Aldehyde oxidase is induced during adipogenesis and is more abundant in visceral when compared to subcutaneous adipose tissue

Background: Aldehyde oxidase (AOX1), an enzyme mainly expressed by hepatocytes, is involved in the catabolism and activation of various drugs, in retinoic acid, ethanol and oxygen radical metabolism. Hyperglycemia stimulates the induction of reactive oxygen species (ROS) in adipocytes that are associated with insulin resistance and an inflammatory response. Because AOX1 is involved in hepatic ROS metabolism, the expression of this enzyme was analysed in primary human adipocytes and subcutaneous and visceral adipose tissue.

Results: Adipose tissue was obtained from patients undergoing human liver resections and was used to isolate RNA or protein. AOX1 mRNA was amplified from subcutaneous (sc) and visceral (vs) fat isolated from 5 different donors and was more abundant in vs. adipose tissue. Actin related protein 2 was used for normalisation of the mRNA data because the common housekeeping gene β-actin was also lower in sc adipose tissue whereas porphobilinogen deaminase (PBGD) was highly variable. Immunoblot analysis was performed and AOX1 protein was more abundant in vs. fat. AOX1 was not detected by immunohistochemistry in vs. adipose tissue most likely because of the lower sensitivity of this method. Therefore, purified human adipocytes were analysed by immunoblot and AOX1 was detected in these cells. In addition, preadipocytes and mature adipocytes from 3 different donors were used for immunoblot and AOX1 was found strongly induced in mature cells. 3T3-L1 preadipocytes were differentiated in-vitro and, in contrast to primary human adipocytes, AOX1 is highly expressed in non-differentiated cells and downregulated in differentiated adipocytes.

Conclusion: AOX1 is induced in mature human adipocytes and is higher expressed in visceral fat when compared to subcutaneous adipose tissue. Future studies have to clarify the role of AOX1 in ROS metabolism and insulin resistance. In addition these data indicate that adipose tissue may have a role in drug metabolism.