Background; Obesity is one of the most alarming pathological conditions, with an increase in its prevalence globally. In the last decade, it has been associated with fine airborne particles (PM2·5).Methods: Observational study, with an explanatory approach based on Rothman's causal model, through bioinformatic methods.Findings: We propose three new transcriptional signatures in murine adipose tissue with high-confidence protein-protein interaction networks and an FDR of 5%. The sums of transcriptional differences between the group exposed to a high-fat diet (HFD) and PM2·5, in comparison with the control group, were 0·851, 0·265, and -0·047 (p > 0·05). The HFD group increased body mass by 20% with two positive biomarkers of metabolic impact. The group exposed to PM2·5 maintained a similar weight to the control group but exhibited three positive biomarkers. Enriched biological pathways (p < 0·05) included PPAR signaling, small molecule transport, adipogenesis genes, cytokine-cytokine receptor interaction, and HIF-1 signaling. Transcriptional regulation predictions revealed CpG islands and common transcription factors.Interpretation: We propose three new transcriptional signatures: FAT-PM2·5-CEJUS, FAT-PM2·5-UP, and FAT- PM2·5-DN, with expression profiles in adipocytes similar due to HFD or PM2·5, indicating mechanistic interaction. Mice exposed to HFD developed moderately abnormal metabolic obesity, but those exposed to PM2·5 developed severe abnormal metabolism without obesity. HFD is a sufficient cause for developing obesity, and PM2·5 is a component cause of severe abnormal metabolism in obesity. The three signatures exhibit trans-regulation, activating obesogenic pathways, limiting lipid mobilization, reducing adaptive thermogenesis and angiogenesis, and altering vascular tone.Funding: None.Declaration of Interest: We declare no competing interests.