Nishida Nozomi, Sugimoto Satoru, Miyagaki Satoshi, Cho Chiharu, Konishi Madoka, Goda Takeshi, Yamaguchi Mihoko, Kawabe Yasuhiro, Morimoto Hidechika, Kusuyama Joji, Okamura Takuro, Hamaguchi Masahide, Mori Jun, Nakajima Hisakazu, Fukui Michiaki, Iehara Tomoko
Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Biosignals and Inheritance, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Adipocyte. 2025 Dec;14(1):2449027. doi: 10.1080/21623945.2024.2449027. Epub 2025 Jan 13.
Obesity is a global health concern that promotes chronic low-grade inflammation, leading to insulin resistance, a key factor in many metabolic diseases. Angiotensin 1-7 (Ang 1-7), a component of the renin-angiotensin system (RAS), exhibits anti-inflammatory effects in obesity and related disorders, though its mechanisms remain unclear. In this study, we examined the effect of Ang 1-7 on inflammation of white adipose tissue (WAT) in dietary-induced obese mice. Monocyte chemoattractant protein-1 (MCP-1) produced by white adipocytes and tumour necrosis factor-α (TNF-α) produced by macrophages are pro-inflammatory cytokines and interact to form a pathogenic loop to exacerbate obesity-induced inflammation. We found that Ang 1-7 reduced MCP-1 and TNF-α gene expressions and the number of crown-like structures, which are histological hallmarks of the pro-inflammatory process, in visceral epididymal WAT (eWAT) and reduced circulating MCP-1 and TNF-α levels, accompanied by improvement in insulin resistance, in dietary-induced obese mice. Furthermore, Ang 1-7 reduced MCP-1 and TNF-α secretions in 3T3-L1 white adipocytes and RAW 264.7 macrophages, respectively, which are experimental models mimicking obesity condition. Our results suggest that Ang 1-7 directly acts on WAT to mitigate obesity-induced inflammation. Thus, this study provides novel insights into the underlying mechanism of anti-obesity effects of Ang 1-7.
肥胖是一个全球性的健康问题,它会引发慢性低度炎症,导致胰岛素抵抗,而胰岛素抵抗是许多代谢性疾病的关键因素。血管紧张素1-7(Ang 1-7)是肾素-血管紧张素系统(RAS)的一个组成部分,在肥胖及相关疾病中具有抗炎作用,但其机制尚不清楚。在本研究中,我们检测了Ang 1-7对饮食诱导肥胖小鼠白色脂肪组织(WAT)炎症的影响。白色脂肪细胞产生的单核细胞趋化蛋白-1(MCP-1)和巨噬细胞产生的肿瘤坏死因子-α(TNF-α)是促炎细胞因子,它们相互作用形成一个致病循环,加剧肥胖诱导的炎症。我们发现,在饮食诱导肥胖小鼠中,Ang 1-7降低了内脏附睾白色脂肪组织(eWAT)中MCP-1和TNF-α的基因表达以及冠状结构的数量(冠状结构是促炎过程的组织学标志),并降低了循环中MCP-1和TNF-α的水平,同时胰岛素抵抗得到改善。此外,Ang 1-7分别降低了3T3-L1白色脂肪细胞和RAW 264.7巨噬细胞中MCP-1和TNF-α的分泌,这两种细胞是模拟肥胖状态的实验模型。我们的结果表明,Ang 1-7直接作用于白色脂肪组织以减轻肥胖诱导的炎症。因此,本研究为Ang 1-7抗肥胖作用的潜在机制提供了新的见解。