PM2.5 exposure promotes inflammation, disrupts gut microbiota, and exacerbates obesity, AD, and type 2 diabetes by triggering the TLR4 signaling pathway. This leads to leptin resistance, amyloid plaque deposition, and tau hyperphosphorylation, highlighting air pollution as a critical public health concern. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.