Browning of Aldosterone‐Producing Adenoma Adjacent Adipose Tissue Involved in Aldosterone Synthesis Regulation

ABSTRACT Aldosterone‐producing adenoma (APA) is a benign adrenal tumor that results in persistent autonomous aldosterone secretion. Current studies indicate a close association between adjacent adipose tissue and tumor progression. Here, we preliminarily explore the association between APA and adjacent adipocytes. The results revealed that APA‐adjacent adipose tissue exhibited a browning phenotype, evidenced by smaller adipocytes, higher expression of uncoupling protein 1 (UCP1) as detected by immunohistochemistry and immunofluorescence, and upregulated UCP1 and peroxisome proliferator‐activated receptor gamma co‐activator‐1 alpha ( PGC1α ) mRNA levels. The untargeted lipidomics also showed evidence of browning. Furthermore, higher expression of aldehyde dehydrogenase 1, family member A2 (ALDH1A2) and elevated contents of retinoic acid (RA) which promoted browning of adjacent adipocytes were observed in APA. Lactate levels were also significantly higher in APA‐adjacent adipose tissue, which enhanced the aldosterone synthase (CYP11B2) expression and aldosterone secretion of H295R cells. In conclusion, these data indicate that there might be an interaction between APA and adjacent adipose tissue, and RA and lactate may serve as mediators of this interaction. These results provide insights into the role of adipose tissue in the APA microenvironment.