Unraveling the Mechanism of Immunity and Inflammation Related to Molecular Signatures Crosstalk Among Obesity, T2D, and AD: Insights From Bioinformatics Approaches

Abstract

Individuals with type 2 diabetes (T2D) and obesity have a higher risk of developing Alzheimer disease (AD), and increasing evidence indicates a link between impaired immune signaling pathways and the development of AD. However, the shared cellular mechanisms and molecular signatures among these 3 diseases remain unknown. The purpose of this study was to uncover similar molecular markers and pathways involved in obesity, T2D, and AD using bioinformatics and a network biology approach. First, we investigated the 3 RNA sequencing (RNA-seq) gene expression data sets and determined 224 commonly shared differentially expressed genes (DEGs) from obesity, T2D, and AD diseases. Gene ontology and pathway enrichment analyses revealed that mutual DEGs were mainly enriched with immune and inflammatory signaling pathways. In addition, we constructed a protein-protein interactions network for finding hub genes, which have not previously been identified as playing a critical role in these 3 diseases. Furthermore, the transcriptional factors and protein kinases regulating commonly shared DEGs among obesity, T2D, and AD were also identified. Finally, we suggested potential drug candidates as possible therapeutic interventions for 3 diseases. The results of this bioinformatics analysis provided a new understanding of the potential links between obesity, T2D, and AD pathologies.

The Perfect Cup? Coffee-Derived Polyphenols and Their Roles in Mitigating Factors Affecting Type 2 Diabetes Pathogenesis

“…This results in excess triacylglycerols and, eventually, obesity [ 82 ], which is linked to the excess production of pro-inflammatory cytokines and the activation of apoptotic pathways [ 83 ]. For example, the NF-κB pathway is initiated, yielding the production of many pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6, thus perpetuating the problems of T2D [ 46 , 83 , 84 ] ( Figure 2 ).…”

“…However, chronic overnutrition and a positive energy balance, which is consistent with the lifestyle of most people with type 2 diabetes, promotes increased glucose disposal in adipocytes in which, after meeting the energy demand of the adipocyte, will ultimately be converted to and stored as fat [81]. This results in excess triacylglycerols and, eventually, obesity [82], which is linked to the excess production of pro-inflammatory cytokines and the activation of apoptotic pathways [83]. For example, the NF-κB pathway is initiated, yielding the production of many pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6, thus perpetuating the problems of T2D [46,83,84] (Figure 2).…”

Quantitative susceptibility mapping for iron monitoring of multiple subcortical nuclei in type 2 diabetes mellitus: a systematic review and meta-analysis

“…Among these, the implications of diabetes on neurological health have attracted considerable attention ( 5 ). The intricate relationship between diabetes and neurological disorders has sparked extensive research aimed at elucidating the underlying mechanisms and potential biomarkers associated with this complex interaction ( 6 ).…”

The Active Ingredient Catalpol in Rehmannia glutinosa Reduces Blood Glucose in Diabetic Rats via the AMPK Pathway

“…[14][15][16] In addition, molecular pathways have a critical role in the development and complications of T2DM. [17][18][19] Therapeutic studies for T2DM are increasingly focusing on the regulation of molecular pathways to find new therapeutic targets. Among them, the signaling pathway of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) has attracted a lot of attention, and AMPK plays an important role in insulin resistance, β-cell function, and complications of T2DM.…”