Calorie Restriction Ameliorates Cardiometabolic Risk Factors in a Rat Model of Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women. PCOS is diagnosed by the combination of excess of androgens, oligo-/anovulation, and polycystic ovarian morphology. Women with PCOS suffer from a high prevalence of cardiometabolic complications such as insulin resistance (IR), obesity, and cardiovascular disease. We have previously reported that hyperandrogenemia in a rodent model of PCOS is associated with obesity, IR, and low levels of plasma adiponectin, an insulin sensitizing hormone. However, the impact of calorie restriction (CR) via pair-feeding (PF) on these obesity-associated metabolic complications remains unclear and is the focus of this study. Hypothesis: We hypothesized that treating obesity via CR will ameliorate the cardiometabolic complications observed in a rat model of PCOS. Methods: To induce PCOS, four-week-old female Sprague-Dawley rats were implanted subcutaneously with dihydrotestosterone (DHT, 8.0 mg) or empty silastic tubes (PBO) for 90 days (n=10/grp). DHT-treated rats were further randomly assigned to either a pair-feeding (DHT-PF) or ad libitum diet starting at 4 weeks of age. All animals were maintained on a standard chow diet. Bi-weekly body weight (BW, gravimetry), fat mass and lean mass (EchoMRI) were assessed, and body mass index (BMI) was calculated by the equation BMI = weight (kg)/ length (m2). Plasma insulin, leptin, adiponectin and IR (HOMA-IR) were measured by ELISA. Low-density lipoprotein (LDL) levels were measured using VetAxcel. Statistical analysis was conducted using two-way ANOVA. Results: Hyperandrogenemia induced by DHT causes an increase in BW (26%), fat mass (24%), and lean mass (27%) compared with the PBO group. These effects of DHT were attenuated by CR, which reduced BW, fat mass, and lean mass by 7%, 41%, and 4% (p0.05). HOMA-IR was significantly increased by DHT compared to PBO (11.5 ± 9.4 vs 6.4 ± 5.1) and decreased by CR compared to DHT-treated rats (11.5 ± 9 vs 4.5 ± 3; p< 0.05). Conclusion: In PCOS, excess androgens are associated with cardiometabolic complications. Our data demonstrate that CR via pair-feeding ameliorates the obesity-associated metabolic complications, such as IR, hyperleptinemia, and hypoadiponectinemia observed in the hyperandrogenic rat model of PCOS. These findings suggest that obesity drives the cardiometabolic complication in PCOS and that weight reduction via CR may be beneficial in mitigating these complications. Funding: This research was supported funding from National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI) grants R01HL171494 (L.L.Y.C.), R01HL144847 (D.G.R.) and T32 HL105324, National Institute of General Medical Sciences grants P20GM121334 (L.L.Y.C., S.R., and D.G.R.), P50MD017338 (L.L.Y.C.), P30GM149404 (S.R.) and American Diabetes Association 1-26-PDF-0678 (M.A.E). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.