Circadian Clocks and Feeding Time Regulate the Oscillations and Levels of Hepatic Triglycerides
Open accessAbstract
Circadian clocks play a major role in orchestrating daily physiology, and their disruption can evoke metabolic diseases such as fatty liver and obesity. To study the role of circadian clocks in lipid homeostasis, we performed an extensive lipidomic analysis of liver tissues from wild-type and clock-disrupted mice either fed ad libitum or night fed. To our surprise, a similar fraction of lipids (∼17%) oscillated in both mouse strains, most notably triglycerides, but with completely different phases. Moreover, several master lipid regulators (e.g., PPARα) and enzymes involved in triglyceride metabolism retained their circadian expression in clock-disrupted mice. Nighttime restricted feeding shifted the phase of triglyceride accumulation and resulted in ∼50% decrease in hepatic triglyceride levels in wild-type mice. Our findings suggest that circadian clocks and feeding time dictate the phase and levels of hepatic triglyceride accumulation; however, oscillations in triglycerides can persist in the absence of a functional clock.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Circadian clocks play a major role in lipid homeostasis in humans and animals, particularly in relation to CVD but also nutrition and other body functions.
“As a result, mounting evidence now suggests that circadian clocks play a major role in lipid homeostasis both in humans and animals, particularly in relation to CVD but also nutrition and other body functions.”
From The Circadian Syndrome: is the Metabolic Syndrome and much more! (2019) · cites this paper as [69]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics
Matyash, V., Liebisch, G., Kurzchalia, T. V., Shevchenko, A., & Schwudke, D. (2008) · Journal of Lipid Research · doi:10.1194/jlr.d700041-jlr200 · Cited by 2,615 · see citing works
Obesity and Metabolic Syndrome in Circadian <i>Clock</i> Mutant Mice
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) · Science · doi:10.1126/science.1108750 · Cited by 2,485 · see citing works
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421 · see citing works
Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock
Panda, S., Antoch, M. P., Miller, B. H., Su, A. I., Schook, A. C., Straume, M., Schultz, P. G., Kay, S. A., Takahashi, J. S., & Hogenesch, J. B. (2002) · Cell · doi:10.1016/s0092-8674(02)00722-5 · Cited by 2,272 · see citing works
Preitner, N., Damiola, F., Luis-Lopez-Molina, Zakany, J., Duboule, D., Albrecht, U., & Schibler, U. (2002) · Cell · doi:10.1016/s0092-8674(02)00825-5 · Cited by 2,198 · see citing works
Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E. A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J. A. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.019 · Cited by 1,986 · see citing works
Extensive and divergent circadian gene expression in liver and heart
Storch, K.-F., Lipan, O., Leykin, I., Viswanathan, N., Davis, F. C., Wong, W. H., & Weitz, C. J. (2002) · Nature · doi:10.1038/nature744 · Cited by 1,509 · see citing works
Transcriptional architecture and chromatin landscape of the core circadian clock in mammals
Koike, N., Yoo, S.-H., Huang, H.-C., Kumar, V., Lee, C., Kim, T.-K., & Takahashi, J. S. (2012) · Science · doi:10.1126/science.1226339 · Cited by 1,464 · see citing works
mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway
Peterson, T. R., Sengupta, S., Harris, T. E., Carmack, A. E., Kang, S. A. W., Balderas, E., Guertin, D. A., Madden, K. L., Carpenter, A. E., Finck, B. N., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.034 · Cited by 1,233 · see citing works
Hughes, M. E., Hogenesch, J. B., & Kornacker, K. (2010) · Journal of Biological Rhythms · doi:10.1177/0748730410379711 · Cited by 1,087 · see citing works
Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β
Cho, H., Zhao, X., Hatori, M., Yu, R. T., Barish, G. D., Lam, M. T., Chong, L.-W., DiTacchio, L., Atkins, A. R., Glass, C. K., et al. (2012) · Nature · doi:10.1038/nature11048 · Cited by 1,037 · see citing works
Enzymes of triacylglycerol synthesis and their regulation
Coleman, R. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(03)00051-1 · Cited by 961 · see citing works
Nuclear Receptor Expression Links the Circadian Clock to Metabolism
Yang, X., Downes, M., Yu, R. T., Bookout, A. L., He, W., Straume, M., Mangelsdorf, D. J., & Evans, R. M. (2006) · Cell · doi:10.1016/j.cell.2006.06.050 · Cited by 934 · see citing works
Green, C. B., Takahashi, J. S., & Bass, J. (2008) · Cell · doi:10.1016/j.cell.2008.08.022 · Cited by 902 · see citing works
Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock.
Zheng, B., Albrecht, U., Kaasik, K., Sage, M., Lu, W., Vaishnav, S., Li, Q., Sun, Z. S., Eichele, G., Bradley, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00380-4 · Cited by 900 · see citing works
Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists
Solt, L. A., Wang, Y., Banerjee, S., Hughes, T., Kojetin, D. J., Lundåsen, T., Shin, Y., Liu, J., Cameron, M. D., Noël, R., et al. (2012) · Nature · doi:10.1038/nature11030 · Cited by 835 · see citing works
Akhtar, R. A., Reddy, A. B., Maywood, E. S., Clayton, J. D., King, V. M., Smith, A. G., Gant, T. W., Hastings, M. H., & Kyriacou, C. P. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00759-5 · Cited by 777 · see citing works
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Vollmers, C., Gill, S., DiTacchio, L., Pulivarthy, S. R., Le, H. D., & Panda, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909591106 · Cited by 765 · see citing works
Circadian topology of metabolism
Bass, J. T. (2012) · Nature · doi:10.1038/nature11704 · Cited by 610 · see citing works
Crosstalk 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 · see citing works
Self-citationThe human circadian metabolome
Dallmann, R., Viola, A. U., Tarokh, L., Cajochen, C., & Brown, S. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114410109 · Cited by 566 · see citing works
Han, X., Yang, K., & Gross, R. W. (2011) · Mass Spectrometry Reviews · doi:10.1002/mas.20342 · Cited by 530 · see citing works
Self-citationMetabolism and Circadian Rhythms—Implications for Obesity
Froy, O. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0014 · Cited by 505 · see citing works
Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic functionPreprint
Bugge, A. K., Feng, D., Everett, L. J., Briggs, E. R., Mullican, S. E., Wang, F., Jager, J., & Lazar, M. A. (2012) · Genes & Development · doi:10.1101/gad.186858.112 · Cited by 503 · see citing works
PER2 controls lipid metabolism by direct regulation of PPARγ
Grimaldi, B., Bellet, M. M., Katada, S., Astarita, G., Hirayama, J., Amin, R. H., Granneman, J. G., Piomelli, D., Leff, T., & Sassone-Corsi, P. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.10.005 · Cited by 489 · see citing works
Rey, G., Cesbron, F., Rougemont, J., Reinke, H., Brunner, M., & Naef, F. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000595 · Cited by 473 · see citing works
Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis
Takeuchi, K., & Reue, K. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90958.2008 · Cited by 463 · see citing works
REV-ERBα Participates in Circadian SREBP Signaling and Bile Acid Homeostasis
Martelot, G. L., Claudel, T., Gatfield, D., Schaad, O., Kornmann, B., Sasso, G. L., Moschetta, A., & Schibler, U. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000181 · Cited by 448 · see citing works
Yang, K., Cheng, H., Gross, R. W., & Han, X. (2009) · Analytical Chemistry · doi:10.1021/ac900241u · Cited by 416 · see citing works
Self-citationCoordination 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 · see citing works
Identification 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 · see citing works
Timed high-fat diet resets circadian metabolism and prevents obesity
Sherman, H., Genzer, Y., Cohen, R., Chapnik, N., Madar, Z., & Froy, O. (2012) · The FASEB Journal · doi:10.1096/fj.12-208868 · Cited by 360 · see citing works
Shimba, S., Ogawa, T., Hitosugi, S., Ichihashi, Y., Nakadaira, Y., Kobayashi, M., Tezuka, M., Kosuge, Y., Ishige, K., Ito, Y., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025231 · Cited by 347 · see citing works
Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding
Asher, G., Reinke, H., Altmeyer, M., Gutierrez-Arcelus, M., Hottiger, M. O., & Schibler, U. (2010) · Cell · doi:10.1016/j.cell.2010.08.016 · Cited by 340 · see citing works
Self-citationClocks, metabolism, and the epigenome
Feng, D., & Lazar, M. A. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.026 · Cited by 271 · see citing works
Measurement of internal body time by blood metabolomics
Minami, Y., Kasukawa, T., Kakazu, Y., Iigo, M., Sugimoto, M., Ikeda, S., Yasui, A., van der Horst, G. T. J., Soga, T., & Ueda, H. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900617106 · Cited by 261 · see citing works
Harris, T. E., Huffman, T. A., Chi, A., Shabanowitz, J., Hunt, D. F., Kumar, A. T., & Lawrence, J. C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609537200 · Cited by 211 · see citing works
Human blood metabolite timetable indicates internal body time
Kasukawa, T., Sugimoto, M., Hida, A., Minami, Y., Mori, M., Honma, S., Honma, K.-I., Mishima, K., Soga, T., & Ueda, H. R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207768109 · Cited by 211 · see citing works
Han, X., Yang, K., & Gross, R. W. (2008) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.3595 · Cited by 190 · see citing works
Self-citation(Re)inventing the Circadian Feedback Loop
Brown, S. A., Kowalska, E., & Dallmann, R. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.02.007 · Cited by 188 · see citing works
Role of Prescription Omega‐3 Fatty Acids in the Treatment of Hypertriglyceridemia
McKenney, J. M., & Sica, D. A. (2007) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.27.5.715 · Cited by 131 · see citing works
Quiroga, A. D., & Lehner, R. S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.09.007 · Cited by 77 · see citing works
Clock genes, intestinal transport and plasma lipid homeostasis
Hussain, M. M., & Pan, X. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.01.001 · Cited by 77 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis
Thaiss, C. A., Zeevi, D., Levy, M., Zilberman-Schapira, G., Suez, J., Tengeler, A. C., Abramson, L., Katz, M. N., Korem, T., Zmora, N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.048 · Cited by 1,449 · see citing works
Circadian physiology of metabolism
Panda, S. (2016) · Science · doi:10.1126/science.aah4967 · Cited by 1,092 · see citing works
Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan
Longo, V. D., & Panda, S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.001 · Cited by 1,013 · see citing works
Chaix, A., Zarrinpar, A., Miu, P., & Panda, S. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.11.001 · Cited by 956 · see citing works
Gill, S., & Panda, S. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.005 · Cited by 894 · see citing works
Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations
Thaiss, C. A., Levy, M., Korem, T., Dohnalová, L., Shapiro, H., Jaitin, D. A., David, E., Winter, D. R., Gury-BenAri, M., Tatirovsky, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.003 · Cited by 870 · see citing works
Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock
Asher, G., & Sassone-Corsi, P. (2015) · Cell · doi:10.1016/j.cell.2015.03.015 · Cited by 844 · see citing works
Self-citationCrosstalk 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
Self-citationThe circadian regulation of food intake
Challet, E. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0210-x · Cited by 428 · see citing works
The Circadian Syndrome: is the Metabolic Syndrome and much more!
Zimmet, P., Alberti, K. G. M. M., Stern, N., Bilu, C., El‐Osta, A., Einat, H., & Kronfeld‐Schor, N. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12924 · Cited by 387 · see citing works
Circadian Clock Control of Liver Metabolic Functions
Reinke, H., & Asher, G. (2016) · Gastroenterology · doi:10.1053/j.gastro.2015.11.043 · Cited by 321 · see citing works
Self-citationDaily eating patterns and their impact on health and disease
Zarrinpar, A., Chaix, A., & Panda, S. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.11.007 · Cited by 263 · see citing works
Neufeld-Cohen, A., Robles, M. S., Aviram, R., Manella, G., Adamovich, Y., Ladeuix, B., Nir, D., Rousso-Noori, L., Kuperman, Y., Golik, M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1519650113 · Cited by 262 · see citing works
Self-citationCircadian timing of metabolism in animal models and humans
Dibner, C., & Schibler, U. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12347 · Cited by 237 · see citing works
Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals
Kumar Jha, P., Challet, E., & Kalsbeek, A. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.01.024 · Cited by 235 · see citing works
Papakonstantinou, E., Oikonomou, C., Nychas, G., & Dimitriadis, G. D. (2022) · Nutrients · doi:10.3390/nu14040823 · Cited by 199 · see citing works
Time‐restricted feeding for prevention and treatment of cardiometabolic disorders
Melkani, G. C., & Panda, S. (2017) · The Journal of Physiology · doi:10.1113/jp273094 · Cited by 155 · see citing works
Transcriptomic 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
Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism
Gnocchi, D., Pedrelli, M., Hurt-Camejo, E., & Parini, P. (2015) · Biology · doi:10.3390/biology4010104 · Cited by 115 · see citing works
Mindikoglu, A. L., Opekun, A. R., Gagan, S. K., & Devaraj, S. (2017) · Gastroenterology Research and Practice · doi:10.1155/2017/3932491 · Cited by 49 · see citing works
Luu, H. N., Behari, J., Goh, G. B.-B., Wang, R., Jin, A., Thomas, C. E., Clemente, J. C., Odegaard, A. O., Koh, W.-P., & Yuan, J.-M. (2021) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-20-1201 · Cited by 33 · see citing works
The Liver in the Eyes of a Chronobiologist
Zwighaft, Z., Reinke, H., & Asher, G. (2016) · Journal of Biological Rhythms · doi:10.1177/0748730416633552 · Cited by 29 · see citing works
Self-citationHarfmann, B. D., Schroder, E. A., England, J. H., Senn, N. J., Westgate, P. M., Esser, K. A., & Kern, P. A. (2017) · Journal of the Endocrine Society · doi:10.1210/js.2017-00086 · Cited by 16 · see citing works
- Authors
- Adamovich, Y., Rousso-Noori, L., Zwighaft, Z., Neufeld-Cohen, A., Golik, M., Kraut-Cohen, J., Wang, M., Han, X., & Asher, G.
- Affiliations
- Weizmann Institute of Science (IL)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Asher, Gad
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 19
- Issue
- 2
- Pages
- 319-330
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4261230
- OpenAlex
- W2080019362
- Cited by
- 410
- References
- 43
- Citations by year
- 2026: 19 · 2025: 34 · 2024: 32 · 2023: 32 · 2022: 38 · 2021: 47 · 2020: 45 · 2019: 36 · 2018: 30 · 2017: 28 · 2016: 30 · 2015: 26 · 2014: 10 · 2012: 1
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG031675, R01AG-31675)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- circadian clock, hepatic triglycerides, meal timing, nocturnal feeding, lipidomics, PPARα, triglyceride metabolism, lipid homeostasis, hepatic steatosis, obesity
- MeSH terms
- Animals, Liver, Male, Models, Biological, Triglycerides, Mice, Circadian Clocks, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
