Enhancement of Adipocyte Browning by Angiotensin II Type 1 Receptor Blockade.

Abstract

Browning of white adipose tissue (WAT) has been highlighted as a new possible therapeutic target for obesity, diabetes and lipid metabolic disorders, because WAT browning could increase energy expenditure and reduce adiposity. The new clusters of adipocytes that emerge with WAT browning have been named 'beige' or 'brite' adipocytes. Recent reports have indicated that the renin-angiotensin system (RAS) plays a role in various aspects of adipose tissue physiology and dysfunction. The biological effects of angiotensin II, a major component of RAS, are mediated by two receptor subtypes, angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R). However, the functional roles of angiotensin II receptor subtypes in WAT browning have not been defined. Therefore, we examined whether deletion of angiotensin II receptor subtypes (AT1aR and AT2R) may affect white-to-beige fat conversion in vivo. AT1a receptor knockout (AT1aKO) mice exhibited increased appearance of multilocular lipid droplets and upregulation of thermogenic gene expression in inguinal white adipose tissue (iWAT) compared to wild-type (WT) mice. AT2 receptor-deleted mice did not show miniaturization of lipid droplets or alteration of thermogenic gene expression levels in iWAT. An in vitro experiment using adipose tissue-derived stem cells showed that deletion of the AT1a receptor resulted in suppression of adipocyte differentiation, with reduction in expression of thermogenic genes. These results indicate that deletion of the AT1a receptor might have some effects on the process of browning of WAT and that blockade of the AT1 receptor could be a therapeutic target for the treatment of metabolic disorders.

• Authors: Kana Tsukuda, Masaki Mogi, Jun Iwanami, Harumi Kanno, Hirotomo Nakaoka, Xiao-Li Wang, Hui-Yu Bai, Bao-Shuai Shan, Masayoshi Kukida, Akinori Higaki, Toshifumi Yamauchi, Li-Juan Min, Masatsugu Horiuchi
• Journal: PloS one (PLoS One) Vol. 11 Issue 12 Pg. e0167704 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27992452 (Publication Type: Journal Article)

Chemical References

• Agtr1a protein, mouse
• Mitochondrial Proteins
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2

Topics

• Adipocytes, Brown (cytology, metabolism)
• Adipose Tissue, White (cytology, metabolism)
• Animals
• Cell Differentiation
• Energy Metabolism
• Gene Knockout Techniques
• Male
• Mice
• Mitochondrial Proteins
• Receptor, Angiotensin, Type 1 (genetics, metabolism)
• Receptor, Angiotensin, Type 2 (genetics, metabolism)
• Thermogenesis