Neuron stress-related genes serve as new biomarkers in hypothalamic tissue following high fat diet

Objective: Energy homeostasis is modulated by the hypothalamic is essential for obesity progression, however, the gene expression profiling remains to be fully understood.

Methods: GEO datasets were downloaded from the GEO website and analyzed by the R packages to obtain the DEGs. And, the WGCNA analysis and PPI networks of co-expressed DEGs were designed using STRING to get key genes. In addition, the single-cell sequencing datasets and GTEx database were utilized to receive the neuron-stress genes from the key genes. Further, high-fat diet (HFD)-induced hypothalamic tissue of mice was used as an animal model to validate the mRNA up-regulation of neuron-stress genes. In addition, the Bmi1 gene was identified as a hub gene through the LASSO model and nomogram analysis. Western blot confirmed the high expression of Bmi1 in hypothalamic tissue of HFD mice and PA-stimulated microglia. Immunofluorescence staining showed that HFD induced the activation of microglia and the expression of Bmi1 in hypothalamic tissue.

Results: We found that six genes (Sacm1l, Junb, Bmi1, Erbb4, Dkc1, and Suv39h1) are neuron stress-related genes and increased in the HFD-induced mice obesity model, Bmi1gene was identified as a key genes that can reflect the pathophysiology of obesity.

Conclusions: Our research depicted a comprehensive activation map of cell abnormality in the obese hypothalamus and Bim1 may be a diagnostic marker in the clinic, which provides a new perspective and basis for investigating the pathogenesis of obesity.