Control of Adipogenesis by the Autocrine Interplays between Angiotensin 1–7/Mas Receptor and Angiotensin II/AT1 Receptor Signaling Pathways

Angiotensin II (AngII), a peptide hormone released by adipocytes, can be catabolized by adipose angiotensin-converting enzyme 2 (ACE2) to form Ang(1–7). Co-expression of AngII receptors (AT 1 and AT 2 ) and Ang(1–7) receptors (Mas) in adipocytes implies the autocrine regulation of the local angiotensin system upon adipocyte functions, through yet unknown interactive mechanisms. In the present study, we reveal the adipogenic effects of Ang(1–7) through activation of Mas receptor and its subtle interplays with the antiadipogenic AngII-AT1 signaling pathways. Specifically, in human and 3T3-L1 preadipocytes, Ang(1–7)-Mas signaling promotes adipogenesis via activation of PI3K/Akt and inhibition of MAPK kinase/ERK pathways, and Ang(1–7)-Mas antagonizes the antiadipogenic effect of AngII-AT 1 by inhibiting the AngII-AT 1 -triggered MAPK kinase/ERK pathway. The autocrine regulation of the AngII/AT 1 -ACE2-Ang(1–7)/Mas axis upon adipogenesis has also been revealed. This study suggests the importance of the local regulation of the delicately balanced angiotensin system upon adipogenesis and its potential as a novel therapeutic target for obesity and related metabolic disorders. Background: The autocrine regulation of Ang(1–7) upon adipogenesis is unknown. Results: The autocrine counteractive interplays between Ang(1–7)-Mas and AngII-AT 1 signaling upon adipogenesis are revealed. Conclusion: The Ang(1–7)-Mas activation stimulates adipogenesis and antagonizes the antiadipogenic effect of AngII-AT 1 activation. Significance: The angiotensin system in adipose tissue may serve as a potential therapeutic target for obesity and related metabolic disorders.