Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

Mehran Rahimi, Manlio Vinciguerra, Mojtaba Daghighi, Behiye özcan, Vishtaseb Akbarkhanzadeh, Fareeba Sheedfar, Marzyeh Amini, Tommaso Mazza, Valerio Pazienza, Mahdi M. Motazacker, Morteza Mahmoudi, Felix W M De Rooij, Eric Sijbrands, Maikel P. Peppelenbosch, Farhad Rezaee

Research output: Contribution to journalArticle

Abstract

Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

Original languageEnglish
Pages (from-to)29818-29832
Number of pages15
JournalOncotarget
Volume6
Issue number30
DOIs
Publication statusPublished - 2015

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Keywords

  • Age-related diabetes neuropathy
  • Aging
  • Diabetes
  • Obesity
  • Pancreas

ASJC Scopus subject areas

  • Oncology

Cite this

Rahimi, M., Vinciguerra, M., Daghighi, M., özcan, B., Akbarkhanzadeh, V., Sheedfar, F., Amini, M., Mazza, T., Pazienza, V., Motazacker, M. M., Mahmoudi, M., De Rooij, F. W. M., Sijbrands, E., Peppelenbosch, M. P., & Rezaee, F. (2015). Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans. Oncotarget, 6(30), 29818-29832. https://doi.org/10.18632/oncotarget.4904