Sayej Wael N, Knight Iii Paul R, Guo Weidun Alan, Mullan Barbara, Ohtake Patricia J, Davidson Bruce A, Khan Abdur, Baker Robert D, Baker Susan S
Digestive Diseases, Hepatology and Nutrition Center, Connecticut Children's Medical Center, Hartford, CT 06106, USA; University of Connecticut School of Medicine, Farmington, CT 06032, USA.
Department of Anesthesiology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA; Veterans Administration Western New York Healthcare System, State University of New York at Buffalo, Buffalo, NY 14215, USA; Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Biomed Res Int. 2016;2016:7867852. doi: 10.1155/2016/7867852. Epub 2016 Jan 31.
AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the "multiple hit hypothesis" of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.
晚期糖基化终末产物（AGEs）是一类由还原糖与蛋白质、脂质和/或核酸的游离氨基发生非酶促反应形成的异质性分子。已证明AGEs在包括心血管疾病和糖尿病在内的多种病症中发挥作用。在本研究中，我们假设AGEs在非酒精性脂肪性肝病（NAFLD）的“多重打击假说”中起作用，并促成肝脂肪变性的发病机制。我们测量了在高脂肪或低脂肪含量情况下，含有高AGE或低AGE的各种小鼠饲料对小鼠体重和附睾脂肪垫的影响。我们还通过测量肝脏上清液中的细胞因子水平和髓过氧化物酶活性水平，来测定这些饲料对炎症反应的影响。我们观察到，高AGE-高脂肪（HAGE-HF）组与其他组相比，体重增加和附睾脂肪垫重量存在显著差异。HAGE-HF组的瘦素、肿瘤坏死因子-α、白细胞介素-6和髓过氧化物酶（MPO）水平显著更高。我们得出结论，在高脂肪情况下，含有高AGEs的饮食会导致CD-1小鼠体重增加和肝脂肪变性。这可能代表了一种研究AGEs在肝脂肪变性和脂肪性肝炎发病机制中作用的模型。
