Open AccessIn a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles
Author(s) -
Eitan Erez,
Tosti Valeria,
Suire Caitlin N.,
Cava Edda,
Berkowitz Sean,
Bertozzi Beatrice,
Raefsky Sophia M.,
Veronese Nicola,
Spangler Ryan,
Spelta Francesco,
Mustapic Maja,
Kapogiannis Dimitrios,
Mattson Mark P.,
Fontana Luigi
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12657
Subject(s) - leptin , prostate cancer , endocrinology , medicine , biology , extracellular vesicle , insulin , insulin resistance , insulin receptor , cancer , cancer research , obesity , microrna , biochemistry , microvesicles , gene
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.