Angiotensin II type 2 receptor signaling affects dopamine levels in the brain and prevents binge eating disorder

• Main Authors: Hirotomo Nakaoka, Masaki Mogi, Harumi Kan-no, Kana Tsukuda, Kousei Ohshima, Xiao-Li Wang, Toshiyuki Chisaka, Hui-Yu Bai, Bao-Shuai Shan, Masayoshi Kukida, Jun Iwanami, Masatsugu Horiuchi
• Format: Article
• Language: English
• Published: Hindawi - SAGE Publishing 2015-12-01
• Series: Journal of the Renin-Angiotensin-Aldosterone System
• Online Access: https://doi.org/10.1177/1470320315573680
• ISSN: 1470-3203; 1752-8976

Introduction: Binge eating disorder (BED) is associated with dopaminergic activation as food reward, resulting in metabolism-related disorders. Stimulation of angiotensin type 2 (AT 2 ) receptor is reported to inhibit dopamine synthesis. We investigated the possible roles of AT 2 receptor-mediated dopamine regulation in the pathogenesis of BED. Materials and methods: Male C57BL/6 mice, type 2 diabetic (KKAy) mice and AT 2 receptor-null (AT 2 KO) mice at eight weeks old were treated with AT 2 receptor agonist, compound 21 (C21) or saline for two weeks. Mice were subjected to fasting for two days followed by re-feeding for seven days. Results: Treatment with C21 attenuated the rebound proportion of body weight, food intake and water intake in KKAy mice, but not in C57BL/6 and AT 2 KO mice. Dopamine concentration in the striatum was further increased by fasting in KKAy and AT 2 KO mice. Administration of C21 significantly attenuated this fasting-induced increase in dopamine level only in KKAy mice. Dopamine receptor D1, D2 expression in the substantia nigra were markedly lower in KKAy mice compared with C57BL/6 mice, while administration of C21 increased their expression in KKAy mice. Conclusions: Our study suggests that AT 2 receptor stimulation may be a new therapeutic approach to improve eating disorder associated with dopamine resistance.