Nakanishi Yuko, Tsuneyama Koichi, Fujimoto Makoto, Salunga Thucydides L, Nomoto Kazuhiro, An Jun-Ling, Takano Yasuo, Iizuka Seiichi, Nagata Mitsunobu, Suzuki Wataru, Shimada Tsutomu, Aburada Masaki, Nakano Masayuki, Selmi Carlo, Gershwin M Eric
Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
J Autoimmun. 2008 Feb-Mar;30(1-2):42-50. doi: 10.1016/j.jaut.2007.11.016.
Chronic inflammation is a common theme in a variety of disease pathways, including autoimmune diseases. The pathways of chronic inflammation are well illustrated by nonalcoholic steatohepatitis (NASH), which is of a serious concern due to its increasing prevalence in the westernized world and its direct correlation with lifestyle factors, particularly diet. Importantly, NASH may ultimately lead to the development of hepatocellular carcinoma. We previously reported that injection of monosodium glutamate (MSG) in ICR mice leads to the development of significant inflammation, central obesity, and type 2 diabetes. To directly address the long-term consequences of MSG on inflammation, we have performed serial analysis of MSG-injected mice and focused in particular on liver pathology. By 6 and 12 months of age, all MSG-treated mice developed NAFLD and NASH-like histology, respectively. In particular, the murine steatohepatitis at 12 months was virtually undistinguishable from human NASH. Further, dysplastic nodular lesions were detected in some cases within the fibrotic liver parenchyma. We submit that MSG treatment of mice induces obesity and diabetes with steatosis and steatohepatitis resembling human NAFLD and NASH with pre-neoplastic lesions. These results take on considerable significance in light of the widespread usage of dietary MSG and we suggest that MSG should have its safety profile re-examined and be potentially withdrawn from the food chain.
慢性炎症是包括自身免疫性疾病在内的多种疾病途径中的一个常见主题。非酒精性脂肪性肝炎（NASH）很好地说明了慢性炎症的途径，由于其在西方世界的患病率不断上升以及与生活方式因素（尤其是饮食）的直接相关性，NASH备受关注。重要的是，NASH最终可能导致肝细胞癌的发生。我们之前报道过，向ICR小鼠注射味精（MSG）会导致明显的炎症、中心性肥胖和2型糖尿病。为了直接研究MSG对炎症的长期影响，我们对注射MSG的小鼠进行了系列分析，并特别关注肝脏病理学。到6个月和12个月大时，所有接受MSG治疗的小鼠分别出现了非酒精性脂肪性肝病（NAFLD）和类似NASH的组织学变化。特别是，12个月大时的小鼠脂肪性肝炎与人类NASH几乎无法区分。此外，在一些纤维化肝实质内还检测到发育异常的结节性病变。我们认为，对小鼠进行MSG治疗会诱发肥胖和糖尿病，并伴有脂肪变性和脂肪性肝炎，类似于人类的NAFLD和NASH，并伴有癌前病变。鉴于膳食MSG的广泛使用，这些结果具有相当重要的意义，我们建议重新审视MSG的安全性，并可能将其从食物链中撤出。
