In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles
Open accessAbstract
Summary: Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age‐associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EV s) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who participated in a randomized trial of one month of PR or control diet. We found increased levels of leptin receptor in the PR group in total plasma EV s and in a subpopulation of plasma EV s expressing the neuronal marker L1 CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS 1 in L1 CAM+ EV s in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EV s. These findings are consistent with improved insulin and leptin sensitivity in response to PR and open a new window for following physiologic responses to dietary interventions in humans.
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Biological properties of extracellular vesicles and their physiological functions
Yáñez‐Mó, M., Siljander, P. R. ‐., Andreu, Z., Bedina Zavec, A., Borràs, F. E., Buzas, E. I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., et al. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.27066 · Cited by 5,926 · see citing works
Talbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871 · see citing works
Impact of intermittent fasting on health and disease processes
Mattson, M. P., Longo, V. D., & Harvie, M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.10.005 · Cited by 1,187 · see citing works
Self-citationCopps, K. D., & White, M. F. (2012) · Diabetologia · doi:10.1007/s00125-012-2644-8 · Cited by 1,017 · cited 2× · see citing works
“…(pY) to serine 312 phosphorylated (pSer312) IRS1 (Y/S IRS1 ratio) was shown to decrease in response to insulin resistance in cell studies (Copps & White, 2012), and we have recently shown that it is significantly decreased in neuronal-enriched EVs of patients with Alzheimer’s disease…”
BackgroundPhysiology of leptin: energy homeostasis, neuroendocrine function and metabolism
Park, H. K., & Ahima, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.004 · Cited by 675 · see citing works
Neuhouser, M. L., Aragaki, A. K., Prentice, R. L., Manson, J. E., Chlebowski, R., Carty, C. L., Ochs-Balcom, H. M., Thomson, C. A., Caan, B. J., Tinker, L. F., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.1546 · Cited by 630 · see citing works
Johnson, J. B., Summer, W., Cutler, R. G., Martin, B., Hyun, D.-H., Dixit, V. D., Pearson, M., Nassar, M., Tellejohan, R., Maudsley, S., et al. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.12.005 · Cited by 604 · see citing works
Self-citationInterventions to slow aging in humans: are we ready?
Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., Curiel, T. J., Cabo, R., Franceschi, C., Gems, D., et al. (2015) · Aging Cell · doi:10.1111/acel.12338 · Cited by 592 · see citing works
Self-citationDecreased consumption of branched-chain amino acids improves metabolic health
Fontana, L., Cummings, N. E., Arriola Apelo, S. I., Neuman, J. C., Kasza, I., Schmidt, B. A., Cava, E., Spelta, F., Tosti, V., Syed, F. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.092 · Cited by 466 · see citing works
Self-citationMustapić, M., Eitan, E., Werner, J. K., Berkowitz, S. T., Lazaropoulos, M. P., Tran, J., Goetzl, E. J., & Kapogiannis, D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00278 · Cited by 453 · see citing works
Self-citationHarvie, M., Wright, C., Pegington, M., McMullan, D., Mitchell, E., Martin, B., Cutler, R. G., Evans, G., Whiteside, S., Maudsley, S., et al. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513000792 · Cited by 431 · see citing works
Self-citationCalorie restriction and cancer prevention: metabolic and molecular mechanisms
Longo, V. D., & Fontana, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.11.004 · Cited by 378 · cited 1× · see citing works
“The risk of many cancers, including prostate cancer, increases with age and being overweight further increases this risk (Longo & Fontana, 2010; Neuhouser et al., 2015).”
BackgroundSelf-citationSixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367 · see citing works
Kapogiannis, D., Boxer, A. L., Schwartz, J. B., Abner, E. L., Biragyn, A., Masharani, U. B., Frassetto, L. A., Petersen, R. C., Miller, B. L., & Goetzl, E. J. (2014) · The FASEB Journal · doi:10.1096/fj.14-262048 · Cited by 345 · see citing works
Self-citationCurrent treatment strategies for inhibiting mTOR in cancer.
Chiarini, F., Evangelisti, C., McCubrey, J., & Martelli, A. (2015) · TIPS - Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.11.004 · Cited by 262 · see citing works
Dietary protein, aging and nutritional geometry
Simpson, S. J., Le Couteur, D. G., Raubenheimer, D., Solon-Biet, S. M., Cooney, G. J., Cogger, V. C., & Fontana, L. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.03.001 · Cited by 169 · see citing works
Self-citationBartke, A. (2008) · Cell Cycle · doi:10.4161/cc.7.21.7012 · Cited by 141 · see citing works
Fontana, L., Adelaiye-Ogala, R. M., Rastelli, A. L., Miles, K. M., Ciamporcero, E. S., Longo, V. D., Nguyen, H. M., Vessella, R. L., & Пили, Р. (2013) · Oncotarget · doi:10.18632/oncotarget.1586 · Cited by 132 · see citing works
Self-citationEffects of Aging on Insulin Secretion
Gumbiner, B., Polonsky, K. S., Beltz, W. F., Wallace, P., Brechtel, G., & Fink, R. I. (1989) · Diabetes · doi:10.2337/diab.38.12.1549 · Cited by 132 · see citing works
Mullins, R. J., Mustapić, M., Goetzl, E. J., & Kapogiannis, D. (2017) · Human Brain Mapping · doi:10.1002/hbm.23494 · Cited by 128 · see citing works
Self-citationBalaskó, M., Soós, S., Székely, M., & Pétervári, E. (2014) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2014.08.006 · Cited by 63 · see citing works
Caloric restriction - A promising anti-cancer approach: From molecular mechanisms to clinical trials
Kopeina, G. S., Senichkin, V. V., & Zhivotovsky, B. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.11.002 · Cited by 57 · see citing works
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Weng, M.-L., Chen, W.-K., Chen, X.-Y., Lu, H., Sun, Z.-R., Yu, Q., Sun, P.-F., Xu, Y.-J., Zhu, M.-M., Jiang, N., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15795-8 · Cited by 242 · see citing works
Retracted
- Authors
- Eitan, E., Tosti, V., Suire, C. N., Cava, E., Berkowitz, S., Bertozzi, B., Raefsky, S. M., Veronese, N., Spangler, R., Spelta, F., Mustapic, M., Kapogiannis, D., Mattson, M. P., & Fontana, L.
- Affiliations
- National Institutes of Health (US)
- Washington University in St. Louis (US)
- University of Padua (IT)
- University of Verona (IT)
- Laboratory of Neurosciences National Institute on Aging, NIH 251 Bayview Boulevard Baltimore MD 21224 USA
- Corresponding author
- Kapogiannis, Dimitrios
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2017-09-17
- Volume
- 16
- Issue
- 6
- Pages
- 1430-1433
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5676054
- OpenAlex
- W2754727539
- Cited by
- 56
- References
- 22
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 6 · 2023: 2 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 12 · 2018: 2 · 2017: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by)
- Funders
- National Institute on Aging
- Longer Life Foundation
- National Center for Research Resources (UL1 RR024992)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- protein restriction, prostate cancer, leptin signaling, insulin signaling, insulin resistance, plasma extracellular vesicles, leptin receptor, L1CAM, IRS-1 phosphorylation, insulin receptor substrate, biomarkers, obesity, metabolic syndrome, hyperleptinemia, aging
- MeSH terms
- Extracellular Vesicles, Energy Metabolism, Humans, Insulin, Male, Middle Aged, Prostatic Neoplasms, Diet, Protein-Restricted, Leptin, Caloric Restriction
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