Angiotensin receptor subtypes regulate adipose tissue renewal and remodelling

Obesity is often associated with high systemic and local renin-angiotensin system (RAS) activity in adipose tissue. Adipose-derived mesenchymal stem/stromal cells (ADSCs), responsible for adipose tissue growth upon high-fat diet, express multiple angiotensin II receptor isoforms, including angiotensin II type 1 receptor (AT₁ R), angiotensin II type 2 receptor (AT₂ R), Mas and Mas-related G protein-coupled receptor D. Although AT₁ R is expressed on most ADSCs, other angiotensin receptors are co-expressed on a small subpopulation of the cells, a phenomenon that results in a complex response pattern. Following AT₁ R activation, the effects are transient due to rapid receptor internalisation. This short-lived effect can be prevented by heteromerisation with AT₂ R, a particularly important strategy for the regulation of ADSC differentiation and secretory activity. Heteromeric AT₂ R might be especially important for the generation of thermogenic beige adipocytes. This review summarises current data regarding the regulation of adipose tissue renewal and particularly ADSC adipogenic differentiation and secretory activity by RAS, with an emphasis on AT₂ R and its effects. We reveal a new scheme that implicates AT₂ R into the regulation of ADSC hormonal sensitivity.