The short ACE2 isoform is upregulated in adipose tissue from women with obesity

A novel short ACE2 isoform, lacking the SARS-CoV-2 binding domain and upregulated by interferons, was recently identified in human respiratory epithelia, spermatozoa, liver, and gastrointestinal and urogenital tracts. This study is the first to describe its presence in human adipose tissue (AT).

AT samples were collected from middle-aged women without obesity in subcutaneous regions-abdominal superficial, abdominal deep, and thigh-as well as from the visceral epiploon. Subcutaneous abdominal AT was also obtained from middle-aged women with previous obesity and from older women with and without obesity. Short ACE2 expression was determined by immunohistochemistry and Western blotting in AT, mature adipocytes, and stromal vascular fraction (SVF).

Short ACE2 showed comparable expression in both subcutaneous and visceral AT, with enrichment in adipocytes. In contrast, full-length ACE2 displayed a different pattern, as its levels did not significantly differ between the SVF and adipocytes. Moreover, short ACE2 levels were higher in AT from women with obesity compared with those without obesity. Interestingly, short ACE2 expression was also elevated in AT from women with previous obesity.

Given that short ACE2 expression is induced by interferons, its upregulation in AT under obesity may reflect the interferon-enriched inflammatory environment characteristic of this condition. These findings identify AT, particularly adipocytes, as a relevant site for short ACE2 expression and regulation, expanding current knowledge on short ACE2 isoform biology.