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-1i-KD). After high-fat diet feeding, Pai-1i-KD and littermate controls did not differ in body weight or energy balance. However, Pai-1i-KD females accumulated smaller inguinal WAT adipocytes. Spectral flow cytometry revealed reduced adipocyte progenitors and macrophages in inguinal WAT. Pai-1i-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.