Examining mRNA-miRNA Interactions and Gene Expression in Overweight and Obesity

Obesity is characterized by excess adipose tissue, metabolic imbalance, and persistent low-grade inflammation, all of which can affect brain centers and their communication with peripheral organs. The genetic basis of obesity is complex, involving genetics, metagenomics, and gene-environment interactions that impact gene expression. Micro-RNAs (miRNAs) are small, single-stranded, non-coding RNAs that post-transcriptionally regulate the translational rates of target messenger RNAs (mRNAs). Exploring miRNA-mRNA interactions in obesity offers insights into molecular processes, potential biomarkers, and therapeutic targets of this condition. The current study examined the interplay between miRNA and mRNA collected from individuals with overweight and obesity, and normal weight controls. To our knowledge, this is the first experimental attempt to construct a comprehensive dataset of miRNA-mRNA interactions in overweight and obesity. Total RNA, including miRNA, was isolated from venous blood samples collected from 95 participants. Subsequently, 100 ng of RNA from each sample was analyzed using the NanoString quantitative assay. Quantile normalization, the Bayesian-based method Combat, multi-variable linear regression, over-representation, weighted gene correlation network analyses, and functional analyses were conducted. We found an association between IQGAP1 and DAZAP2 genes and miRNA-20-a and miRNA-2113. IQGAP1 and DAZAP2 were associated with insulin signaling and energy metabolism and insulin sensitivity, respectively. We also identified a positive correlation between peripheral cortisol levels and miRNA-548 with alterations in metabolic processes and the immune system. This suggests that miRNA-mRNA interactions in overweight and obesity may impact insulin sensitivity, metabolism, and immunity, providing novel insight into miRNA-mRNA interactions in overweight and obesity. (ClinicalTrials.gov identifier #NCT00824941; https://clinicaltrials.gov/study/NCT00824941).