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Bell's palsy is the most common form of facial nerve palsy. This study aimed to explore the pathogenesis of Bell's palsy by investigating the effect of cold-stimulated adipocyte supernatant on adhesion molecule expression in Schwann cell line. Schwann cells were cultured in regular or adipocyte-conditioned medium and analyzed using RNA sequencing. The mRNA expression of Schwann cell adhesion molecules melanoma cell adhesion molecule (MCAM), protocadherin 9 (PCDH9), and intercellular cell adhesion molecule 1 (ICAM1) was determined using real-time reverse-transcription polymerase chain reaction. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted. Compared with Schwann cells in 37 °C, the expression of MCAM, PCDH9, and ICAM1 was downregulated in Schwann cells treated with cold-stimulated adipocyte supernatant compared with Schwann cells in 37 °C. Adipocytes subjected to cold exposure may weaken the adhesion capacity of Schwann cells and disrupt the local homeostasis of Schwann cell–axon interactions by affecting the expression of MCAM, PCDH9, and ICAM1, ultimately leading to the development of demyelinating lesions.