Metabolic Dysfunction-Associated Steatotic Liver Disease and Polycystic Ovary Syndrome: A Complex Interplay

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  Figure 1. Newly established disease criteria for the diagnosis of MASLD and the Rotterdam criteria for the diagnosis of PCOS. MASLD is defined as hepatic steatosis combined with at least one out of five CMRF: (1) BMI ≥ 25 kg/m2 (≥23 kg/ m2 for Asians) or WC > 94 cm for males and >80 cm for females or ethnicity adjusted; (2) fasting serum glucose ≥ 5.6 mmol/L (100 mg/dL) or 2-h post-load glucose levels ≥ 7.8 mmol/L (≥140 mg/dL) or glycated hemoglobin ≥ 5.7% (39 mmol/L) or type 2 diabetes or treatment for type 2 diabetes; (3) blood pressure ≥ 130/85 mmHg or specific antihypertensive drug treatment; (4) plasma triglycerides ≥ 1.70 mmol/L (150 mg/dL) or lipid-lowering treatment; and (5) plasma high-density lipoprotein (HDL) cholesterol ≤ 1.0 mmol/L (40 mg/dL) for males and ≤1.3 mmol/L (50 mg/dL) for females or lipid-lowering treatment. Patients with SLD and at least one out of five CMRF are categorized as having MASLD when there are no other causes of steatosis present. According to the Rotterdam consensus, PCOS is defined by the presence of two out of three of the following criteria: oligo/amenorrhea or anovulation, hyperandrogenism (clinical and/or biochemical) and polycystic ovaries (≥12…

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  Figure 2. Schematic presentation of the pathophysiological mechanisms correlating MASLD with PCOS. Insulin resistance disturbs fatty acid and hepatic lipid metabolism, leading to a chronic low-grade inflammatory state and fibrosis, via the activation of HSCs. Obesity is associated with inflammation, lipodystrophy, and elevated androgen levels, while hyperandrogenemia is correlated with inflammation, apoptosis, and autophagy. Genetic factors, including predisposition and polymorphisms, play a crucial role in the development of MASLD and PCOS, while gut microbiota dysbiosis is associated with insulin resistance, hyperandrogenemia, inflammation, and steatosis. Chronic inflammation associated both with MASLD and PCOS, results in a necro-inflammatory pro-fibrinogenic hepatic environment, predisposing to liver cirrhosis. Created with BioRender.com. Abbreviations include: DAMPs: damage-associated molecular patterns; IKK-β: kappa-B kinase subunit beta; HSC: hepatic stellate cells; IL-1β: interleukin 1β; IL-6: interleukin 6; IRS-PI3K-Akt: Insulin receptor substance-phosphoinositide-3-kinase-Ak strain transforming; JNK1: c-Jun N-terminal kinases 1; MASLD: metabolic dysfunction-associated steatotic…