Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation
Open accessAbstract
Sirt3 is an NAD+-dependent deacetylase that regulates mitochondrial function by targeting metabolic enzymes and proteins. In fasting mice, Sirt3 expression is decreased in skeletal muscle resulting in increased mitochondrial protein acetylation. Deletion of Sirt3 led to impaired glucose oxidation in muscle, which was associated with decreased pyruvate dehydrogenase (PDH) activity, accumulation of pyruvate and lactate metabolites, and an inability of insulin to suppress fatty acid oxidation. Antibody-based acetyl-peptide enrichment and mass spectrometry of mitochondrial lysates from WT and Sirt3 KO skeletal muscle revealed that a major target of Sirt3 deacetylation is the E1α subunit of PDH (PDH E1α). Sirt3 knockout in vivo and Sirt3 knockdown in myoblasts in vitro induced hyperacetylation of the PDH E1α subunit, altering its phosphorylation leading to suppressed PDH enzymatic activity. The inhibition of PDH activity resulting from reduced levels of Sirt3 induces a switch of skeletal muscle substrate utilization from carbohydrate oxidation toward lactate production and fatty acid utilization even in the fed state, contributing to a loss of metabolic flexibility. Thus, Sirt3 plays an important role in skeletal muscle mitochondrial substrate choice and metabolic flexibility in part by regulating PDH function through deacetylation.
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SIRT3 plays an important role in regulating metabolic flexibility of muscle.
“SIRT3 recently has been reported to play an important role in regulating metabolic flexibility of muscle (31) as well as regulating muscle mass and OXPHOS (32).”
From Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age (2015) · cites this paper as [31]
SIRT3 plays an important role in regulating muscle mass and OXPHOS.
“SIRT3 recently has been reported to play an important role in regulating metabolic flexibility of muscle (31) as well as regulating muscle mass and OXPHOS (32).”
From Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age (2015) · cites this paper as [31]
Prolonged hypernutrition leads to type 2 diabetes and impairs skeletal muscle glucose uptake.
“However, prolonged hypernutrition leads to type 2 diabetes, and has been shown to impair skeletal muscle glucose uptake in a manner exacerbated by the loss of SIRT3 (Jing et al. 2013),(Lantier et al. 2015).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Jing et al. 2013
Loss of SIRT3 exacerbates hypernutrition-induced impairment of skeletal muscle glucose uptake.
“However, prolonged hypernutrition leads to type 2 diabetes, and has been shown to impair skeletal muscle glucose uptake in a manner exacerbated by the loss of SIRT3 (Jing et al. 2013),(Lantier et al. 2015).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Jing et al. 2013
Acetylation of PDHA1 K321 recruits PDK, leading to PDC phosphorylation and inhibition of its enzymatic activity.
“Acetylation of PDHA1 K321 recruits PDK leading to PDC phosphorylation and inhibition of its enzymatic activity.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Jing et al. 2013
A functional role for acetylation has only been demonstrated for modification of PDHA1 lysine 321.
“Lysine acetylation has been observed on DLD and PDHA1 at multiple residues ((Rardin, Newman, et al. 2013)), but a functional role for acetylation has only been demonstrated for modification of lysine 321 of PDHA1 ((Jing et al. 2013)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Jing et al. 2013
SIRT3 knockout mice exhibit metabolic changes similar to those observed in human metabolic syndrome.
“SIRT3 knockout mice exhibit metabolic changes similar to those observed in the human metabolic syndrome ((Hirschey et al. 2011);(Jing et al. 2013)), and a human SIRT3 polymorphism associated with reduced SIRT3 deacetylase activity is associated with increased risk of metabolic syndrome in humans ((Hirschey et al. 2011).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Jing et al. 2013
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Cites
Lysine acetylation targets protein complexes and co-regulates major cellular functions
Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009) · Science · doi:10.1126/science.1175371 · Cited by 4,040 · see citing works
Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes
DeFronzo, R. A., & Tripathy, D. (2009) · Diabetes Care · doi:10.2337/dc09-s302 · Cited by 2,102 · cited 1× · see citing works
“In both insulin resistance and type 2 diabetes, this metabolic flexibility is compromised in that skeletal muscle fails to switch substrate utilization from lipid metabolism to insulin-stimulated glucose oxidation (5,48).”
BackgroundRegulation of cellular metabolism by protein lysine acetylation
Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., et al. (2010) · Science · doi:10.1126/science.1179689 · Cited by 1,910 · see citing works
Sirtuins in mammals: insights into their biological function
Michán, S., & Sinclair, D. A. (2007) · Biochemical Journal · doi:10.1042/bj20070140 · Cited by 1,719 · see citing works
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., et al. (2010) · Nature · doi:10.1038/nature08778 · Cited by 1,687 · see citing works
Self-citationCalorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation
Qiu, X., Brown, K., Hirschey, M. D., Verdin, E., & Chen, D. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.015 · Cited by 1,310 · see citing works
Self-citationA role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis
Ahn, B.-H., Kim, H.-S., Song, S., Lee, I. H., Liu, J., Vassilopoulos, A., Deng, C.-X., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803790105 · Cited by 1,291 · see citing works
Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
Lombard, D. B., Alt, F. W., Cheng, H.-L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01636-07 · Cited by 1,216 · see citing works
Self-citationOrganelle isolation: functional mitochondria from mouse liver, muscle and cultured filroblasts
Frezza, C., Cipolat, S., & Scorrano, L. (2007) · Nature Protocols · doi:10.1038/nprot.2006.478 · Cited by 1,188 · see citing works
Leone, T. C., Lehman, J. J., Finck, B. N., Schaeffer, P. J., Wende, A. R., Boudina, S., Courtois, M., Wozniak, D. F., Sambandam, N., Bernal-Mizrachi, C., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030101 · Cited by 951 · see citing works
Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival
Yang, H., Yang, T., Baur, J. A., Perez, E., Matsui, T., Carmona, J. J., Lamming, D. W., Souza-Pinto, N. C., Bohr, V. A., Rosenzweig, A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.035 · Cited by 950 · see citing works
Hirschey, M. D., Shimazu, T., Jing, E., Grueter, C. A., Collins, A. M., Aouizerat, B., Stančáková, A., Goetzman, E., Lam, M. M., Schwer, B., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.019 · Cited by 787 · see citing works
Self-citationLeigh syndrome: Clinical features and biochemical and DNA abnormalities
Rahman, S., Blok, R. B., Dahl, H. ‐. M., Danks, D. M., Kirby, D. M., Chow, C. W., Christodoulou, J., & Thorburn, D. R. (1996) · Annals of Neurology · doi:10.1002/ana.410390311 · Cited by 776 · see citing works
Linn, T. C., Pettit, F. H., & Reed, L. J. (1969) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.62.1.234 · Cited by 671 · see citing works
Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS
Chen, Y., Zhang, J., Lin, Y., Lei, Q., Guan, K., Zhao, S., & Xiong, Y. (2011) · The EMBO Reports · doi:10.1038/embor.2011.65 · Cited by 572 · see citing works
Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex
Bowker-Kinley, M. M., DAVIS, I. W., Wu, P., HARRIS, A. R., & POPOV, M. K. (1998) · Biochemical Journal · doi:10.1042/bj3290191 · Cited by 567 · see citing works
Metabolic flexibility and insulin resistance
Galgani, J. E., Moro, C., & Ravussin, E. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90558.2008 · Cited by 532 · cited 1× · see citing works
“Metabolic flexibility is the ability of an organism to adapt fuel oxidation in response to fuel availability (47).”
BackgroundDiet 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
Jing, E., Emanuelli, B., Hirschey, M. D., Boucher, J., Lee, K. Y., Lombard, D., Verdin, E. M., & Kahn, C. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111308108 · Cited by 469 · see citing works
Self-citationBefroy, D. E., Petersen, K. F., Dufour, S., Mason, G. F., de Graaf, R. A., Rothman, D. L., & Shulman, G. I. (2007) · Diabetes · doi:10.2337/db06-0783 · Cited by 453 · see citing works
An, J., Muoio, D. M., Shiota, M., Fujimoto, Y., Cline, G. W., Shulman, G. I., Koves, T. R., Stevens, R., Millington, D., & Newgard, C. B. (2004) · Nature Medicine · doi:10.1038/nm995 · Cited by 450 · see citing works
Self-citationSchilling, B., Rardin, M. J., MacLean, B., Zawadzka, A. M., Frewen, B. E., Cusack, M. P., Sorensen, D. J., Bereman, M. S., Jing, E., Wu, C. C., et al. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.017707 · Cited by 441 · see citing works
Self-citationBell, E. L., Emerling, B. M., Ricoult, S. J. H., & Guarente, L. (2011) · Oncogene · doi:10.1038/onc.2011.37 · Cited by 440 · see citing works
PREPARATION AND CHARACTERIZATION OF A PLASMA MEMBRANE FRACTION FROM ISOLATED FAT CELLS
McKeel, D. W., & Jarett, L. (1970) · The Journal of Cell Biology · doi:10.1083/jcb.44.2.417 · Cited by 401 · see citing works
Patterns of gene expression in atrophying skeletal muscles: response to food deprivation
Jagoe, R. T., Lecker, S. H., Gomes, M., & Goldberg, A. L. (2002) · The FASEB Journal · doi:10.1096/fj.02-0312com · Cited by 344 · see citing works
Regulation of the activity of the pyruvate dehydrogenase complex
Harris, R. A., Bowker-Kinley, M. M., Huang, B., & Wu, P. (2002) · Advances in Enzyme Regulation · doi:10.1016/s0065-2571(01)00061-9 · Cited by 337 · see citing works
Storlien, L., Oakes, N. D., & Kelley, D. E. (2004) · Proceedings of the Nutrition Society · doi:10.1079/pns2004349 · Cited by 291 · see citing works
Wu, P., Inskeep, K., Bowker-Kinley, M. M., Popov, K. M., & Harris, R. A. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1593 · Cited by 290 · see citing works
The Sirtuin family: therapeutic targets to treat diseases of aging
Milne, J. C., & Denu, J. M. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.01.019 · Cited by 271 · see citing works
Finck, 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 · see citing works
Calorie restriction alters mitochondrial protein acetylation
Schwer, B., Eckersdorff, M., Li, Y., Silva, J. C., Fermin, D., Kurtev, M. V., Giallourakis, C., Comb, M. J., Alt, F. W., & Lombard, D. B. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00503.x · Cited by 259 · see citing works
Use of intramuscular triacylglycerol as a substrate source during exercise in humans
van Loon, L. J. C. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00368.2004 · Cited by 205 · see citing works
Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4
Kim, J. K., Zisman, A., Fillmore, J. J., Peroni, O. D., Kotani, K., Perret, P., Zong, H., Dong, J., Kahn, C. R., Kahn, B. B., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10294 · Cited by 202 · cited 1× · see citing works
“In the fed state, the main fuel source in muscle is insulin-induced glucose metabolism (1,2); during fasting, muscle switches its fuel utilization from glucose to lipid oxidation (3).”
BackgroundSelf-citationGoodyear, L. J., Giorgino, F., Balon, T. W., Condorelli, G., & Smith, R. J. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.268.5.e987 · Cited by 176 · see citing works
Monitoring phosphorylation of the pyruvate dehydrogenase complex
Rardin, M. J., Wiley, S. E., Naviaux, R. K., Murphy, A. N., & Dixon, J. E. (2009) · Analytical Biochemistry · doi:10.1016/j.ab.2009.03.040 · Cited by 152 · see citing works
Self-citationAlpha-Keto Acid Dehydrogenase Complexes
Patel, M. S., Roche, T. E., & Harris, R. A. (1996) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8981-0 · Cited by 149 · see citing works
Compensatory Responses to Pyruvate Carboxylase Suppression in Islet β-Cells
Jensen, M. V., Joseph, J. W., Ilkayeva, O., Burgess, S. C., Lu, D., Ronnebaum, S. M., Odegaard, M. L., Becker, T. C., Sherry, A. D., & Newgard, C. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604350200 · Cited by 144 · see citing works
Self-citationRole 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 · see citing works
Fernandez-Marcos, P. J., Jeninga, E. H., Canto, C., Harach, T., de Boer, V. C. J., Andreux, P., Moullan, N., Pirinen, E., Yamamoto, H., Houten, S. M., et al. (2012) · Scientific Reports · doi:10.1038/srep00425 · Cited by 137 · see citing works
The human SIRT3 protein deacetylase is exclusively mitochondrial
Cooper, H. M., & Spelbrink, J. N. (2008) · Biochemical Journal · doi:10.1042/bj20071624 · Cited by 133 · see citing works
Summermatter, S., Baum, O., Santos, G., Hoppeler, H. H., & Handschin, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.145995 · Cited by 114 · see citing works
Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle
Bouskila, M., Hirshman, M. F., Jensen, J., Goodyear, L. J., & Sakamoto, K. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00481.2007 · Cited by 113 · see citing works
Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity
Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E., Han, D.-H., Nolte, L. A., Ojuka, E. O., Chen, M. W., & Holloszy, J. O. (2003) · The FASEB Journal · doi:10.1096/fj.03-0049com · Cited by 106 · see citing works
Wu, J.-Y., Kao, H., Li, S., Stevens, R., Hillman, S. L., Millington, D. S., & Chen, Y.-T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19574 · Cited by 104 · see citing works
PDH kinase inhibitors: a novel therapy for Type II diabetes?
Mayers, R. M., Leighton, B., & Kilgour, E. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330367 · Cited by 86 · see citing works
Muscle contractile activity regulates Sirt3 protein expression in rat skeletal muscles
Hokari, F., Kawasaki, E., Sakai, A., Koshinaka, K., Sakuma, K., & Kawanaka, K. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00335.2009 · Cited by 76 · see citing works
Espinoza, D., Boros, L. G., Crunkhorn, S., Gami, H., & Patti, M. (2009) · The FASEB Journal · doi:10.1096/fj.09-133728 · Cited by 60 · see citing works
Chow, L. S., From, A. H. L., & Seaquist, E. R. (2009) · Metabolism · doi:10.1016/j.metabol.2009.07.009 · Cited by 53 · see citing works
Deficiency of pyruvate dehydrogenase caused by novel and known mutations in the E1α subunit
Cameron, J. M., Levandovskiy, V., MacKay, N., et al. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30287 · Cited by 44 · see citing works
Fueger, P. T., Hess, H. S., Bracy, D. P., Pencek, R., Posey, K. A., Charron, M. J., & Wasserman, D. H. (2004) · Endocrinology · doi:10.1210/en.2004-0465 · Cited by 41 · see citing works
Akhmedov, D., Marchi, U. D., Wollheim, C. B., & Wiederkehr, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.07.005 · Cited by 25 · see citing works
Assays of Pyruvate Dehydrogenase Complex and Pyruvate Carboxylase Activity
Kerr, D. S., Grahame, G. J., & Nakouzi, G. A. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-504-6_7 · Cited by 17 · see citing works
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Mathias, R. A., Greco, T. M., Oberstein, A., Budayeva, H. G., Chakrabarti, R., Rowland, E. A., Kang, Y., Shenk, T., & Cristea, I. M. (2014) · Cell · doi:10.1016/j.cell.2014.11.046 · Cited by 430 · see citing works
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Muoio, D. M. (2014) · Cell · doi:10.1016/j.cell.2014.11.034 · Cited by 438 · see citing works
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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
Carrico, C., Meyer, J. G., He, W., Gibson, B. W., & Verdin, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.016 · Cited by 331 · see citing works
Self-citationFan, J., Shan, C., Kang, H.-B., Elf, S., Xie, J., Tucker, M., Gu, T.-L., Aguiar, M., Lonning, S., Chen, H., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.026 · Cited by 305 · see citing works
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Poulose, N., & Raju, R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.017 · Cited by 236 · see citing works
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McDonnell, E., Peterson, B. S., Bomze, H. M., & Hirschey, M. D. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.06.001 · Cited by 217 · see citing works
Paulin, R., Dromparis, P., Sutendra, G., Gurtu, V., Zervopoulos, S., Bowers, L., Haromy, A., Webster, L., Provencher, S., Bonnet, S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.08.011 · Cited by 214 · see citing works
Lantier, L., Williams, A. S., Williams, I. M., Yang, K. K., Bracy, D. P., Goelzer, M., James, F. D., Gius, D., & Wasserman, D. H. (2015) · Diabetes · doi:10.2337/db14-1810 · Cited by 151 · see citing works
Turn up the power - pharmacological activation of mitochondrial biogenesis in mouse models
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Lippi, L., de Sire, A., Mezian, K., Curci, C., Perrero, L., Turco, A., Andaloro, S., Ammendolia, A., Fusco, N., & Invernizzi, M. (2022) · Aging Clinical and Experimental Research · doi:10.1007/s40520-021-02073-w · Cited by 65 · see citing works
Lamb, D. A., Moore, J. H., Mesquita, P. H. C., Smith, M. A., Vann, C. G., Osburn, S. C., Fox, C. D., Lopez, H. L., Ziegenfuss, T. N., Huggins, K. W., et al. (2020) · Aging · doi:10.18632/aging.103218 · Cited by 62 · see citing works
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- Authors
- Jing, E., O’Neill, B. T., Rardin, M. J., Kleinridders, A., Ilkeyeva, O. R., Ussar, S., Bain, J. R., Lee, K. Y., Verdin, E. M., Newgard, C. B., Gibson, B. W., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
- Buck Institute for Research on Aging (US)
- Duke Medical Center (US)
- Gladstone Institutes (US)
- Corresponding author
- Kahn, C. Ronald
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-09-17
- Volume
- 62
- Issue
- 10
- Pages
- 3404-3417
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3781465
- OpenAlex
- W2159430439
- Cited by
- 283
- References
- 52
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 16 · 2023: 18 · 2022: 24 · 2021: 28 · 2020: 21 · 2019: 24 · 2018: 28 · 2017: 17 · 2016: 22 · 2015: 26 · 2014: 24 · 2013: 2
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute on Aging (P30AG028716)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK085610, T32DK007260, P30DK036836)
- National Center for Research Resources (S10RR024615)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SIRT3, NAD+-dependent deacetylase, skeletal muscle, metabolic flexibility, pyruvate dehydrogenase, protein acetylation, glucose oxidation, fatty acid oxidation, lactic acid production, insulin signaling, fasting, myoblasts
- MeSH terms
- Acetylation, Acetyltransferases, Animals, Fasting, Male, Mice, Inbred C57BL, Mitochondria, Oxidation-Reduction, Blotting, Western, Gene Expression Regulation, Enzymologic, Gene Deletion, Mice, Knockout, Oxidative Stress, Muscle, Skeletal, Mice, Sirtuin 3
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 ›
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