Integrated miRNA_mRNA Analysis Reveals Dysregulated Regulatory Networks in Visceral Adipose Tissue Linked to Obesity and Type 2 Diabetes

Obesity-driven type 2 diabetes (T2D) is characterized by pathological alterations in visceral white adipose tissue (vWAT). While microRNAs (miRNAs) are key post-transcriptional regulators, comprehensive human vWAT profiling across metabolic states remains limited. This study characterized vWAT miRNA expression in lean, obese, and obese+T2D individuals to identify regulatory networks associated with metabolic failure. Deep miRNA sequencing was performed on vWAT samples from a discovery cohort, followed by validation via qPCR in an independent replication cohort. Differentially expressed miRNAs across the three groups were bioinformatically integrated with matched mRNA transcriptomic data to construct functional regulatory modules and identify enriched pathways underlying metabolic impairment. Several miRNAs exhibited robust and reproducible differential expression between obesity and obesity with T2D. Integrated miRNA-mRNA analyses revealed coherent regulatory modules involving inflammation, lipid metabolism, insulin signaling, and iron homeostasis. Specifically, miR-141-3p, miR-200b-3p, miR-15b-3p, miR-12136, and miR-585-3p showed consistent differential expression. Notably, miR-141-3p and miR-200b-3p were markedly upregulated and inversely associated with metabolic stress-related genes, including TF and FBXO32. Several miRNAs correlated with clinical markers of metabolic dysfunction, supporting their biomarker potential. By comparing lean, obese, and diabetic populations, this study provides a comprehensive characterization of the vWAT miRNA landscape and identifies specific miRNA-mRNA regulatory circuits that orchestrate the transition from healthy adiposity to pathological adipose tissue dysfunction. These findings pinpoint novel molecular drivers of type 2 diabetes progression and offer potential targets for therapeutic intervention in metabolic endocrine disorders.