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

Erez Eitan, Valeria Tosti, Caitlin N. Suire, Edda Cava, Sean Berkowitz, Beatrice Bertozzi, Sophia M. Raefsky, Nicola Veronese, Ryan Spangler, Francesco Spelta, Maja Mustapic, Dimitrios Kapogiannis, Mark P. Mattson, Luigi Fontana

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1430-1433
Number of pages4
JournalAging Cell
Volume16
Issue number6
DOIs
StatePublished - Dec 2017

Keywords

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

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