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

• Published in: Oncotarget 2015-10, Vol.6 (30), p.29818-29832
• Main Authors: Rahimi, Mehran, Vinciguerra, Manlio, Daghighi, Mojtaba, Özcan, Behiye, Akbarkhanzadeh, Vishtaseb, Sheedfar, Fareeba, Amini, Marzyeh, Mazza, Tommaso, Pazienza, Valerio, Motazacker, Mahdi M, Mahmoudi, Morteza, De Rooij, Felix W M, Sijbrands, Eric, Peppelenbosch, Maikel P, Rezaee, Farhad
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - blood; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adipose Tissue - metabolism; Adult; Aged; Analysis of Variance; Apolipoprotein A-I - blood; Apolipoprotein A-I - genetics; Apolipoprotein A-I - metabolism; Apoptosis Regulatory Proteins - blood; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Profiling; Gene Expression Regulation - genetics; Humans; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; Male; Middle Aged; Nerve Growth Factors - blood; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Neurons - metabolism; Obesity - physiopathology; Pancreas - metabolism; Proto-Oncogene Proteins c-vav - blood; Proto-Oncogene Proteins c-vav - genetics; Proto-Oncogene Proteins c-vav - metabolism; Research Paper; Reverse Transcriptase Polymerase Chain Reaction; Synaptotagmins - blood; Synaptotagmins - genetics; Synaptotagmins - metabolism
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.4904

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.