Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation
Open accessAbstract
Diabetes risk increases significantly with age and correlates with lower oxidative capacity in muscle. Decreased expression of peroxisome proliferator-activated receptor-γ coactivator-1α ( Pgc-1α) and target gene pathways involved in mitochondrial oxidative phosphorylation are associated with muscle insulin resistance, but a causative role has not been established. We sought to determine whether a decline in Pgc-1α and oxidative gene expression occurs during aging and potentiates the development of age-associated insulin resistance. Muscle-specific Pgc-1α knockout (MKO) mice and wild-type littermate controls were aged for 2 yr. Genetic signatures of skeletal muscle (microarray and mRNA expression) and metabolic profiles (glucose homeostasis, mitochondrial metabolism, body composition, lipids, and indirect calorimetry) of mice were compared at 3, 12, and 24 mo of age. Microarray and gene set enrichment analysis highlighted decreased function of the electron transport chain as characteristic of both aging muscle and loss of Pgc-1α expression. Despite significant reductions in oxidative gene expression and succinate dehydrogenase activity, young mice lacking Pgc-1α in muscle had lower fasting glucose and insulin. Consistent with loss of oxidative capacity during aging, Pgc-1α and Pgc-1β expression were reduced in aged wild-type mouse muscle. Interestingly, the combination of age and loss of muscle Pgc-1α expression impaired glucose tolerance and led to increased fat mass, insulin resistance, and inflammatory markers in white adipose and liver tissues. Therefore, loss of Pgc-1α expression and decreased mitochondrial oxidative capacity contribute to worsening glucose tolerance and chronic systemic inflammation associated with aging.
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Reductions in muscle function/respiratory capacity associated with decline in NOX4 might create a vicious cycle, further compromising exercise-induced antioxidant defense and contributing to age-associated decline in insulin sensitivity.
“Moreover, although defective mitochondrial biogenesis per se does not promote insulin resistance (52, 53), any reductions in muscle function/respiratory capacity associated with the decline in NOX4 might be expected to create a vicious cycle, further compromising exercise-induced antioxidant defense and contributing to the age-associated decline in insulin sensitivity.”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [53]
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1 retracted
Wenz, T., Rossi, S. G., Rotundo, R. L., Spiegelman, B. M., & Moraes, C. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911570106 · Cited by 600 · see citing works
RetractedMootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810 · see citing works
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · see citing works
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754 · see citing works
Type 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737 · see citing works
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · see citing works
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Oxidative damage and mitochondrial decay in aging.
Shigenaga, M. K., Hagen, T. M., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10771 · Cited by 2,055 · see citing works
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952 · see citing works
PGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Finck, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27794 · Cited by 1,427 · see citing works
Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice
Lin, J., Wu, P.-H., Tarr, P. T., Lindenberg, K. S., St-Pierre, J., Zhang, C.-Y., Mootha, V. K., Jäger, S., Vianna, C. R., Reznick, R. M., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.013 · Cited by 1,162 · see citing works
Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
Barrès, R., Yan, J., Egan, B., Treebak, J. T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D. J., & Zierath, J. R. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.001 · Cited by 965 · cited 1× · see citing works
“Expression of Pgc-1 in muscle is low in type 2 diabetics and related family members (2, 21, 33, 38) but can be increased with exercise to possibly prevent or reverse metabolic abnormalities (3, 25, 44, 49).”
BackgroundLeone, 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
Excessive Loss of Skeletal Muscle Mass in Older Adults With Type 2 Diabetes
Park, S. W., Goodpaster, B. H., Lee, J. S., Kuller, L. H., Boudreau, R., de Rekeneire, N., Harris, T. B., Kritchevsky, S., Tylavsky, F. A., Nevitt, M., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0264 · Cited by 778 · see citing works
Mootha, V. K., Handschin, C., Arlow, D., Xie, X., St. Pierre, J., Sihag, S., Yang, W., Altshuler, D., Puigserver, P., Patterson, N., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401401101 · Cited by 688 · see citing works
A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy
Ruas, J. L., White, J. P., Rao, R. R., Kleiner, S., Brannan, K. T., Harrison, B. C., Greene, N. P., Wu, J., Estall, J. L., Irving, B. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.050 · Cited by 677 · see citing works
Self-citationMichael, L. F., Wu, Z., Cheatham, R. B., Puigserver, P., Adelmant, G., Lehman, J. J., Kelly, D. P., & Spiegelman, B. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061035098 · Cited by 663 · see citing works
Handschin, C., Chin, S., Li, P., Liu, F., Maratos-Flier, E., LeBrasseur, N. K., Yan, Z., & Spiegelman, B. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704817200 · Cited by 611 · see citing works
Non-CpG methylation of the PGC-1α promoter through DNMT3B controls mitochondrial density.
Barrès, R., Osler, M. E., Yan, J., Rune, A., Fritz, T., Caidahl, K., Krook, A., & Zierath, J. R. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.07.011 · Cited by 602 · see citing works
Pospisilik, J. A., Knauf, C., Joza, N., Benit, P., Orthofer, M., Cani, P. D., Ebersberger, I., Nakashima, T., Sarao, R., Neely, G., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.047 · Cited by 404 · see citing works
PGC-1α regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophyPreprint
Handschin, C., Kobayashi, Y. M., Chin, S., Seale, P., Campbell, K. P., & Spiegelman, B. M. (2007) · Genes & Development · doi:10.1101/gad.1525107 · Cited by 355 · see citing works
Transcriptional profiling of aging in human muscle reveals a common aging signature
Zahn, J. M., Sonu, R., Vogel, H., Crane, E., Mazan-Mamczarz, K., Rabkin, R., Davis, R. W., Becker, K. G., Owen, A. B., & Kim, S. K. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020115 · Cited by 351 · see citing works
Handschin, C., Choi, C. S., Chin, S., Kim, S., Kawamori, D., Kurpad, A. J., Neubauer, N., Hu, J., Mootha, V. K., Kim, Y.-B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31785 · Cited by 335 · 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
Skeletal Muscle Mitochondria and Aging: A Review
Peterson, C. M., Johannsen, D. L., & Ravussin, É. (2012) · Journal of Aging Research · doi:10.1155/2012/194821 · Cited by 318 · see citing works
Wu, J., Ruas, J. L., Estall, J. L., Rasbach, K. A., Choi, J. H., Ye, L., Boström, P., Tyra, H. M., Crawford, R. W., Campbell, K. P., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.003 · Cited by 312 · see citing works
Self-citationLi, S., Czubryt, M. P., McAnally, J., Bassel‐Duby, R., Richardson, J. A., Wiebel, F. F., Nordheim, A., & Olson, E. N. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409103102 · Cited by 295 · see citing works
Development of insulin resistance in mice lacking PGC-1α in adipose tissues
Kleiner, S., Mepani, R. J., Laznik, D., Li, Y., Jurczak, M. J., Jornayvaz, F. R., Estall, J. L., Bhowmick, D. C., Shulman, G. I., & Spiegelman, B. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207287109 · Cited by 286 · see citing works
Self-citationChoi, C. S., Befroy, D. E., Codella, R., Kim, S., Reznick, R. M., Hwang, Y.-J., Liu, Z.-X., Lee, H.-Y., Distefano, A., Samuel, V. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810339105 · Cited by 279 · see citing works
Zechner, C., Lai, L., Zechner, J. F., Geng, T., Yan, Z., Rumsey, J. W., Collia, D., Chen, Z., Wozniak, D. F., Leone, T. C., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.008 · Cited by 274 · cited 16× · see citing works
“Overexpression of PGC-1 in muscle protects aging mice from age-related muscle wasting and glucose intolerance (50, 52), and yet tight regulation of PGC-1 expression is required to maintain efficient glucose and lipid handling in obese mice (6, 19, 51).”
BackgroundResultInfluentialThe Effect of Aging on Human Skeletal Muscle Mitochondrial and Intramyocellular Lipid Ultrastructure
Crane, J. D., Devries, M. C., Safdar, A., Hamadeh, M. J., & Tarnopolsky, M. A. (2010) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glp179 · Cited by 262 · see citing works
Skeletal muscle aging and the mitochondrion
Johnson, M. L., Robinson, M. M., & Nair, K. S. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.12.003 · Cited by 233 · see citing works
Hernández-Alvarez, M. I., Thabit, H., Burns, N., Shah, S., Brema, I., Hatunic, M., Finucane, F., Liesa, M., Chiellini, C., Naon, D., et al. (2010) · Diabetes Care · doi:10.2337/dc09-1305 · Cited by 189 · see citing works
Eisele, P. S., Salatino, S., Sobek, J., Hottiger, M. O., & Handschin, C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.375253 · Cited by 187 · see citing works
Álvarez-Guardia, D., Palomer, X., Coll, T., Davidson, M. M., Chan, T. O., Feldman, A. M., Laguna, J. C., & Vázquez‐Carrera, M. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq080 · Cited by 187 · see citing works
Effects of Obesity on Substrate Utilization during Exercise
Goodpaster, B. H., Wolfe, R. R., & Kelley, D. E. (2002) · Obesity Research · doi:10.1038/oby.2002.78 · Cited by 169 · see citing works
The immune system's involvement in obesity-driven type 2 diabetes
Shu, C. J., Benoist, C. O., & Mathis, D. J. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.001 · Cited by 165 · see citing works
Muscle mitochondrial changes with aging and exercise
Lanza, I. R., & Nair, K. S. (2008) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26717d · Cited by 152 · see citing works
Estall, J. L., Kahn, M., Cooper, M. P., Fisher, F. M., Wu, M. K., Laznik, D., Qu, L., Cohen, D. E., Shulman, G. I., & Spiegelman, B. M. (2009) · Diabetes · doi:10.2337/db08-1571 · Cited by 148 · see citing works
Self-citationRespiratory chain dysfunction in skeletal muscle does not cause insulin resistance
Wredenberg, A., Freyer, C., Sandström, M. E., Katz, A., Wibom, R., Westerblad, H., & Larsson, N.-G. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.09.029 · Cited by 141 · see citing works
Ghosh, S., Lertwattanarak, R., Lefort, N., Molina-Carrion, M., Joya-Galeana, J., Bowen, B. P., Garduno-Garcia, J. D. J., Abdul-Ghani, M., Richardson, A., DeFronzo, R. A., et al. (2011) · Diabetes · doi:10.2337/db11-0121 · Cited by 128 · see citing works
Mitochondrial Deficiency Is Associated With Insulin Resistance
Goodpaster, B. (2013) · Diabetes · doi:10.2337/db12-1612 · Cited by 123 · see citing works
The role of PGC‐1 coactivators in aging skeletal muscle and heart
Dillon, L. M., Rebelo, A. P., & Moraes, C. T. (2012) · IUBMB Life · doi:10.1002/iub.608 · Cited by 116 · see citing works
“Deficiency” of Mitochondria in Muscle Does Not Cause Insulin Resistance
Holloszy, J. O. (2013) · Diabetes · doi:10.2337/db12-1107 · Cited by 111 · see citing works
Exendin-4 modulates diabetes onset in nonobese diabetic mice
Hadjiyanni, I., Baggio, L. L., Poussier, P., & Drucker, D. J. (2008) · Endocrinology · doi:10.1210/en.2007-1137 · Cited by 110 · see citing works
Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes
Bergman, B. C., Howard, D., Schauer, I. E., Maahs, D. M., Snell‐Bergeon, J. K., Eckel, R. H., Perreault, L., & Rewers, M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3172 · Cited by 108 · see citing works
Rowe, G. C., Patten, I. S., Zsengellér, Z. K., El‐Khoury, R., Okutsu, M., Bampoh, S., Koulisis, N., Farrell, C., Hirshman, M. F., Yan, Z., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.023 · Cited by 104 · see citing works
PGC-1α Improves Glucose Homeostasis in Skeletal Muscle in an Activity-Dependent Manner
Summermatter, S., Shui, G., Maag, D., Santos, G., Wenk, M. R., & Handschin, C. (2012) · Diabetes · doi:10.2337/db12-0291 · Cited by 96 · see citing works
Ma, D., Li, S., Lucas, E. K., Cowell, R. M., & Lin, J. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.151688 · Cited by 73 · see citing works
Ringholm, S., Olesen, J., Pedersen, J. T., Brandt, C. T., Halling, J. F., Hellsten, Y., Prats, C., & Pilegaard, H. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.08.012 · Cited by 61 · see citing works
Mormeneo, E., Jimenez-Mallebrera, C., Palomer, X., Nigris, V. D., Vázquez‐Carrera, M., Orozco, A., Nascimento, A., Colomer, J., Lerín, C., & Gómez-Foix, A. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029985 · Cited by 54 · see citing works
Mitochondrial Function and Insulin Resistance during Aging – A Mini-Review
Phielix, E., Szendroedi, J., & Roden, M. (2011) · Gerontology · doi:10.1159/000317691 · Cited by 47 · see citing works
PGC-1α and exercise in the control of body weight
Summermatter, S., & Handschin, C. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.12 · Cited by 45 · see citing works
Olesen, J., Ringholm, S., Nielsen, M. M., Brandt, C. T., Pedersen, J. T., Halling, J. F., Goodyear, L. J., & Pilegaard, H. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.07.015 · Cited by 38 · see citing works
Summermatter, S., Troxler, H., Santos, G., & Handschin, C. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.04.012 · Cited by 27 · see citing works
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Research works printed but not linked: 1
- [27]Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M, Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM, Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol 3: e101, 2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
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Immune aging, dysmetabolism, and inflammation in neurological diseases
Deleidi, M., Jäggle, M., & Rubino, G. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00172 · Cited by 260 · see citing works
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- Authors
- Sczelecki, S., Besse-Patin, A., Abboud, A., Kleiner, S., Laznik-Bogoslavski, D., Wrann, C. D., Ruas, J. L., Haibe-Kains, B., & Estall, J. L.
- Affiliations
- McGill University (CA)
- Divisions of Cardiovascular and Metabolic Disease and
- Dana-Farber Cancer Institute (US)
- Karolinska Institutet (SE)
- Systems Biology and Medicinal Chemistry, Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada;
- Corresponding author
- Estall, Jennifer L.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2014-01-15
- Volume
- 306
- Issue
- 2
- Pages
- E157-E167
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC4073996
- OpenAlex
- W2121486568
- Cited by
- 108
- References
- 56
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 5 · 2023: 12 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 12 · 2018: 6 · 2017: 6 · 2016: 12 · 2015: 8 · 2014: 3
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Joslin Diabetes Center
- Novo Nordisk Fonden (NNF12OC1016062)
- National Institute of Diabetes and Digestive and Kidney Diseases (5 P30 DK-36836, P30DK036836)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- PGC-1α, PGC-1β, skeletal muscle aging, muscle insulin resistance, impaired glucose tolerance, mitochondrial oxidative capacity, electron transport chain, succinate dehydrogenase, muscle-specific knockout mice, systemic inflammation, fat mass, white adipose tissue, liver inflammation, glucose homeostasis
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Inflammation, Mice, Inbred C57BL, Mitochondria, Muscle, Oxidative Phosphorylation, Transcription Factors, Gene Deletion, Glucose Intolerance, Mice, Knockout, Muscle, Skeletal, Gene Expression Profiling, Microarray Analysis, Mice
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