Endocrine Abstracts

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS women often have hyperandrogenemia that is associated with adiposity and a worse metabolic profile. However, the depots-specific effect of different white adipose tissues (WAT) in mediating the systemic metabolic dysfunction is not fully understood in PCOS. Therefore, using a well-established mouse model of PCOS, we aim to test the hypothesis that excess androgen will induce systemic metabolic dysfunction and depot-specific WAT derangements.

Methods: Three-week old female mice (C57BL/6N) were implanted with Silastic tubes filled with DHT (8 mg, s.c.) or vehicle (n=6/grp) for 30 days. Weekly body weight (BW, gravimetry), body composition (EchoMRI), retroperitoneal fat (RPF) mass- visceral fat depot and inguinal-gluteal subcutaneous fat (SCF) mass (gravimetry) were assessed. Serum leptin, adiponectin, and non-esterified free fatty acid (NEFA) were measured with ELISA. RPF and SCF, the lipogenesis markers acetyl coA carboxylase (ACC) and fatty acid synthetase (FAS), the lipolytic markers adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) and adipogenesis marker peroxisome proliferator-activated receptor-γ (PPAR-γ) protein levels were assessed by Western blot.

Results: PCOS mice showed significant (P<0.05) increases in BW (1.15-fold), lean mass (1.14-fold), total fat mass (2-fold), RPF mass (2-fold), SCF mass (1.2-fold), leptin (1.2-fold), NEFA (1.3-fold) and lower insulin-sensitizing adipokine adiponectin levels (50%) compared to their vehicle. At the molecular level, in RPF, DHT downregulated ACC and FAS by 50% and 20% respectively. PCOS mice has lower lipolysis in the RPF represented by lower expression of lipases ATGL (50%) and HSL (40%). There was also decrease in the adipogenesis marker PPAR-γ (40%) in RPF in PCOS mice. On the other hand, in SCF ATGL (15%) and HSL (20%) was increased with no changes in FAS and ACC in PCOS mice compared to their vehicle.

Conclusion and significance: Our findings suggest systematic metabolic dysfunction is associated with the depot specific alteration or changes in the markers of adipogenesis and lipogenesis, where both were increased in RPF and decreased in SCF. The observed decrease in SCF could be protective and could help to ameliorate some of the metabolic changes associated with PCOS. Therefore, depot specific targeting may be a possible therapeutic approach for PCOS associated metabolic dysfunction.