Abstract
Non-alcoholic fatty liver disease (NAFLD) has become a common chronic disease in the world. NAFLD is not only a simple intrahepatic lesion, but also affects the occurrence of a variety of extrahepatic complications. In particular, cardiovascular complications are particularly serious, which is the main cause of death in patients with NAFLD. To study the relationship between NAFLD and AS may be a new way to improve the quality of life in patients with NAFLD. As we all known, inflammatory response plays an important role in the occurrence and development of NAFLD and AS. In this study, we found that the accumulation of Nε-carboxymethyllysine (CML) in the liver leads to hepatic steatosis. CML can induce the expression of interleukin (IL-1β), interleukin (IL-6), tumor necrosis factor (TNF-α), C-reactionprotein (CRP) by binding with advanced glycosylation end-product receptor (RAGE) and accelerate the development of AS. After silencing RAGE expression, the expression of pro-inflammatory cytokines was inhibited and liver and aorta pathological changes were relieved. In conclusion, CML/RAGE signal promotes the progression of non-alcoholic fatty liver disease and atherosclerosis. We hope to provide new ideas for the study of liver vascular dialogue in multi organ communication.
Highlights
With economic development, improvement in living standards, the prevalence of a high-fat, high-calorie diet, the acceleration of life and the prevalence of a lifestyle of less movement and more sitting, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing [1, 2]
We detected the expression of the CML receptor receptor for AGEs (RAGE) by immunohistochemistry and found that RAGE was significantly expressed on the steatotic liver cell membrane (Figures 1A,C)
We hypothesize that liver steatosis may be related to CML accumulation and CML may play a role in inducing liver inflammation by binding with RAGE
Summary
Improvement in living standards, the prevalence of a high-fat, high-calorie diet, the acceleration of life and the prevalence of a lifestyle of less movement and more sitting, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing [1, 2]. NAFLD refers to excessive fat deposition in the liver in the absence of ethanol and other clear causes. The global prevalence of NAFLD has reached 25.2% [6]. NAFLD has no obvious symptoms in the early stage, and liver fat infiltration of 30% or more can be diagnosed by liver ultrasound [7,8,9]. As NAFLD is difficult to diagnose and its prevalence is likely to be underestimated
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