ODP001 AKR1C2 Activity in Abdominal Adipose Tissue of Women with or without Excess Visceral Adiposity

BACKGROUND: Adipose tissue is known to play an active role in androgen turnover, as illustrated by the presence of enzymes of the aldo-keto reductase 1C family such as AKR1C2 and AKR1C3, respectively coding for 3α-hydroxysteroid dehydrogenase type 3 and 17β-hydroxysteroid dehydrogenase type 5. Our group demonstrated that these enzymes are mainly expressed in mature adipocytes and that in women, trunk fat percentage is positively associated with adipose tissue mRNA abundance of both AKR1C2 and AKR1C3. In this context, our aim was to assess whether abdominal adipose tissue activity of AKR1C2 relates to excess visceral adiposity index (VAI) in women. METHODS: AKR1C2 activity was measured in visceral (VAT) and subcutaneous adipose tissue (SAT) of 31 women (age: 39 ± 7; BMI: 51 ± 6) undergoing bariatric surgery. Adipose tissue homogenate activity was measured by fluorimetry in a 12-hour kinetic experiment using the chemical compound cumberone, a competitive substrate in the inactivation of 5a-dihydrotestosterone to 3α-androstanediol by AKR1C2. Visceral adipose tissue excess was quantified using the previously published VAI equation and using the age-specific cut-offs for women, who were categorized into either high VAI or low VAI. Other markers of adipose tissue dysfunction included diacylglycerol acyltransferase 2 (DGAT2) and glutathione peroxidase 3 (GPX3) mRNA abundance, adipocyte size and pericellular fibrosis. RESULTS: Our technique allowed us to detect significant AKR1C2 activity in SAT (13.5±5.7 fluorescence units (FU)/min) and VAT (8.3±4.8 FU/min). Using the VAI equation, we identified 18 women with high VAI and 13 with low VAI. Women with high VAI were characterized by significantly higher VAT AKR1C2 activity when compared to women with low VAI (9.5 ± 4.4 vs. 6.4± 3.6 FU/min, p<0. 05). AKR1C2 mRNA abundance in either VAT or SAT was not significantly different as a function of VAI. Women with high VAI also had larger VAT adipocyte diameter and lower mRNA abundance of GPX3 in both adipose tissue depots compared to women with low VAI (p<0. 05 for all). No differences were seen in DGAT2 mRNA abundance, pericellular fibrosis or SAT adipocyte diameter as a function of VAI. CONCLUSION: In women with severe obesity, excess visceral adiposity as indicated by a high VAI, is associated with higher AKR1C2 activity in VAT only. Similarly, adipose tissues of women with high VAI displayed features of adipose tissue dysfunction such as increased VAT adipocyte diameter and decreased GPX3expression in comparison to women with low VAI. Taken together our results confirm the link between adipose AKR1C2 and excess visceral adiposity. Presentation: No date and time listed