Lobato Sagrario, Castillo-Granada A Lourdes, Bucio-Pacheco Marcos, Salomón-Soto Víctor Manuel, Álvarez-Valenzuela Ramiro, Meza-Inostroza Perla Margarita, Villegas-Vizcaíno Raúl
Departamento de Investigación en Salud, Servicios de Salud del Estado de Puebla, 15 South Street 302, Puebla, Mexico.
Promoción y Educación para la Salud, Universidad Abierta y a Distancia de México. Universidad Avenue 1200, 1st Floor, quadrant 1-2, Xoco, Benito Juarez, 03330, Mexico City, Mexico.
Heliyon. 2024 Apr 3;10(7):e28936. doi: 10.1016/j.heliyon.2024.e28936. eCollection 2024 Apr 15.
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 (PM). The purpose of this study was to explore the mechanistic interaction of PM 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 PM, 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 PM 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-PM-CEJUS, FAT-PM-UP, and FAT-PM-DN, whose transcriptional regulation profile in adipocytes was statistically similar by dietary intake and HFD and exposure to PM in mice; suggesting a mechanistic interaction between both factors. However, HFD-exposed murines developed moderate metabolically abnormal obesity, and PM-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 PM 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.
肥胖症目前是最令人担忧的病理状况之一，因其患病率呈逐步上升趋势。在过去十年中，它一直与空气中悬浮的细颗粒物（PM）有关。本研究的目的是通过转录特征的差异调节来探索PM与高脂饮食（HFD）之间的机制相互作用，旨在确定这些颗粒与代谢异常肥胖症的关联。研究设计为观察性研究，采用生物信息学方法和基于罗斯曼因果模型的解释性方法。我们在小鼠脂肪组织中提出了三个新的转录特征。与对照组相比，暴露于HFD和PM的组之间转录差异的总和分别为0.851、0.265和-0.047（p>0.05）。HFD组体重增加了20%，有两个代谢影响的阳性生物标志物。暴露于PM的组体重与对照组相似，但表现出三个阳性生物标志物。富集的生物途径（p<0.05）包括PPAR信号传导、小分子转运、脂肪生成基因、细胞因子-细胞因子受体相互作用和HIF-1信号传导。转录调控预测揭示了CpG岛和常见转录因子。我们提出了三个新的转录特征：FAT-PM-CEJUS、FAT-PM-UP和FAT-PM-DN，其在脂肪细胞中的转录调控谱在小鼠饮食摄入、HFD以及暴露于PM方面在统计学上相似；这表明这两个因素之间存在机制相互作用。然而，暴露于HFD的小鼠出现了中度代谢异常肥胖症，而暴露于PM的小鼠出现了严重的代谢异常但无肥胖症。因此，用罗斯曼的话说，得出的结论是HFD是肥胖症发生的充分原因，而PM是肥胖症严重代谢异常的一个组成原因。这些特征将整合到一个系统性生物过程中，该过程将诱导反式转录调控，激活致肥胖生物途径，限制脂质动员途径，减少适应性产热和血管生成，并改变血管张力，从而导致严重的代谢异常肥胖症。
