The impact of exercise on gene regulation in association with complex trait genetics.
Nature communications
Vetr, N. G., Gay, N. R., MoTrPAC Study Group, Montgomery, S. B., Adkins, J. N., Albertson, B. G., Amar, D., Amper, M. A., Armenteros, J. J., Ashley, E., Avila-Pacheco, J., Bae, D., Balci, A. T., Bamman, M., Bararpour, N., Barton, E. R., Jean Beltran, P. M., Bergman, B. C., Bessesen, D. H., Bodine, S. C., Booth, F. W., Bouverat, B., Buford, T. W., Burant, C. F., Caputo, T., Carr, S., Chambers, T. L., Chavez, C., Chikina, M., Chiu, R., Cicha, M., Clish, C. B., Coen, P. M., Cooper, D., Cornell, E., Cutter, G., Dalton, K. P., Dasari, S., Dennis, C., Esser, K., Evans, C. R., Farrar, R., Fernadez, F. M., Gadde, K., Gagne, N., Gaul, D. A., Ge, Y., Gerszten, R. E., Goodpaster, B. H., Goodyear, L. J., Gritsenko, M. A., Guevara, K., Haddad, F., Hansen, J. R., Harris, M., Hastie, T., Hennig, K. M., Hershman, S. G., Hevener, A., Hirshman, M. F., Hou, Z., Hsu, F., Huffman, K. M., Hung, C., Hutchinson-Bunch, C., Ivanova, A. A., Jackson, B. E., Jankowski, C. M., Jimenez-Morales, D., Jin, C. A., Johannsen, N. M., Newton, R. L., Kachman, M. T., Ke, B. G., Keshishian, H., Kohrt, W. M., Kramer, K. S., Kraus, W. E., Lanza, I., Leeuwenburgh, C., Lessard, S. J., Lester, B., Li, J. Z., Lindholm, M. E., Lira, A. K., Liu, X., Lu, C., Makarewicz, N. S., Maner-Smith, K. M., Mani, D. R., Many, G. M., Marjanovic, N., Marshall, A., Marwaha, S., May, S., Melanson, E. L., Miller, M. E., Monroe, M. E., Moore, S. G., Moore, R. J., Moreau, K. L., Mundorff, C. C., Musi, N., Nachun, D., Nair, V. D., Nair, K. S., Nestor, M. D., Nicklas, B., Nigro, P., Nudelman, G., Ortlund, E. A., Pahor, M., Pearce, C., Petyuk, V. A., Piehowski, P. D., Pincas, H., Powers, S., Presby, D. M., Qian, W., Radom-Aizik, S., Raja, A. N., Ramachandran, K., Ramaker, M. E., Ramos, I., Rankinen, T., Raskind, A. S., Rasmussen, B. B., Ravussin, E., Rector, R. S., Rejeski, W. J., Richards, C. Z., Rirak, S., Robbins, J. M., Rooney, J. L., Rubenstein, A. B., Ruf-Zamojski, F., Rushing, S., Sagendorf, T. J., Samdarshi, M., Sanford, J. A., Savage, E. M., Schauer, I. E., Schenk, S., Schwartz, R. S., Sealfon, S. C., Seenarine, N., Smith, K. S., Smith, G. R., Snyder, M. P., Soni, T., Oliveira De Sousa, L. G., Sparks, L. M., Steep, A., Stowe, C. L., Sun, Y., Teng, C., Thalacker-Mercer, A., Thyfault, J., Tibshirani, R., Tracy, R., Trappe, S., Trappe, T. A., Uppal, K., Vangeti, S., Vasoya, M., Volpi, E., Vornholt, A., Walkup, M. P., Walsh, M. J., Wheeler, M. T., Williams, J. P., Wu, S., Xia, A., Yan, Z., Yu, X., Zang, C., Zaslavsky, E., Zebarjadi, N., Zhang, T., Zhao, B., Zhen, J.
2024; 15 (1): 3346
Abstract
Endurance exercise training is known to reduce risk for a range of complex diseases. However, the molecular basis of this effect has been challenging to study and largely restricted to analyses of either few or easily biopsied tissues. Extensive transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium has provided a unique opportunity to clarify how exercise can affect tissue-specific gene expression and further suggest how exercise adaptation may impact complex disease-associated genes. To build this map, we integrate this multi-tissue atlas of gene expression changes with gene-disease targets, genetic regulation of expression, and trait relationship data in humans. Consensus from multiple approaches prioritizes specific tissues and genes where endurance exercise impacts disease-relevant gene expression. Specifically, we identify a total of 5523 trait-tissue-gene triplets to serve as a valuable starting point for future investigations [Exercise; Transcription; Human Phenotypic Variation].
View details for DOI 10.1038/s41467-024-45966-w
View details for PubMedID 38693125
Temporal dynamics of the multi-omic response to endurance exercise training.
Nature
2024; 629 (8010): 174-183
Abstract
Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).
View details for DOI 10.1038/s41586-023-06877-w
View details for PubMedID 38693412
View details for PubMedCentralID PMC11062907
Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue.
Nature metabolism
Many, G. M., Sanford, J. A., Sagendorf, T. J., Hou, Z., Nigro, P., Whytock, K. L., Amar, D., Caputo, T., Gay, N. R., Gaul, D. A., Hirshman, M. F., Jimenez-Morales, D., Lindholm, M. E., Muehlbauer, M. J., Vamvini, M., Bergman, B. C., Fernandez, F. M., Goodyear, L. J., Hevener, A. L., Ortlund, E. A., Sparks, L. M., Xia, A., Adkins, J. N., Bodine, S. C., Newgard, C. B., Schenk, S., MoTrPAC Study Group, Armenteros, J. J., Amper, M. A., Ashley, E., Asokan, A. K., Avila-Pacheco, J., Bae, D., Bamman, M. M., Bararpour, N., Barnes, J., Buford, T. W., Burant, C. F., Carbone, N. P., Carr, S. A., Chambers, T. L., Chavez, C., Chiu, R., Clish, C. B., Cutter, G. R., Dasari, S., Dennis, C., Evans, C. R., Fernandez, F. M., Gagne, N., Ge, Y., Goodpaster, B. H., Gritsenko, M. A., Hansen, J. R., Hennig, K. M., Huffman, K. M., Hung, C., Hutchinson-Bunch, C., Ilkayeva, O., Ivanova, A. A., Beltran, P. M., Jin, C. A., Kachman, M. T., Keshishian, H., Kraus, W. E., Lanza, I., Lester, B., Li, J. Z., Lira, A. K., Liu, X., Maner-Smith, K. M., May, S., Monroe, M. R., Montgomery, S., Moore, R. J., Moore, S. G., Nachun, D., Nair, K. S., Nair, V., Raja, A. N., Nestor, M. D., Nudelman, G., Petyuk, V. A., Piehowski, P. D., Pincas, H., Qian, W., Raskind, A., Rasmussen, B. B., Rooney, J. L., Rushing, S., Samdarshi, M., Sealfon, S. C., Smith, K. S., Smith, G. R., Snyder, M., Stowe, C. L., Talton, J. W., Teng, C., Thalacker-Mercer, A., Tracy, R., Trappe, T. A., Vasoya, M., Vetr, N. G., Volpi, E., Walkup, M. P., Walsh, M. J., Wheeler, M. T., Wu, S., Zaslavsky, E., Zebarjadi, N., Zhang, T., Zhao, B., Zhen, J.
2024
Abstract
Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.
View details for DOI 10.1038/s42255-023-00959-9
View details for PubMedID 38693320
Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.
Cell genomics
Nair, V. D., Pincas, H., Smith, G. R., Zaslavsky, E., Ge, Y., Amper, M. A., Vasoya, M., Chikina, M., Sun, Y., Raja, A. N., Mao, W., Gay, N. R., Esser, K. A., Smith, K. S., Zhao, B., Wiel, L., Singh, A., Lindholm, M. E., Amar, D., Montgomery, S., Snyder, M. P., Walsh, M. J., Sealfon, S. C., MoTrPAC Study Group
2024: 100421
Abstract
Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.
View details for DOI 10.1016/j.xgen.2023.100421
View details for PubMedID 38697122
The mitochondrial multi-omic response to exercise training across rat tissues.
Cell metabolism
Amar, D., Gay, N. R., Jimenez-Morales, D., Jean Beltran, P. M., Ramaker, M. E., Raja, A. N., Zhao, B., Sun, Y., Marwaha, S., Gaul, D. A., Hershman, S. G., Ferrasse, A., Xia, A., Lanza, I., Fernández, F. M., Montgomery, S. B., Hevener, A. L., Ashley, E. A., Walsh, M. J., Sparks, L. M., Burant, C. F., Rector, R. S., Thyfault, J., Wheeler, M. T., Goodpaster, B. H., Coen, P. M., Schenk, S., Bodine, S. C., Lindholm, M. E.
2024
Abstract
Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart, and skeletal muscle. The colon showed non-linear response dynamics, whereas mitochondrial pathways were downregulated in brown adipose and adrenal tissues. Protein acetylation increased in the liver, with a shift in lipid metabolism, whereas oxidative proteins increased in striated muscles. Exercise-upregulated networks were downregulated in human diabetes and cirrhosis. Knockdown of the central network protein 17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) elevated oxygen consumption, indicative of metabolic stress. We provide a multi-omic, multi-tissue, temporal atlas of the mitochondrial response to exercise training and identify candidates linked to mitochondrial dysfunction.
View details for DOI 10.1016/j.cmet.2023.12.021
View details for PubMedID 38701776
Author Correction: Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP).
Nature cell biology
Jain, S., Pei, L., Spraggins, J. M., Angelo, M., Carson, J. P., Gehlenborg, N., Ginty, F., Goncalves, J. P., Hagood, J. S., Hickey, J. W., Kelleher, N. L., Laurent, L. C., Lin, S., Lin, Y., Liu, H., Naba, A., Nakayasu, E. S., Qian, W., Radtke, A., Robson, P., Stockwell, B. R., Van de Plas, R., Vlachos, I. S., Zhou, M., HuBMAP Consortium, Borner, K., Snyder, M. P., Ahn, K. J., Allen, J., Anderson, D. M., Anderton, C. R., Curcio, C., Angelin, A., Arvanitis, C., Atta, L., Awosika-Olumo, D., Bahmani, A., Bai, H., Balderrama, K., Balzano, L., Bandyopadhyay, G., Bandyopadhyay, S., Bar-Joseph, Z., Barnhart, K., Barwinska, D., Becich, M., Becker, L., Becker, W., Bedi, K., Bendall, S., Benninger, K., Betancur, D., Bettinger, K., Billings, S., Blood, P., Bolin, D., Border, S., Bosse, M., Bramer, L., Brewer, M., Brusko, M., Bueckle, A., Burke, K., Burnum-Johnson, K., Butcher, E., Butterworth, E., Cai, L., Calandrelli, R., Caldwell, M., Campbell-Thompson, M., Cao, D., Cao-Berg, I., Caprioli, R., Caraccio, C., Caron, A., Carroll, M., Chadwick, C., Chen, A., Chen, D., Chen, F., Chen, H., Chen, J., Chen, L., Chen, L., Chiacchia, K., Cho, S., Chou, P., Choy, L., Cisar, C., Clair, G., Clarke, L., Clouthier, K. A., Colley, M. E., Conlon, K., Conroy, J., Contrepois, K., Corbett, A., Corwin, A., Cotter, D., Courtois, E., Cruz, A., Csonka, C., Czupil, K., Daiya, V., Dale, K., Davanagere, S. A., Dayao, M., de Caestecker, M. P., Decker, A., Deems, S., Degnan, D., Desai, T., Deshpande, V., Deutsch, G., Devlin, M., Diep, D., Dodd, C., Donahue, S., Dong, W., Dos Santos Peixoto, R., Duffy, M., Dufresne, M., Duong, T. E., Dutra, J., Eadon, M. T., El-Achkar, T. M., Enninful, A., Eraslan, G., Eshelman, D., Espin-Perez, A., Esplin, E. D., Esselman, A., Falo, L. D., Falo, L., Fan, J., Fan, R., Farrow, M. A., Farzad, N., Favaro, P., Fermin, J., Filiz, F., Filus, S., Fisch, K., Fisher, E., Fisher, S., Flowers, K., Flynn, W. F., Fogo, A. B., Fu, D. A., Fulcher, J., Fung, A., Furst, D., Gallant, M., Gao, F., Gao, Y., Gaulton, K., Gaut, J. P., Gee, J., Ghag, R. R., Ghazanfar, S., Ghose, S., Gisch, D., Gold, I., Gondalia, A., Gorman, B., Greenleaf, W., Greenwald, N., Gregory, B., Guo, R., Gupta, R., Hakimian, H., Haltom, J., Halushka, M., Han, K. S., Hanson, C., Harbury, P., Hardi, J., Harlan, L., Harris, R. C., Hartman, A., Heidari, E., Helfer, J., Helminiak, D., Hemberg, M., Henning, N., Herr, B. W., Ho, J., Holden-Wiltse, J., Hong, S., Hong, Y., Honick, B., Hood, G., Hu, P., Hu, Q., Huang, M., Huyck, H., Imtiaz, T., Isberg, O. G., Itkin, M., Jackson, D., Jacobs, M., Jain, Y., Jewell, D., Jiang, L., Jiang, Z. G., Johnston, S., Joshi, P., Ju, Y., Judd, A., Kagel, A., Kahn, A., Kalavros, N., Kalhor, K., Karagkouni, D., Karathanos, T., Karunamurthy, A., Katari, S., Kates, H., Kaushal, M., Keener, N., Keller, M., Kenney, M., Kern, C., Kharchenko, P., Kim, J., Kingsford, C., Kirwan, J., Kiselev, V., Kishi, J., Kitata, R. B., Knoten, A., Kollar, C., Krishnamoorthy, P., Kruse, A. R., Da, K., Kundaje, A., Kutschera, E., Kwon, Y., Lake, B. B., Lancaster, S., Langlieb, J., Lardenoije, R., Laronda, M., Laskin, J., Lau, K., Lee, H., Lee, M., Lee, M., Strekalova, Y. L., Li, D., Li, J., Li, J., Li, X., Li, Z., Liao, Y., Liaw, T., Lin, P., Lin, Y., Lindsay, S., Liu, C., Liu, Y., Liu, Y., Lott, M., Lotz, M., Lowery, L., Lu, P., Lu, X., Lucarelli, N., Lun, X., Luo, Z., Ma, J., Macosko, E., Mahajan, M., Maier, L., Makowski, D., Malek, M., Manthey, D., Manz, T., Margulies, K., Marioni, J., Martindale, M., Mason, C., Mathews, C., Maye, P., McCallum, C., McDonough, E., McDonough, L., Mcdowell, H., Meads, M., Medina-Serpas, M., Ferreira, R. M., Messinger, J., Metis, K., Migas, L. G., Miller, B., Mimar, S., Minor, B., Misra, R., Missarova, A., Mistretta, C., Moens, R., Moerth, E., Moffitt, J., Molla, G., Monroe, M., Monte, E., Morgan, M., Muraro, D., Murphy, B. R., Murray, E., Musen, M. A., Naglah, A., Nasamran, C., Neelakantan, T., Nevins, S., Nguyen, H., Nguyen, N., Nguyen, T., Nguyen, T., Nigra, D., Nofal, M., Nolan, G., Nwanne, G., O'Connor, M., Okuda, K., Olmer, M., O'Neill, K., Otaluka, N., Pang, M., Parast, M., Pasa-Tolic, L., Paten, B., Patterson, N. H., Peng, T., Phillips, G., Pichavant, M., Piehowski, P., Pilner, H., Pingry, E., Pita-Juarez, Y., Plevritis, S., Ploumakis, A., Pouch, A., Pryhuber, G., Puerto, J., Qaurooni, D., Qin, L., Quardokus, E. M., Rajbhandari, P., Rakow-Penner, R., Ramasamy, R., Read, D., Record, E. G., Reeves, D., Ricarte, A., Rodriguez-Soto, A., Ropelewski, A., Rosario, J., Roselkis, M., Rowe, D., Roy, T. K., Ruffalo, M., Ruschman, N., Sabo, A., Sachdev, N., Saka, S., Salamon, D., Sarder, P., Sasaki, H., Satija, R., Saunders, D., Sawka, R., Schey, K., Schlehlein, H., Scholten, D., Schultz, S., Schwartz, L., Schwenk, M., Scibek, R., Segre, A., Serrata, M., Shands, W., Shen, X., Shendure, J., Shephard, H., Shi, L., Shi, T., Shin, D., Shirey, B., Sibilla, M., Silber, M., Silverstein, J., Simmel, D., Simmons, A., Singhal, D., Sivajothi, S., Smits, T., Soncin, F., Song, Q., Stanley, V., Stuart, T., Su, H., Su, P., Sun, X., Surrette, C., Swahn, H., Tan, K., Teichmann, S., Tejomay, A., Tellides, G., Thomas, K., Thomas, T., Thompson, M., Tian, H., Tideman, L., Trapnell, C., Tsai, A. G., Tsai, C., Tsai, L., Tsui, E., Tsui, T., Tung, J., Turner, M., Uranic, J., Vaishnav, E. D., Varra, S. R., Vaskivskyi, V., Velickovic, D., Velickovic, M., Verheyden, J., Waldrip, J., Wallace, D., Wan, X., Wang, A., Wang, F., Wang, M., Wang, S., Wang, X., Wasserfall, C., Wayne, L., Webber, J., Weber, G. M., Wei, B., Wei, J., Weimer, A., Welling, J., Wen, X., Wen, Z., Williams, M., Winfree, S., Winograd, N., Woodard, A., Wright, D., Wu, F., Wu, P., Wu, Q., Wu, X., Xing, Y., Xu, T., Yang, M., Yang, M., Yap, J., Ye, D. H., Yin, P., Yuan, Z., Yun, C. J., Zahraei, A., Zemaitis, K., Zhang, B., Zhang, C., Zhang, C., Zhang, C., Zhang, K., Zhang, S., Zhang, T., Zhang, Y., Zhao, B., Zhao, W., Zheng, J. W., Zhong, S., Zhu, B., Zhu, C., Zhu, D., Zhu, Q., Zhu, Y.
2024
Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP).
Nature cell biology
Jain, S., Pei, L., Spraggins, J. M., Angelo, M., Carson, J. P., Gehlenborg, N., Ginty, F., Gonçalves, J. P., Hagood, J. S., Hickey, J. W., Kelleher, N. L., Laurent, L. C., Lin, S., Lin, Y., Liu, H., Naba, A., Nakayasu, E. S., Qian, W. J., Radtke, A., Robson, P., Stockwell, B. R., Van de Plas, R., Vlachos, I. S., Zhou, M., Börner, K., Snyder, M. P.
2023
Abstract
The Human BioMolecular Atlas Program (HuBMAP) aims to create a multi-scale spatial atlas of the healthy human body at single-cell resolution by applying advanced technologies and disseminating resources to the community. As the HuBMAP moves past its first phase, creating ontologies, protocols and pipelines, this Perspective introduces the production phase: the generation of reference spatial maps of functional tissue units across many organs from diverse populations and the creation of mapping tools and infrastructure to advance biomedical research.
View details for DOI 10.1038/s41556-023-01194-w
View details for PubMedID 37468756
View details for PubMedCentralID 8238499
Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise.
Cell
Sanford, J. A., Nogiec, C. D., Lindholm, M. E., Adkins, J. N., Amar, D., Dasari, S., Drugan, J. K., Fernandez, F. M., Radom-Aizik, S., Schenk, S., Snyder, M. P., Tracy, R. P., Vanderboom, P., Trappe, S., Walsh, M. J., Molecular Transducers of Physical Activity Consortium, Adkins, J. N., Amar, D., Dasari, S., Drugan, J. K., Evans, C. R., Fernandez, F. M., Li, Y., Lindholm, M. E., Nogiec, C. D., Radom-Aizik, S., Sanford, J. A., Schenk, S., Snyder, M. P., Tomlinson, L., Tracy, R. P., Trappe, S., Vanderboom, P., Walsh, M. J., Alekel, D. L., Bekirov, I., Boyce, A. T., Boyington, J., Fleg, J. L., Joseph, L. J., Laughlin, M. R., Maruvada, P., Morris, S. A., McGowan, J. A., Nierras, C., Pai, V., Peterson, C., Ramos, E., Roary, M. C., Williams, J. P., Xia, A., Cornell, E., Rooney, J., Miller, M. E., Ambrosius, W. T., Rushing, S., Stowe, C. L., Rejeski, W. J., Nicklas, B. J., Pahor, M., Lu, C., Trappe, T., Chambers, T., Raue, U., Lester, B., Bergman, B. C., Bessesen, D. H., Jankowski, C. M., Kohrt, W. M., Melanson, E. L., Moreau, K. L., Schauer, I. E., Schwartz, R. S., Kraus, W. E., Slentz, C. A., Huffman, K. M., Johnson, J. L., Willis, L. H., Kelly, L., Houmard, J. A., Dubis, G., Broskey, N., Goodpaster, B. H., Sparks, L. M., Coen, P. M., Cooper, D. M., Haddad, F., Rankinen, T., Ravussin, E., Johannsen, N., Harris, M., Jakicic, J. M., Newman, A. B., Forman, D. D., Kershaw, E., Rogers, R. J., Nindl, B. C., Page, L. C., Stefanovic-Racic, M., Barr, S. L., Rasmussen, B. B., Moro, T., Paddon-Jones, D., Volpi, E., Spratt, H., Musi, N., Espinoza, S., Patel, D., Serra, M., Gelfond, J., Burns, A., Bamman, M. M., Buford, T. W., Cutter, G. R., Bodine, S. C., Esser, K., Farrar, R. P., Goodyear, L. J., Hirshman, M. F., Albertson, B. G., Qian, W., Piehowski, P., Gritsenko, M. A., Monore, M. E., Petyuk, V. A., McDermott, J. E., Hansen, J. N., Hutchison, C., Moore, S., Gaul, D. A., Clish, C. B., Avila-Pacheco, J., Dennis, C., Kellis, M., Carr, S., Jean-Beltran, P. M., Keshishian, H., Mani, D. R., Clauser, K., Krug, K., Mundorff, C., Pearce, C., Ivanova, A. A., Ortlund, E. A., Maner-Smith, K., Uppal, K., Zhang, T., Sealfon, S. C., Zavlasky, E., Nair, V., Li, S., Jain, N., Ge, Y., Sun, Y., Nudelman, G., Ruf-Zamojski, F., Smith, G., Pincas, N., Rubenstein, A., Amper, M. A., Seenarine, N., Lappalainen, T., Lanza, I. R., Nair, K. S., Klaus, K., Montgomery, S. B., Smith, K. S., Gay, N. R., Zhao, B., Hung, C. J., Zebarjadi, N., Balliu, B., Fresard, L., Burant, C. F., Li, J. Z., Kachman, M., Soni, T., Raskind, A. B., Gerszten, R., Robbins, J., Ilkayeva, O., Muehlbauer, M. J., Newgard, C. B., Ashley, E. A., Wheeler, M. T., Jimenez-Morales, D., Raja, A., Dalton, K. P., Zhen, J., Kim, Y. S., Christle, J. W., Marwaha, S., Chin, E. T., Hershman, S. G., Hastie, T., Tibshirani, R., Rivas, M. A.
2020; 181 (7): 1464–74
Abstract
Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.
View details for DOI 10.1016/j.cell.2020.06.004
View details for PubMedID 32589957
The role of translationally controlled tumor protein in proliferation of Drosophila intestinal stem cells.
Proceedings of the National Academy of Sciences of the United States of America
Kwon, Y. V., Zhao, B., Xu, C., Lee, J., Chen, C. L., Vinayagam, A., Edgar, B. A., Perrimon, N.
2019
Abstract
Translationally controlled tumor protein (TCTP) is a highly conserved protein functioning in multiple cellular processes, ranging from growth to immune responses. To explore the role of TCTP in tissue maintenance and regeneration, we employed the adult Drosophila midgut, where multiple signaling pathways interact to precisely regulate stem cell division for tissue homeostasis. Tctp levels were significantly increased in stem cells and enteroblasts upon tissue damage or activation of the Hippo pathway that promotes regeneration of intestinal epithelium. Stem cells with reduced Tctp levels failed to proliferate during normal tissue homeostasis and regeneration. Mechanistically, Tctp forms a complex with multiple proteins involved in translation and genetically interacts with ribosomal subunits. In addition, Tctp increases both Akt1 protein abundance and phosphorylation in vivo. Altogether, Tctp regulates stem cell proliferation by interacting with key growth regulatory signaling pathways and the translation process in vivo.
View details for DOI 10.1073/pnas.1910850116
View details for PubMedID 31843907
View details for PubMedCentralID PMC6936429
