Prenatally androgenised (PA) sheep are a clinically realistic model of polycystic ovary syndrome (PCOS). They have dysfunctional subcutaneous adipose tissue (SAT) with reduced adipogenesis in adolescence and enlarged adipocytes with increased inflammation in adulthood. We hypothesised that analysis of SAT in young adults, after adipogenesis is complete but before inflammation is apparent, would give insights into the evolution of adipose tissue dysfunction. Pregnant sheep were treated intramuscularly with 100 mg testosterone propionate or vehicle control (C) twice weekly from day 62-102 of gestation. Weight-matched female offspring (PA = 10; C = 10) were studied up to 22 months of age. Glucose tolerance testing was performed, and at sacrifice SAT was fixed for histological analysis and frozen for RNA sequencing (RNAseq) and gene expression analysis. There was no difference in the average size of SAT adipocytes between PA and C young adults. There were no differences in the expression of the adipogenesis markers PPARG, CEBPA and CEBPB, or the inflammatory markers TNF and IL6, although PA sheep were already hyperinsulinaemic. RNAseq identified 792 potentially differentially expressed (P < 0.05) genes in PA sheep SAT (406 upregulated; 386 downregulated). Ingenuity Pathway Analysis highlighted upregulation of fibrotic pathways in the SAT of PA sheep. POSTN, associated with tissue fibrosis, and COL1A1, COL1A2 and COL3A1 were significantly elevated, and histochemistry showed significantly increased SAT fibrosis in PA sheep. Early fibrotic changes in SAT occur before inflammatory gene expression in PA sheep. A fibrotic barrier to healthy adipocyte expansion may have a mechanistic role in the development of inflammation in PCOS.

Peripartum cardiomyopathy (PPCM) complicated by pulmonary arterial hypertension (PAH) is an uncommon and high-risk condition that presents significant anesthetic and obstetric challenges. This case report contributes to the limited literature by describing the successful anesthetic management of a parturient with severe cardiac dysfunction and PAH, emphasizing the importance of a multidisciplinary approach. A 30-year-old pregnant woman with newly diagnosed dilated cardiomyopathy of unknown etiology and PAH was admitted for elective cesarean delivery. The diagnosis was established in the second trimester following symptoms of dyspnea at rest. Transthoracic echocardiography revealed severe left ventricular systolic dysfunction and elevated pulmonary artery pressures. A combined spinal-epidural technique was selected to allow for gradual onset of anesthesia and tight hemodynamic control. The patient was managed in a multidisciplinary setting involving anesthesiology, cardiology, obstetrics, and intensive care. Intraoperative and postoperative periods were uneventful, with no signs of pulmonary edema or right ventricular failure. The patient was discharged in stable condition on postoperative day 7. This case highlights the critical importance of individualized anesthetic planning and collaborative multidisciplinary care in the management of high-risk obstetric patients with PPCM and PAH. Early diagnosis, careful monitoring, and tailored interventions are key to optimizing maternal and neonatal outcomes in such complex scenarios.

Adipose tissue dysfunction is one of the features of Polycystic Ovary Syndrome (PCOS) with dysregulated adipogenesis, altered functional pathways and increased inflammation. It is increasingly clear that there are also male correlates of the hormonal and metabolic features of PCOS. We hypothesised that the effects of adipose tissue dysfunction are not sex-specific but rather fat depot-specific and independent of obesity. We used a clinically realistic ovine model of PCOS where pregnant sheep are injected with 100 mg of testosterone propionate twice weekly from day 62 to day 102 of gestation. We studied control and prenatally androgenised (PA) female and male offspring during adolescence and weight-matched control and PA female sheep during adulthood. We examined subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and in adult female sheep bone marrow adipose tissue (BMAT). Adipogenesis related gene expression in SAT was similar in adolescent female and male controls and the reduction in adipogenesis related gene expression by PA in female adipose tissue was not observed in males. Differences in expression of genes associated with adipose tissue function in adolescence in SAT driven by PA were found in both sexes. In adulthood, the changes seen in adolescent females were absent or reversed but there was an increase in inflammatory markers that was weight independent. In addition, BMAT showed increased inflammatory markers. Adipose dysfunction evolves with time and is focussed on SAT rather than VAT and is generally sex-specific although there are also effects of prenatal androgenisation on male SAT. In female adults, the inflammation seen in SAT is also present in BMAT and the development of blood cells in an inflammatory environment may have systemic implications.

Excessive expansion of adipose tissue in obesity typically leads to overflow and accumulation of lipids in other tissues, causing fatty liver disease and atherosclerosis. The intracellular protein, phosphoprotein enriched in astrocytes (PEA)-15 has been linked to metabolic disease but its role in lipid storage has not been examined. To delineate the role of PEA-15 in adipose tissue, we placed PEA-15-/- mice on a high fat diet. These mice developed increased body weight and greater white adipose tissue expansion compared to high fat diet-fed wild type mice. This was due to increased adipocyte cell size in PEA-15-/- mice consistent with greater lipid storage capacity. Surprisingly, PEA-15-/- mice exhibited improvements in whole body insulin sensitivity, lower hepatic weight and decreased serum triglycerides indicating a protective phenotype. To determine effects on atherosclerosis, PEA-15-/- mice were crossed with the ApoE-/- mice on a high fat diet. Strikingly, these mice were protected from atherosclerosis and had less hepatic lipid accumulation despite increased adiposity. Therefore, we reveal for the first time that PEA-15 plays a novel role in regulating the expansion of adipose tissue. Decreasing PEA-15 expression increases the sequestering of lipids in adipose tissue, protecting other tissues in obesity, thereby improving metabolic health.