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

Authors

Claudia E Ramirez Bustamante, Robert Sharp, Pradip K Saha, Elizabeth S Anaya, Elizabeth L Lieu, Evelyn L de Groot, Pooja Patel, Mi Jeong Heo, Aaron R Cox, Kang Ho Kim, Sean M Hartig

Published in

FEBS letters. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

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.

PMID:
42629995
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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