The NE/AAT/CBG axis regulates adipose tissue glucocorticoid exposure.

ABSTRACT: Corticosteroid binding globulin (CBG; SERPINA6) binds >85% of circulating glucocorticoids but its influence on their metabolic actions is unproven. Targeted proteolytic cleavage of CBG by neutrophil elastase (NE; ELANE) significantly reduces CBG binding affinity, potentially increasing 'free' glucocorticoid levels at sites of inflammation. NE is inhibited by alpha-1-antitrypsin (AAT; SERPINA1). Using complementary approaches in mice and humans to manipulate NE or AAT, we show high-fat diet (HFD) increases the NE:AAT ratio specifically in murine visceral adipose tissue, an effect only observed in males. Notably, HFD-fed male mice lacking NE have reduced glucocorticoid levels and action specifically in visceral adipose tissue, with improved glucose tolerance and insulin sensitivity, independ

SUBMITTER: Boyle LD 

PROVIDER: S-EPMC11718191 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature