AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Open accessAbstract
AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio. Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin, thiazolidinediones and exercise, which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP. This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD+-dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-gamma coactivator 1alpha and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.
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Mitochondrial synthesis in myocytes is upregulated to meet the demands of increased capillary density, leading to greater oxygen extraction and metabolism through calcium and metabolic signalling pathways such as AMPK and sirtuins.
“The synthesis of mitochondria in myocytes is upregulated to meet the demands associated with an increase in capillary density, which in turn leads to increased oxygen extraction and metabolism122 through the induction of calcium and metabolic signalling pathways such as those involving 5’-AMP-activated serine/threonine-protein kinase (AMPK) and sirtuins123.”
From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [123]
The passages labelled Abstract (page unavailable) link AMPK and SIRT1 activity to mitochondrial gene expression and oxygen consumption in myotubes and skeletal muscle. They do not establish calcium signalling or say that increased capillary density drives mitochondrial synthesis; the paper measures cellular oxygen consumption, not oxygen extraction associated with capillary density. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSIRT1 increases mitochondrial activity and biogenesis by deacetylating and activating PGC1α.
“SIRT1 increases mitochondrial activity and biogenesis by deacetylating and activating PGC1α (peroxisome proliferator-activated receptor-γ co-activator 1α) [102].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [102]
The paper’s main text (indexed under Abstract; page unavailable) shows that SIRT1-mediated deacetylation activates PGC-1α and helps mediate AMPK-induced mitochondrial gene expression and oxygen consumption. It does not establish an increase in mitochondrial biogenesis itself, and its findings concern SIRT1’s role in the response to AMPK activation rather than an unqualified effect of SIRT1. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAMPK senses changes in intracellular AMP/ATP ratio; during energy limitation, low ATP activates AMPK to maintain cellular energy stores.
“The adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy regulator which senses changes in the intracellular AMP/ATP ratio. During energy limitation, low levels of ATP activate AMPK, which acts to maintain cellular energy stores.”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [102]
AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in deacetylation and modulation of energy metabolism-related downstream SIRT1 targets including PGC1α, FOXO1, and FOXO3a.
“Thus, AMPK enhances the SIRT1 activity by increasing cellular NAD+ levels, resulting in the deacetylation and modulation of the activity of energy metabolism-related downstream SIRT1 targets, which include the PGC1α, the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors [102].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [102]
In mammalian systems, lifespan-extending metabolic manipulations such as exercise, caloric restriction, time-restricted feeding, a ketogenic diet, and healthy circadian rhythms work in part by increasing NAD+ levels, which leads to activation of sirtuins.
“In support of this hypothesis, it has now been demonstrated in mammalian systems that lifespan-extending metabolic manipulations, such as exercise75–77, caloric restriction78, time-restricted feeding and a ketogenic diet79, as well as healthy circadian rhythms1,11 (including regular sleep patterns80), work in part by increasing NAD+ levels, which leads to the activation of sirtuins.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [77]
SIRT1 is activated in response to metabolic changes, such as low glucose or exercise, that increase cellular NAD+.
“SIRT1 is known to be activated in response to metabolic changes, such as low glucose or exercise, that increase cellular NAD+ (62, 354).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [62]
Drug-induced activation of AMPK produces gene expression patterns similar to those observed during exercise.
“Drug-induced activation of AMPK produces gene expression patterns similar to those observed during exercise (104).”
From Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility (2024) · cites this paper as [104]
SIRT1 deacetylation of FOXO1 and FOXO3a mediates autophagic signaling in muscle cells, and aging attenuates SIRT1, reducing autophagy.
“Deacetylation of FOXO1 and FOXO3a by SIRT1 (19, 20) mediates autophagic signaling in muscle cells, and aging attenuates SIRT1, which reduces autophagy (134).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [19]
AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in deacetylation and modulation of downstream SIRT1 targets.
“Recent studies show that AMPK also enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets 160.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [160]
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Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290 · see citing works
Self-citationLagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Self-citationTranscriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · see citing works
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239 · see citing works
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160 · see citing works
Self-citationAMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · see citing works
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., et al. (2006) · Nature · doi:10.1038/nature04330 · Cited by 2,220 · see citing works
Self-citationAMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,207 · see citing works
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950 · see citing works
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B., et al. (2007) · Nature · doi:10.1038/nature06261 · Cited by 1,707 · see citing works
Self-citationMetabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC‐1α
Gerhart‐Hines, Z., Rodgers, J. T., Bare, O., Lerin, C., Kim, S., Mostoslavsky, R., Alt, F. W., Wu, Z., & Puigserver, P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601633 · Cited by 1,294 · see citing works
Self-citationSIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
Nemoto, S., Fergusson, M. M., & Finkel, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501485200 · Cited by 1,047 · see citing works
Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252625599 · Cited by 1,036 · see citing works
Fryer, L. G. D., Patel, A. P., & Carling, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202489200 · Cited by 1,030 · see citing works
Revollo, J. R., Grimm, A. A., & Imai, S.-I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408388200 · Cited by 1,010 · see citing works
Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205670200 · Cited by 1,002 · see citing works
Cool, B. L., Zinker, B. A., Chiou, W. J. H., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A. L., Gagné, G. D., Iyengar, R., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.005 · Cited by 932 · see citing works
Fulco, M., Cen, Y., Zhao, P., Hoffman, E. P., McBurney, M. W., Sauve, A. A., & Sartorelli, V. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.004 · Cited by 821 · see citing works
Greer, E. L., Oskoui, P. R., Banko, M. R., Maniar, J. M., Gygi, M. P., Gygi, S. P., & Brunet, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705325200 · Cited by 820 · see citing works
Handschin, C., Rhee, J., Lin, J., Tarr, P. T., & Spiegelman, B. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1232352100 · Cited by 729 · see citing works
Resveratrol stimulates AMP kinase activity in neurons
Dasgupta, B., & Milbrandt, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610068104 · Cited by 723 · see citing works
Feige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.017 · Cited by 719 · see citing works
Self-citationHasmann, M., & Schemainda, I. (2003) · PubMed · Cited by 618 · see citing works
Huss, J. M., Kopp, R. P., & Kelly, D. P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206324200 · Cited by 480 · see citing works
Pich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., & Zorzano, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi149 · Cited by 455 · see citing works
Hayashi, T., Hirshman, M. F., Fujii, N., Habinowski, S. A., Witters, L. A., & Goodyear, L. J. (2000) · Diabetes · doi:10.2337/diabetes.49.4.527 · Cited by 447 · see citing works
Woods, A., Azzout‐Marniche, D., Foretz, M., STEIN, S. C., Lemarchand, P., Ferré, P., Foufelle, F., & Carling, D. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.18.6704-6711.2000 · Cited by 404 · see citing works
Wende, A. R., Huss, J. M., Schaeffer, P. J., Giguère, V., & Kelly, D. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10684-10694.2005 · Cited by 354 · see citing works
Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress
Chua, K. F., Mostoslavsky, R., Lombard, D. B., Pang, W. W., Saito, S., Franco, S., Kaushal, D., Cheng, H.-L., Fischer, M. R., Stokes, N., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.06.007 · Cited by 257 · see citing works
Suwa, M., Nakano, H., & Kumagai, S. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00349.2003 · Cited by 250 · see citing works
Lin, S., Manchester, J. K., & Gordon, J. I. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103509200 · Cited by 188 · see citing works
Barnes, B. R., Long, Y. C., Steiler, T. L., Leng, Y., Galuska, D., Wojtaszewski, J. F. P., Andersson, L., & Zierath, J. R. (2005) · Diabetes · doi:10.2337/diabetes.54.12.3484 · Cited by 60 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- [1]Rodgers JT Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1 Nature 2005 434 113 8 15744310
- [3]Wende AR Huss JM Schaeffer PJ Giguere V Kelly DP PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolism Mol Cell Biol 2005 25 10684 94 16314495 PMC1316952
- [4]Huss JM Kopp RP Kelly DP Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha J Biol Chem 2002 277 40265 74 12181319
- [5]Jager S Handschin C St-Pierre J Spiegelman BM AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha Proc Natl Acad Sci U S A 2007 104 12017 22 17609368 PMC1924552
- [6]Lagouge M Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha Cell 2006 127 1109 22 17112576
- [9]Milne JC Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes Nature 2007 450 712 6 18046409 PMC2753457
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Price, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.003 · Cited by 1,602 · see citing works
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482 · see citing works
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Luen Tang, B. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2318 · Cited by 740 · see citing works
Targeting inflammation in the treatment of type 2 diabetes: time to start
Donath, M. Y. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4275 · Cited by 690 · see citing works
Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
Verdin, E., Hirschey, M. D., Finley, L. W. S., & Haigis, M. C. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.003 · Cited by 661 · see citing works
AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Um, J.-H., Park, S.-J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., & Chung, J. H. (2010) · Diabetes · doi:10.2337/db09-0482 · Cited by 647 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Self-citationSirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Herranz, D., Muñoz-Martin, M., Cañamero, M., Mulero, F., Martinez-Pastor, B., Fernandez-Capetillo, O., & Serrano, M. (2010) · Nature Communications · doi:10.1038/ncomms1001 · Cited by 612 · 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
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
Cellular bioenergetics as a target for obesity therapy
Tseng, Y.-H., Cypess, A. M., & Kahn, C. R. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3138 · Cited by 591 · see citing works
The metabolic footprint of aging in mice
Houtkooper, R. H., Argmann, C., Houten, S. M., Cantó, C., Jeninga, E. H., Andreux, P. A., Thomas, C., Doenlen, R., Schoonjans, K., & Auwerx, J. (2011) · Scientific Reports · doi:10.1038/srep00134 · Cited by 528 · see citing works
Self-citationLkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells
Nakada, D., Saunders, T. L., & Morrison, S. J. (2010) · Nature · doi:10.1038/nature09571 · Cited by 524 · see citing works
A two-way street: reciprocal regulation of metabolism and signalling
Wellen, K. E., & Thompson, C. B. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3305 · Cited by 528 · see citing works
Health benefits of resveratrol: Evidence from clinical studies
Singh, A. P., Singh, R., Verma, S. S., Rai, V., Kaschula, C. H., Maiti, P., & Gupta, S. C. (2019) · Medicinal Research Reviews · doi:10.1002/med.21565 · Cited by 523 · see citing works
Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496 · see citing works
“Increasing SIRT1 activity has been thought to improve endurance capacity by increasing mitochondrial function (Bai et al., 2011a, 2011b; Baur et al., 2006; Cantó et al., 2009; Lagouge et al., 2006; Pearson et al., 2008).”
Guarente, L. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1100831 · Cited by 510 · see citing works
Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake
Merz, K. E., & Thurmond, D. C. (2020) · Comprehensive Physiology · doi:10.1002/cphy.c190029 · Cited by 494 · see citing works
NAD(+) in aging: molecular mechanisms and translational implications
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.001 · Cited by 501 · see citing works
AMPK at the Nexus of Energetics and Aging
Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483 · see citing works
Metabolism and Circadian Rhythms—Implications for Obesity
Froy, O. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0014 · Cited by 505 · see citing works
Redox regulation of SIRT1 in inflammation and cellular senescence
Hwang, J.-W., Yao, H., Caito, S., Sundar, I. K., & Rahman, I. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.015 · Cited by 503 · see citing works
Regulation of autophagy by cytosolic acetyl-coenzyme A
Mariño, G., Pietrocola, F., Eisenberg, T., Kong, Y., Malik, S. A., Andryushkova, A., Schroeder, S., Pendl, T., Harger, A., Niso-Santano, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.01.016 · Cited by 500 · see citing works
Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1α in skeletal muscle
Palacios, O. M., Carmona, J. J., Michan, S., Chen, K. Y., Manabe, Y., III, J. L. W., Goodyear, L. J., & Tong, Q. (2009) · Aging · doi:10.18632/aging.100075 · Cited by 487 · see citing works
Mitochondrial biogenesis and dynamics in the developing and diseased heart
Dorn, G. W., Vega, R. B., & Kelly, D. P. (2015) · Genes & Development · doi:10.1101/gad.269894.115 · Cited by 470 · see citing works
The molecular targets of resveratrol
Kulkarni, S. S., & Cantó, C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.10.005 · Cited by 477 · see citing works
“This increase in NAD availability might derive from, at least, two complementary actions: on one hand, the increase in fat oxidation rates induced by AMPK would be permissive for an increase in NAD within hours after treatment [78].”
BackgroundInfluentialSelf-citationSirtuins, a promising target in slowing down the ageing process
Grabowska, W., Sikora, E., & Bielak-Zmijewska, A. (2017) · Biogerontology · doi:10.1007/s10522-017-9685-9 · Cited by 470 · see citing works
Calorie restriction and sirtuins revisited
Guarente, L. (2013) · Genes & Development · doi:10.1101/gad.227439.113 · Cited by 464 · see citing works
Prasanth, M. I., Sivamaruthi, B. S., Chaiyasut, C., & Tencomnao, T. (2019) · Nutrients · doi:10.3390/nu11020474 · Cited by 457 · see citing works
Mitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434 · see citing works
Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
Cantó, C., & Auwerx, J. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003905 · Cited by 433 · see citing works
Self-citationResveratrol is not a direct activator of SIRT1 enzyme activity
Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S., Atangan, L., & Wang, M. (2009) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2009.00901.x · Cited by 426 · see citing works
AMP-activated protein kinase and its downstream transcriptional pathways
Cantó, C., & Auwerx, J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0454-z · Cited by 421 · see citing works
Self-citationPGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity
Lira, V. A., Benton, C. R., Yan, Z., & Bonen, A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00755.2009 · Cited by 412 · see citing works
Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1
Gomes, B. A. Q., Silva, J. P. B., Romeiro, C. F. R., dos Santos, S. M., Rodrigues, C. A., Gonçalves, P. R., Sakai, J. T., Mendes, P. F. S., Varela, E. L. P., & Monteiro, M. C. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/8152373 · Cited by 403 · see citing works
O'Neill, H. M., Maarbjerg, S. J., Crane, J. D., Jeppesen, J., Jørgensen, S. B., Schertzer, J. D., Shyroka, O., Kiens, B., van Denderen, B. J., Tarnopolsky, M. A., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105062108 · Cited by 406 · see citing works
SIRT1 Negatively Regulates the Mammalian Target of Rapamycin
Ghosh, H. S., McBurney, M., & Robbins, P. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009199 · Cited by 397 · see citing works
Caloric restriction, SIRT1 and longevity
Cantó, C., & Auwerx, J. (2009) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.03.008 · Cited by 395 · see citing works
Self-citationDegradation of AMPK by a Cancer-Specific Ubiquitin Ligase
Pineda, C. T., Ramanathan, S., Fon Tacer, K., Weon, J. L., Potts, M. B., Ou, Y.-H., White, M. A., & Potts, P. R. (2015) · Cell · doi:10.1016/j.cell.2015.01.034 · Cited by 389 · see citing works
Nuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387 · see citing works
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
Khan, N. A., Auranen, M., Paetau, I., Pirinen, E., Euro, L., Forsström, S., Pasila, L., Velagapudi, V., Carroll, C. J., Auwerx, J., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201403943 · Cited by 385 · see citing works
Self-citationPharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383 · see citing works
Self-citationRedox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377 · see citing works
Sensing of energy and nutrients by AMP-activated protein kinase
Hardie, D. G. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001925 · Cited by 372 · see citing works
Li, X. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms108 · Cited by 360 · see citing works
Egan, B., Carson, B. P., Garcia-Roves, P. M., Chibalin, A. V., Sarsfield, F. M., Barron, N., McCaffrey, N., Moyna, N. M., Zierath, J. R., & O’Gorman, D. J. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.188011 · Cited by 373 · see citing works
Mitophagy in neurodegeneration and aging
Fivenson, E. M., Lautrup, S., Sun, N., Scheibye-Knudsen, M., Stevnsner, T., Nilsen, H., Bohr, V. A., & Fang, E. F. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.02.007 · Cited by 364 · see citing works
AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity.
O’Neill, H. M., Holloway, G. P., & Steinberg, G. R. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.06.019 · Cited by 364 · see citing works
The AMPK pathway in fatty liver disease
Fang, C., Pan, J., Qu, N., Lei, Y., Han, J., Zhang, J., & Han, D. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.970292 · Cited by 364 · see citing works
Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?
Tak, Y. J., & Lee, S. Y. (2021) · Current Obesity Reports · doi:10.1007/s13679-020-00422-w · Cited by 343 · see citing works
Little, J. P., Safdar, A., Bishop, D., Tarnopolsky, M. A., & Gibala, M. J. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00538.2010 · Cited by 342 · see citing works
Repairing mitochondrial dysfunction in disease
Sorrentino, V., Menzies, K. J., & Auwerx, J. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104908 · Cited by 337 · see citing works
Protein acetylation in metabolism – metabolites and cofactors
Menzies, K. J., Zhang, H., Katsyuba, E., & Auwerx, J. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.181 · Cited by 331 · see citing works
Self-citationMitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
Calvani, R., Joseph, A.-M., Adhihetty, P. J., Miccheli, A., Bossola, M., Leeuwenburgh, C., Bernabei, R., & Marzetti, E. (2013) · bchm · doi:10.1515/hsz-2012-0247 · Cited by 328 · see citing works
Unraveling the regulation of hepatic gluconeogenesis
Zhang, X., Yang, S., Chen, J., & Su, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00802 · Cited by 314 · see citing works
Of mice and men: the benefits of caloric restriction, exercise, and mimetics
Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.11.005 · Cited by 318 · see citing works
Zu, Y., Liu, L., Lee, M. Y. K., Xu, C., Liang, Y., Man, R. Y., Vanhoutte, P. M., & Wang, Y. (2010) · Circulation Research · doi:10.1161/circresaha.109.215483 · Cited by 303 · see citing works
Han, X., Tai, H., Wang, X., Wang, Z., Zhou, J., Wei, X., Ding, Y., Gong, H., Mo, C., Zhang, J., et al. (2016) · Aging Cell · doi:10.1111/acel.12446 · Cited by 302 · see citing works
Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3
Lee, J. H., Budanov, A. V., Talukdar, S., Park, E. J., Park, H. L., Park, H.-W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.004 · Cited by 295 · see citing works
Long, J.-K., Dai, W., Zheng, Y.-W., & Zhao, S.-P. (2019) · Molecular Medicine · doi:10.1186/s10020-019-0085-2 · Cited by 281 · see citing works
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
Zheng, Z., Chen, H., Li, J., Li, T., Zheng, B., Zheng, Y., Jin, H., He, Y., Gu, Q., & Xu, X. (2012) · Diabetes · doi:10.2337/db11-0416 · Cited by 282 · see citing works
Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats
Koltai, E., Szabo, Z., Atalay, M., Boldogh, I., Naito, H., Goto, S., Nyakas, C., & Radak, Z. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.11.002 · Cited by 283 · see citing works
- Authors
- Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- Corresponding author
- Auwerx, Johan
- Venue
- Nature
- Published
- 2009-03-04
- Volume
- 458
- Issue
- 7241
- Pages
- 1056-1060
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3616311
- OpenAlex
- W2022267544
- Cited by
- 3,300
- References
- 33
- Citations by year
- 2026: 197 · 2025: 185 · 2024: 185 · 2023: 191 · 2022: 221 · 2021: 221 · 2020: 231 · 2019: 191 · 2018: 195 · 2017: 187 · 2016: 206 · 2015: 175 · 2014: 179 · 2013: 200 · 2012: 183
- FWCI
- 71.47
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-59820, DK069966, R01DK069966, P01DK059820)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- AMPK, SIRT1, NAD+ metabolism, energy expenditure, skeletal muscle, PGC-1α, FOXO1, FOXO3, deacetylation, mitochondrial biogenesis, oxidative metabolism, type 2 diabetes, transcriptional regulation
- MeSH terms
- Forkhead Box Protein O1, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Forkhead Box Protein O3, Acetylation, Aminoimidazole Carboxamide, Animals, Cell Line, Energy Metabolism, Enzyme Activation, Gene Expression Regulation, Male, Mutation, NAD, Oxygen Consumption, Phosphorylation, Ribonucleotides, Transcription Factors, Transcription, Genetic, Trans-Activators, Muscle, Skeletal, Sirtuins, Genes, Mitochondrial, Mice, Forkhead Transcription Factors, AMP-Activated Protein Kinases, Sirtuin 1
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