadian Metabolism: From Mechanisms to Metabolomics and Medicine
Brown, S. A. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.03.015 · Cited by 118 · see citing works
Melatonin Signaling a Key Regulator of Glucose Homeostasis and Energy Metabolism
Owino, S., Buonfiglio, D. D. C., Tchio, C. I. M., & Tosini, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00488 · Cited by 124 · see citing works
Opperhuizen, A., Stenvers, D. J., Jansen, R., Foppen, E., Fliers, E., & Kalsbeek, A. (2017) · Diabetologia · doi:10.1007/s00125-017-4262-y · Cited by 114 · see citing works
CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity
Jordan, S. D., Kriebs, A., Vaughan, M. E., Duglan, D., Fan, W., Henriksson, E., Huber, A., Papp, S. J., Nguyen, M., Afetian, M. E., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.002 · Cited by 112 · see citing works
What time is it? Deep learning approaches for circadian rhythms
Agostinelli, F., Ceglia, N., Shahbaba, B., Sassone‐Corsi, P., & Baldi, P. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw243 · Cited by 107 · see citing works
Perrin, L., Loizides‐Mangold, U., Skarupelova, S., Pulimeno, P., Chanon, S., Robert, M., Bouzakri, K., Modoux, C., Roux‐Lombard, P., Vidal, H., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.07.009 · Cited by 105 · see citing works
Stenvers, D. J., Jongejan, A., Atiqi, S., Vreijling, J. P., Limonard, E. J., Endert, E., Baas, F., Moerland, P. D., Fliers, E., Kalsbeek, A., et al. (2019) · Diabetologia · doi:10.1007/s00125-019-4813-5 · Cited by 105 · see citing works
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Loizides‐Mangold, U., Perrin, L., Vandereycken, B., Betts, J. A., Walhin, J., Templeman, I., Chanon, S., Weger, B. D., Durand, C., Robert, M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705821114 · Cited by 104 · see citing works
“Recent data support a fundamental role for the circadian muscle clock in the regulation of glucose uptake, with a significant reduction in Glut4 mRNA and protein levels in two muscle specific Bmal1 knockout models (10, 11).”
BackgroundAoyama, S., & Shibata, S. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00063 · Cited by 106 · see citing works
“In addition, Dyar et al. showed that reductions in muscle weight and strength were not observed in inducible muscle-specific Bmal1 knockout mice once Bmal1 knockout was induced after development (Dyar et al., 2014).”
BackgroundMethodInfluentialZeitZeiger: supervised learning for high-dimensional data from an oscillatory system
Hughey, J., Hastie, T. J., & Butte, A. J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw030 · Cited by 103 · see citing works
Evidence for widespread dysregulation of circadian clock progression in human cancer
Shilts, J., Chen, G., & Hughey, J. (2018) · PeerJ · doi:10.7717/peerj.4327 · Cited by 99 · see citing works
Debattisti, V., Horn, A. J., Singh, R. P., Seifert, E. L., Hogarth, M. W., Mázala, D. A. G., Huang, K. T., Horváth, R., Jaiswal, J. K., & Hajnóczky, G. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.063 · Cited by 100 · see citing works
“Histology—Histology and fiber type staining were performed on TA sections as previously described (Dyar et al., 2013).”
MethodZhang, L., Xin, C., Wang, S., Zhuo, S., Zhu, J., Li, Z., Liu, Y., Yang, L., & Chen, Y. (2024) · Science Advances · doi:10.1126/sciadv.adn4508 · Cited by 103 · see citing works
“Fiber typing was performed with Development Studies Hybridoma Bank (DSHB) mouse monoclonal antibodies for MyHC I (BA-D5), MyHC IIA (SC71), and MyHC IIB (BF-F3), as previously described ( 47 ).”
MethodAt the Interface of Lifestyle, Behavior, and Circadian Rhythms: Metabolic Implications
Bae, S.-A., Fang, M., Rustgi, V. K., Zarbl, H., & Androulakis, I. P. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00132 · Cited by 100 · see citing works
“During the active phase, glucose is taken up by liver and muscle cells via insulin dependent transporters GLUT4 and GLUT2, which are partly regulated by the clock (88).”
BackgroundMuscle Directs Diurnal Energy Homeostasis through a Myokine-Dependent Hormone Module in Drosophila
Zhao, X. L., & Karpac, J. (2017) · Current Biology · doi:10.1016/j.cub.2017.06.004 · Cited by 98 · see citing works
“Lipid absorption, synthesis, and mobilization are also diurnally regulated in order to temporally coordinate energy homeostasis with changes in energy demands during rest-activity and feedingfasting cycles [8, 9], and muscle lipid consumption is thus under diurnal control [10, 11].”
Coupled network of the circadian clocks: a driving force of rhythmic physiology
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Metabolism and exercise: the skeletal muscle clock takes centre stage
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“For MHC isoforms composition, cryosections of gastrocnemius muscles were stained with monoclonal anti-MHC antibodies as described elsewhere.(35) All images were taken with Nikon Eclipse Ni confocal microscope and analysed with Nikon Elements C image acquisition software.”
MethodCircadian clock network desynchrony promotes weight gain and alters glucose homeostasis in mice
Kolbe, I., Leinweber, B., Brandenburger, M., & Oster, H. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.012 · Cited by 91 · see citing works
Time-of-Day-Dependent Physiological Responses to Meal and Exercise
Aoyama, S., & Shibata, S. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.00018 · Cited by 95 · see citing works
“or pancreatic βcell-specific clock gene mutant mice (30, 32, 33, 45, 46).”
BackgroundEffects of Intermittent Fasting on the Circulating Levels and Circadian Rhythms of Hormones
Kim, B. H., Joo, Y., Kim, M., Choe, H. K., Tong, Q., & Kwon, O. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.405 · Cited by 98 · see citing works
“For example, skeletal muscle-specific Bmal1 knockout mice showed impaired insulin-stimulated glucose uptake in skeletal muscle [37].”
BackgroundCLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice
Liu, J., Zhou, B. Z., Yan, M., Huang, R., Wang, Y., He, Z., Yang, Y., Dai, C., Wang, Y., Zhang, F., et al. (2016) · Endocrinology · doi:10.1210/en.2015-2027 · Cited by 89 · see citing works
The functional significance of the skeletal muscle clock: lessons from Bmal1 knockout models
Schiaffino, S., Blaauw, B., & Dyar, K. A. (2016) · Skeletal Muscle · doi:10.1186/s13395-016-0107-5 · Cited by 87 · see citing works
“Muscle histology and ultrastructure are normal, and muscle weight is even increased with a slight decrease in normalized muscle force [27].”
BackgroundResultInfluentialSleep, circadian rhythms, and type 2 diabetes mellitus
Parameswaran, G., & Ray, D. W. (2022) · Clinical Endocrinology · doi:10.1111/cen.14607 · Cited by 85 · see citing works
Endocrine regulation of circadian physiology
Tsang, A. H. K., Astiz, M., Friedrichs, M., & Oster, H. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0051 · Cited by 82 · see citing works
Coupling the Circadian Clock to Homeostasis: The Role of Period in Timing Physiology
Kim, P., Oster, H., Lehnert, H., Schmid, S. M., Salamat, N., Barclay, J. L., Maronde, E., Inder, W. J., & Rawashdeh, O. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00049 · Cited by 83 · see citing works
Time-of-Day Effects on Short-Duration Maximal Exercise Performance
Mirizio, G. G., Nunes, R. S. M., Vargas, D. A., Foster, C., & Vieira, E. C. (2020) · Scientific Reports · doi:10.1038/s41598-020-66342-w · Cited by 81 · see citing works
Time of Day and Muscle Strength: A Circadian Output?
Douglas, C. M., Hesketh, S. J., & Esser, K. A. (2020) · Physiology · doi:10.1152/physiol.00030.2020 · Cited by 80 · see citing works
Circadian regulation of metabolic homeostasis: causes and consequences
Young, M. E., & McGinnis, G. R. (2016) · Nature and Science of Sleep · doi:10.2147/nss.s78946 · Cited by 80 · see citing works
“133 In fact, muscle-specific Bmal1 −/− mice displayed reduced in vivo contractile force, while inducible Bmal1 −/− mice were similar to controls.”
A role for circadian clock in metabolic disease
Shimizu, I., Yoshida, Y., & Minamino, T. (2016) · Hypertension Research · doi:10.1038/hr.2016.12 · Cited by 79 · see citing works
Potential Roles of Dec and Bmal1 Genes in Interconnecting Circadian Clock and Energy Metabolism
Sato, F., Kohsaka, A., BHAWAL, U. K., & Muragaki, Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030781 · Cited by 78 · see citing works
“Insulin-dependent glucose uptake in skeletal muscle was also found to be associated with the function of the Bmal1 gene [53].”
BackgroundMcGinnis, G. R., Tang, Y., Brewer, R. A., Brahma, M. K., Stanley, H. L., Shanmugam, G., Rajasekaran, N. S., Rowe, G. C., Frank, S. J., Wende, A. R., et al. (2017) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2017.07.005 · Cited by 77 · see citing works
“(46) In addition to glucose catabolism, insulin promotes the channeling of glucose into glycogen, in part through Akt-dependent GSK3β phosphorylation/inactivation.”
BackgroundJakubowicz, D. J., Landau, Z., Tsameret, S., Wainstein, J., Raz, I., Åhrén, B., Chapnik, N., Barnea, M., Ganz, T., Menaged, M., et al. (2019) · Diabetes Care · doi:10.2337/dc19-1142 · Cited by 78 · see citing works
Dyar, K. A., Ciciliot, S., Tagliazucchi, G. M., Pallafacchina, G., Tothova, J., Argentini, C., Agatea, L., Abraham, R., Ahdesmaki, M. J., Forcato, M., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.09.004 · Cited by 75 · see citing works
Yoshino, J., Almeda-Valdes, P., Patterson, B. W., Okunade, A. L., Imai, S.-I., Mittendorfer, B., & Klein, S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1579 · Cited by 75 · see citing works
“However, the morning-to-evening direction of the variation in muscle clock gene expression in people is opposite from the direction observed in nocturnal mice (17, 19, 20).”
BackgroundSterling, P. (2020) · The MIT Press eBooks · doi:10.7551/mitpress/11472.001.0001 · Cited by 117 · see citing works
Abbondante, S., Eckel‐Mahan, K. L., Ceglia, N., Baldi, P., & Sassone‐Corsi, P. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.681130 · Cited by 69 · see citing works
Brain-muscle communication prevents muscle aging by maintaining daily physiology
Kumar, A., Vaca-Dempere, M., Mortimer, T., Deryagin, O., Smith, J. G., Petrus, P., Koronowski, K. B., Greco, C. M., Segalés, J., Andrés, E., et al. (2024) · Science · doi:10.1126/science.adj8533 · Cited by 70 · see citing works
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Immunometabolism around the Clock
Carroll, R. G., Timmons, G. A., Cervantes‐Silva, M. P., Kennedy, O. D., & Curtis, A. M. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.04.013 · Cited by 69 · see citing works
The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat
Stacpoole, P. W., & McCall, C. E. (2023) · Mitochondrion · doi:10.1016/j.mito.2023.02.007 · Cited by 68 · see citing works
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“are insulin resistant and have reduced protein levels of GLUT4[30], while liver specific deletion of Bmal1 leads to a stark increase in glucose tolerance[31].”
BackgroundInfluentialCircadian clock regulation of skeletal muscle growth and repair
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“The role of the endogenous skeletal muscle molecular clock in regulating muscle metabolic functions and whole body metabolic homeostasis has emerged recently 17,69,70 .”
BackgroundMitochondria and immunity in chronic fatigue syndrome
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Circadian Clocks Make Metabolism Run
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Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism
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“Skeletal muscle–specific Bmal1 ablation in mice results in decreased glucose uptake and oxidation, with increased Pdk4 expression causing a switch toward increased lipid metabolism in the muscles of these mice [41].”
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Glucose Homeostasis: Regulation by Peripheral Circadian Clocks in Rodents and Humans
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“Cellular proliferation is a critical event for the survival and restitution of tissues of all living things and the circadian system is capable of delivering temporary information to the cell cycle [102–104].”
Background
- Authors
- Dyar, K. A., Ciciliot, S., Wright, L. E., Biensø, R. S., Tagliazucchi, G. M., Patel, V. R., Forcato, M., Paz, M. I. P., Gudiksen, A., Solagna, F., Albiero, M., Moretti, I., Eckel-Mahan, K. L., Baldi, P., Sassone-Corsi, P., Rizzuto, R., Bicciato, S., Pilegaard, H., Blaauw, B., & Schiaffino, S.
- Affiliations
- Veneto Institute of Molecular Medicine (IT)
- University of Padua (IT)
- University of Copenhagen (DK)
- University of Modena and Reggio Emilia (IT)
- University of California, Irvine (US)
- Corresponding author
- Dyar, Kenneth A.
- Schiaffino, Stefano
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 3
- Issue
- 1
- Pages
- 29-41
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC3929910
- OpenAlex
- W1964634897
- Cited by
- 454
- References
- 73
- Citations by year
- 2026: 34 · 2025: 37 · 2024: 40 · 2023: 46 · 2022: 42 · 2021: 33 · 2020: 53 · 2019: 34 · 2018: 36 · 2017: 28 · 2016: 42 · 2015: 19 · 2014: 9 · 2013: 1
- FWCI
- 12.78
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-12-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by-nc-sa)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- European Commission (223576, 294777)
- Italian Space Agency (ASI, project OSMA)
- Italian Ministries of Health (Ricerca Finalizzata) and of Education, University and Research (PRIN, FIRB), NIA (2P01AG025532-06A1)
- Cariparo Foundation (Padua)
- Italian Association for Cancer Research (AIRC) and Telethon–Italy (GPP1005A, GGP11082)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- circadian rhythm, Bmal1, insulin sensitivity, glucose uptake, GLUT4, TBC1D1, pyruvate dehydrogenase, PDK4, PDP1, glucose oxidation, glycolysis, metabolome, conditional knockout mice
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