Y. Kawabe, J. Mori, Hidechika Morimoto, Mihoko Yamaguchi, S. Miyagaki, T. Ota, Y. Tsuma, S. Fukuhara, Hisakazu Nakajima, G. Oudit, H. Hosoi
American journal of physiology. Endocrinology and metabolism, 2019
Angiotensin II (Ang II)/AngII type1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin converting enzyme 2 (ACE2) counteracts Ang II/AT1R axis via converting Ang II to angiotensin 1-7 (Ang 1-7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang1-7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2) (2.0mg/ kg/day) for 28 days to high-fat diet (HFD) induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, BAT mass increased, accompanied with ameliorated insulin signaling and increased protein levels of UCP-1 and PRDM16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is due to increased H3K27 acetylation via the downregulation of HDAC3 and increased H3K9 acetylation via upregulation of GCN5 and PCAF. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1-7 axis represent a potential therapeutic approach to prevent the development of obesity.
Cited by 16 publications.
Field of study: Medicine