Mechanisms responsible for sub-acute gastrointestinal inflammation in a model of PCOS
Polycystic ovarian syndrome (PCOS) is a condition that affects 7-10% of women in their reproductive years, accounting for roughly 5 million women in the United States. Approximately, 80% of PCOS women suffer from hyperandrogenemia increasing the risk for developing comorbidities, such as obesity, chronic inflammation, increased blood pressure, type II diabetes, insulin resistance, dyslipidemias, and hyperleptinemia. In addition, approximately 42% of PCOS women suffer from gastrointestinal (GI) symptoms, such as abdominal pain, constipation, diarrhea, and/or bloating. Many of these symptoms are associated with sub-acute GI inflammation. Metformin, a common treatment for metabolic dysfunction in PCOS women, causes GI side effects, often resulting in patient non-compliance with treatment. However, the mechanisms that contribute to these symptoms are unknown.
My laboratory focuses on the role of mitochondrial dysfunction in various diseases and mitochodnrial-targeted therapeutics. Therefore, the main questions we seek to answer related to the GI symptoms observed in PCOS are:
- Is colon mitochondrial dysfunction and increased mtROS in HAF rats linked to increased gut dysbiosis and sub-acute GI inflammation?
- Will mitochondrial-targeted antioxidant therapies, such as MitoTEMPO, attenuate these changes?
- Does metformin exacerbate colonic mitochondrial dysfunction increasing gut dysbiosis and inflammation in the HAF rat?
- Will MitoTEMPO improve the effects of metformin?
To answer these questions we will use the the clinical relevant model for PCOS, the hyperandrogenemic female (HAF) rat model, that exhibit similar characteristics as women with PCOS.