Exploring the potential role of ADIPOR2 related to immune microenvironment and metabolism dysfunction in non-alcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a metabolic disorder, and immune-mediated inflammation plays an important role in the progression of the disease. AdipoR2, encoded by ADIPOR2, is closely involved in the pathogenesis of NASH through adiponectin signaling. However, the relationship between ADIPOR2 and the immune microenvironment and metabolic dysfunction in NASH patients remains unexplored. NASH datasets were collected from the public database. ADIPOR2 expression level and its diagnostic value were explored. Then, the relationships among ADIPOR2, the immune microenvironment, and metabolic dysfunction were investigated. ADIPOR2-related genes were identified, a regulatory network was established, and drug sensitivity analysis was conducted. In addition, ADIPOR2 was also verified in clinical samples. ADIPOR2 expression was significantly increased in NASH patients compared to healthy controls and shows better diagnostic value. Immune infiltration analysis found that T cells CD4 memory resting and dendritic cells resting were significantly different in healthy controls versus NASH patients, and ADIPOR2-low versus ADIPOR2-high expression groups. Gene set enrichment analysis and gene set variation analysis showed that metabolism-related pathways (such as HALLMARK_CHOLESTEROL_HOMEOSTASIS, HALLMARK_FATTY_ACID_METABOLISM, and HALLMARK_PEROXISOME) were significantly upregulated in NASH and ADIPOR2-high expression groups. Correlation analysis revealed that ADIPOR2 expression was closely linked to these immune cells and metabolism-related pathways. Then, 16 ADIPOR2-related genes were identified, and the miRNAs-ADIPOR2-TFs regulatory network was constructed. In addition, patients in the ADIPOR2-low expression group showed higher sensitivity to drugs. ADIPOR2 may be a potential diagnostic target and could be related to immune cells and metabolic dysfunction in NASH.