Nutritional Triggers of PCOS and NAFLD: A Comparative Analysis of Diets in Female C57BL/6J Mice

ObjectiveObesity is a key factor in the development of Polycystic Ovary Syndrome (PCOS) and Non- alcoholic fatty liver disease (NAFLD). Its relationship with reproductive health and metabolic disorders remains an area of interest. Here we aimed to study the effects of two different obesogenic diets in female C57BL/6J mice on their metabolic and reproductive function. MethodsFemale C57BL/6J mice were fed high-fat high-sugar (HFHS) (45% fat and 10% sugar) diet and High fat diet (60% fat) for 21 weeks to investigate the effects on metabolic health and reproductive health. Mice were assessed for body weight, abdominal circumference, glucose tolerance (OGTT) and estrous cyclicity. At the end of the study biochemical analysis was done on isolated serum and, histological assessment of organs including liver and ovarian tissue was done to score for cystic follicle development and steatosis respectively. ResultsMice on the HFHS diet did not gain weight but developed dyslipidaemia, abnormal liver enzyme levels and severe hepatic steatosis. They did not show impaired glucose tolerance and did not develop any PCOS-like ovarian morphology indicating hepatic metabolic disturbances without significant impact on reproductive health. In contrast, mice on the 60% high-fat diet (HFD) showed marginal increase in body weight and developed altered estrous cyclicity and PCOS-like ovarian morphology. They also exhibited impaired glucose tolerance and insulin resistance, confirming a metabolic disturbance associated with PCOS. These mice did not develop significant liver fibrosis, suggesting a more specific impact on the ovaries and glucose metabolism. Our findings suggest that diet composition plays a crucial role in determining the specific metabolic and reproductive outcomes in obesity-related disorders in females.