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Aging Cell. 2017 Dec;16(6):1430-1433. doi: 10.1111/acel.12657. Epub 2017 Sep 17.

In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles.

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Laboratory of Neurosciences, National Institute on Aging, NIH, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Department of Medicine (DIMED), Geriatrics Division, University of Padova, 35128, Padova, Italy.
Department of Medicine, University of Verona, 37129, Verona, Italy.
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD, 21205, USA.
Department of Clinical and Experimental Sciences, Brescia University, 25121, Brescia, Italy.
CEINGE Biotecnologie Avanzate, 80122, Napoli, Italy.


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 (EVs) 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 EVs and in a subpopulation of plasma EVs expressing the neuronal marker L1CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS1 in L1CAM+ EVs in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EVs. 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.


IRS-1; exosomes; extracellular vesicles; leptin receptor; prostate cancer; protein restriction

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