RESUMEN
Obesity is currently one of the most alarming pathological conditions due to the progressive increase in its prevalence. In the last decade, it has been associated with fine particulate matter suspended in the air (PM2.5). The purpose of this study was to explore the mechanistic interaction of PM2.5 with a high-fat diet (HFD) through the differential regulation of transcriptional signatures, aiming to identify the association of these particles with metabolically abnormal obesity. The research design was observational, using bioinformatic methods and an explanatory approach based on Rothman's causal model. We propose three new transcriptional signatures in murine adipose tissue. The sum of transcriptional differences between the group exposed to an HFD and PM2.5, compared to 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. We propose three new transcriptional signatures: FAT-PM2.5-CEJUS, FAT-PM2.5-UP, and FAT-PM2.5-DN, whose transcriptional regulation profile in adipocytes was statistically similar by dietary intake and HFD and exposure to PM2.5 in mice; suggesting a mechanistic interaction between both factors. However, HFD-exposed murines developed moderate metabolically abnormal obesity, and PM2.5-exposed murines developed severe abnormal metabolism without obesity. Therefore, in Rothman's terms, it is concluded that HFD is a sufficient cause of the development of obesity, and PM2.5 is a component cause of severe abnormal metabolism of obesity. These signatures would be integrated into a systemic biological process that would induce transcriptional regulation in trans, activating obesogenic biological pathways, restricting lipid mobilization pathways, decreasing adaptive thermogenesis and angiogenesis, and altering vascular tone thus inducing a severe metabolically abnormal obesity.
RESUMEN
Environmental factors, including pollutants and lifestyle, constitute a significant role in severe, chronic pathologies with an essential societal, economic burden. The measurement of all environmental exposures and assessing their correlation with effects on individual health is defined as the exposome, which interacts with our unique characteristics such as genetics, physiology, and epigenetics. Epigenetics investigates modifications in the expression of genes that do not depend on the underlying DNA sequence. Some studies have confirmed that environmental factors may promote disease in individuals or subsequent progeny through epigenetic alterations. Variations in the epigenetic machinery cause a spectrum of different disorders since these mechanisms are more sensitive to the environment than the genome, due to the inherent reversible nature of the epigenetic landscape. Several epigenetic mechanisms, including modifications in DNA (e.g., methylation), histones, and noncoding RNAs can change genome expression under the exogenous influence. Notably, the role of long noncoding RNAs in epigenetic processes has not been well explored in the context of exposome-induced tumorigenesis. In the present review, our scope is to provide relevant evidence indicating that epigenetic alterations mediate those detrimental effects caused by exposure to environmental toxicants, focusing mainly on a multi-step regulation by diverse noncoding RNAs subtypes.
