RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease

Asadipooya, Kamyar; Lankarani, Kamran Bagheri; Raj, Rishi; Kalantarhormozi, Mohammadreza

doi:10.1155/2019/2151302

Cited by 38 publications

(24 citation statements)

References 94 publications

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“…Diaphanous1 (DIAPH1) is a type of formin which is intracellular bind domain of RAGE. The interaction between DIAPH1 with RAGE is essential for RAGE ligand-mediated signalling in multiple cell types [7][8][9].…”

Section: The Biology Of Ragementioning

confidence: 99%

RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage

Feng

Zhu

2020

Adipocyte

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The advanced glycosylation end product receptor (RAGE) acts as a recognition receptor and interacts with different types of ligands that form and accumulate in the tissues and circulation, such as diabetes, inflammation, insulin resistance, and obesity. In these environments, RAGE is expressed on the surface of various cells associated with tissue disturbance. This review mainly summarizes the characteristics of RAGE-related signalling, with a particular emphasis on the role of RAGE in the development of obesity. We also briefly describe the phenotypes and characteristics of macrophages and focus on the role of adipose tissue macrophages (ATMs) and the regulatory mechanisms in obesity, diabetes, and other related metabolic diseases. Besides, we will also elaborate on the prospect of new strategies for treating diabetes and obesity-related metabolic diseases by inhibiting RAGE signalling and regulating ATMs recruitment and polarization.

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Section: The Biology Of Ragementioning

confidence: 99%

RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage

Feng

Zhu

2020

Adipocyte

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“…As mentioned above, AGEs activate multiple intracellular signaling pathways controlling different cellular functions, which in turn lead to pathophysiological effects (36)(37)(38). This is achieved through binding with RAGE triggering different signaling events such as protein kinase C (PKC) activation, nuclear factor kappa-B (NF-κB) accumulation and activation, reactive oxygen species (ROS) generation, and initiation of inflammatory signaling cascades such as the mitogen-activated protein kinase (MAPK) pathway, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNFα), and expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), which together result in the pathogenesis of several diseases (39).…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Products as a Predictor of Diabetes Mellitus in Chronic Hepatitis C-Related Cirrhosis

et al. 2020

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Background and Aims: Advanced glycation end products (AGEs) were found to be involved in the pathogenesis of various disorders. Chronic hepatitis C virus infection is the major cause of liver cirrhosis development and glucose metabolism alteration. We aimed to explore the association of AGEs with the development of diabetes mellitus (DM) in patients with cirrhosis in this study. Methods: Only 144 of the 165 non-diabetic patients with cirrhosis were consecutively included in this prospective cohort pilot study, in addition to 72 healthy control subjects. Clinical data and biochemical parameters including basal insulin secretion and insulin sensitivity indices together with AGEs were evaluated in all participants at baseline and every 1 year thereafter for 2 years. Multivariable Cox regression analysis was used to determine the parameters that could predict the development of DM within this period. Results: DM developed in 14 (10%) patients only. Univariate Cox regression analysis showed that AGEs (P = 0.004), Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.018), HOMA-β (P = 0.015), and age (P = 0.012) were associated with DM. After adjusting multiple confounders, the multivariable Cox regression model showed that AGEs, HOMA-IR, and age were the strongest variables associated with DM (all P < 0.05). Using the receiver operating characteristic curve, AGEs at a cutoff value of more than 82.4 ng/ml had 99.23% specificity, 100% sensitivity, and 0.992 area under the curve (AUC) (all P < 0.001) for DM prediction. Conclusion: Our study suggests that AGEs are related to increased incidence of DM, especially in patients with cirrhosis, which is very promising in lowering the risk of DM in these patients.

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“…AGE induces the production of its RAGE receptor. The AGE-RAGE axis contributes to the accumulation of fat in the liver leading to inflammation, fibrosis, IR, and oxidative stress [107]. Inhibition of AGE formation and mitigation of AGE-mediated effects can be a good therapeutic target for improve both NAFLD and diabetic complications.…”

Section: How T2dm Affects Nash Nash Definitionmentioning

confidence: 99%

Nonalcoholic fatty liver disease and type 2 diabetes: pathophysiological mechanisms shared between the two faces of the same coin

Acierno

Caturano

Pafundi

et al. 2020

Exploration of Medicine

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The pathophysiological mechanisms underlying the close relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are multiple, complex and only partially known. The purpose of this paper was to review the current knowledge of these mechanisms in a unified manner. Subjects with NAFLD and T2DM have established insulin resistance (IR), which exacerbates the two comorbidities. IR worsens NAFLD by increasing the accumulation of free fatty acids (FFAs) in the liver. This occurs due to an increase in the influx of FFAs from peripheral adipose tissue by the activation of hormone-sensitive lipase. In addition, there is de novo increased lipogenesis, a transcription factor, the sterols regulatory element-binding transcription factor 1c (SREBP-1c), which activates the expression of several genes strongly promotes lipogenesis by the liver and facilitate storage of triglycerides. Lipids accumulation in the liver induces a chronic stress in the endoplasmic reticulum of the hepatocytes. Genome-wide association studies have identified genetic variants associated with NAFLD severity, but unrelated to IR. In particular, the alteration of patatin-like phospholipase domain-containing protein 3 contributes to the susceptibility to NAFLD. Furthermore, the lipotoxicity of ceramides and diacylglycerol, well known in T2DM, triggers a chronic inflammatory process favoring the progression from hepatic steatosis to steatohepatitis. Reactive oxygen species produced by mitochondrial dysfunction trigger both liver inflammation and beta-cells damage, promoting the progression of both NAFLD and T2DM. The close association between NAFLD and T2DM is bidirectional, as T2DM may trigger both NAFLD onset and its progression, but NAFLD itself may contribute to the development of IR and T2DM. Future studies on the mechanisms will have to deepen the knowledge of the interaction between the two pathologies and should allow the identification of new therapeutic targets for the treatment of NAFLD, currently substantially absent.

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RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease

Cited by 38 publications

References 94 publications

RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage

RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage

Advanced Glycation End Products as a Predictor of Diabetes Mellitus in Chronic Hepatitis C-Related Cirrhosis

Nonalcoholic fatty liver disease and type 2 diabetes: pathophysiological mechanisms shared between the two faces of the same coin

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