Endocrine Abstracts

Background

Obesity is closely associated with impaired adipose tissue function. Although bariatric surgery is the treatment of choice for severe obesity and its related conditions, there are conflicting data on the reversal of adipose tissue dysfunction after surgery-induced weight loss. We hypothesise that local steroid hormone availability influences fat deposition or mobilisation and that these changes track with weight loss improvements, because plasma steroid concentrations are altered in obesity. For the first time, we characterise markers of visceral (VAT) and subcutaneous (SAT) adipose tissue function including fourteen in situ endogenous steroids and their change after surgery-induced weight loss in humans.

Methods

Institutional approval and consent were obtained. SAT and VAT were collected in men (n = 15) and women (n = 23) before and after sleeve gastrectomy. A validated liquid chromatography-tandem mass spectrometry method was developed to determine steroid hormone amounts in adipose tissue. Principal component analysis was performed to establish global trends related to the impact of depot, sex, and time after surgery. Repeated mixed-models were used to investigate associations of steroid hormones measured by ESI-LC-MS/MS (oestrone, oestradiol, androstenedione, testosterone, 5α-DHT, 5α-androstanedione, DHEA, cortisone, cortisol, 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, 11-ketotestosterone, and 11-ketoDHT) and of several steroid-converting enzyme transcripts.

Results

Post-surgery samples were obtained on average 26 ± 6 months after baseline. Participants had a preoperative mean BMI of 53 kg/m² (range 38–65). VAT had higher amounts of glucocorticoids, androgens, and 11-oxy-androgens. Oestrogens were higher in SAT. After weight loss, testosterone and 5α-dihydrotestosterone adipose tissue amounts were increased only in men (P < 0.05). Oestrogen amounts were decreased in both sexes (P < 0.05). Aromatase expression was higher in men before weight loss and then decreased in both sexes (P < 0.01). Expression of DHRS11, an enzyme with oestrogenic 17β-HSD activity, was decreased in women after weight loss (P < 0.01). AKR1C2, AKR1C3, HSD11B1, SRD5A1 and SRD5A3 expression also decreased significantly in both fat depots (P < 0.05), but not cortisol nor cortisone amounts. The waist-to-hip ratio was positively associated with concentrations of testosterone, 5α-DHT, 11β-hydroxyandrostenedione, 11β-hydroxytestosterone, androstenedione and 11-ketoDHT in VAT, and with testosterone and 11β-hydroxytestosterone in SAT (P < 0.05).

Conclusions

This is the first study reporting extensive intra-adipose steroid profiling before and after weight loss in a sample of men and women with severe obesity, including newly characterised 11-oxy-androgens. We found that intra-adipose oestrogen amounts decreased, active androgens increased, and 11-oxy-androgens were stable following bariatric surgery. None of the steroids studied were directly associated with the degree of weight loss, suggesting other biological mechanisms at play.