Partial depletion of plasminogen activator inhibitor‐1 decreases subcutaneous fat cell hypertrophy and liver cholesterol in high‐fat‐fed female mice

Higher levels of plasminogen activator inhibitor‐1 (PAI‐1) circulate in the blood of people with obesity and predict hyperlipidemia and metabolic dysfunction‐associated steatotic liver disease in studies predominantly conducted in women. To understand the roles of PAI‐1 in women with obesity, we generated inducible whole‐body PAI‐1‐depleted female mice ( Pai‐1 i‐KD ). After high‐fat diet feeding, Pai‐1 i‐KD and littermate controls did not differ in body weight or energy balance. However, Pai‐1 i‐KD females accumulated smaller inguinal WAT adipocytes. Spectral flow cytometry revealed reduced adipocyte progenitors and macrophages in inguinal WAT. Pai‐1 i‐KD mice also exhibited decreased liver cholesterol. These preclinical findings argue that elevated PAI‐1 alters subcutaneous adipose tissue biology and contributes to pathogenic phenotypes of obesity.