Unraveling Obesity: A Five-Year Integrative Review of Transcriptomic Data

Abstract

Omics approaches have advanced insight into molecular mechanisms of human obesity. We reviewed transcriptomic studies published between January 2020 and June 2025 that used human tissues or human cell lines and applied high-throughput RNA methods. Across these works three convergent themes emerged: (1) immune–inflammatory activation—particularly interferon-stimulated and innate immune signatures—linked to insulin resistance and visceral adiposity; (2) dysregulation of lipid and energy-metabolism pathways, including reduced lipolysis and β-oxidation in adipose tissue and liver; and (3) epigenetic and post-transcriptional regulation mediated by DNA methylation, histone modification, long noncoding RNAs, microRNAs and circular RNAs. Multi-omics integration (transcriptome with proteome, metabolome and microbiome) improved mechanistic interpretation and biomarker discovery but was limited by cohort heterogeneity and technical variation. We conclude that standardized, integrative multi-omics analyses in well-characterized, longitudinal human cohorts are required to translate molecular signatures into robust biomarkers and personalized therapeutic strategies for obesity.