Endoplasmic reticulum stress in innate immune cells - a significant contribution to non-alcoholic fatty liver disease

Zhou, Liangliang; Shen, Haiyuan; Li, Xiaofeng; Wang, Hua

doi:10.3389/fimmu.2022.951406

Cited by 12 publications

(11 citation statements)

References 141 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KC cells are the rst line of defense in the liver. When the HFHCC diet induces disorders of glucose and lipid metabolism, lipotoxicity caused by excessive accumulation of lipids in hepatocytes activates macrophages, leading to TNF-α, IL-6, and IL-1β, which further promotes liver steatosis, in ammation, and liver brosis [15]. In this study, In this study, immunohistochemical results showed that the HFHFF diet induced the activation of KCs.…”

Section: Discussionsupporting

confidence: 50%

A high-trans fat, high-carbohydrate, high-cholesterol diet-induced nonalcoholic steatohepatitis mouse model and its hepatic immune response

Zhang

Jin

Xin

et al. 2022

Preprint

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive disease that can progress to non-alcoholic steatohepatitis (NASH). Animal models are important tools for basic NASH research. Immune activation plays a key role in liver inflammation in patients with NASH. We established a high-trans fat, high-carbohydrate, and high-cholesterol diet-induced (HFHCC) mouse model. C57BL/6 mice were fed a normal or HFHCC diet for 24 weeks, and the immune response characteristics of this model were evaluated. The results showed that mice treated with HFHCC diet exhibited remarkably increased hepatic triglycerides (TG)content, and the increase in plasma transaminases resulted in hepatocyte injury. Biochemical results showed that HFHCC induced glucose and lipid metabolism disorders; marked hepatocyte steatosis, ballooning, inflammation, and fibrosis. The proportion of innate immunity-related cells, including Kupffer cells (KCs), neutrophils, dendritic cells (DCs), natural killer T cells (NKT), and adaptive immunity-related CD3 + T cells increased; interleukin-1α (IL-1α), IL-1β, IL-2, IL-6, IL-9, and chemokines, including CCL2, CCL3, and macrophage colony stimulating factor (G-CSF) increased. The constructed model closely approximated the characteristics of human NASH and evaluation of its immune response signature, showed that the innate immune response was more pronounced than adaptive immunity. Its use as an experimental tool for understanding innate immune responses in NASH is recommended.

show abstract

Section: Discussionsupporting

confidence: 50%

A high-trans fat, high-carbohydrate, high-cholesterol diet-induced nonalcoholic steatohepatitis mouse model and its hepatic immune response

Zhang

Jin

Xin

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The latest study indicated that ER stress in innate immune cells contributes to NASH. For example, ATF6, by mediating a proinflammatory synergy between ER stress and TLR activation, is involved in the development of liver injury [ 35 ]. XBP1-mediated ER stress promoted steatohepatitis via NLRP3 inflammatory vesicle-mediated M1-type polarization [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte-Derived Prostaglandin E2-Modulated Macrophage M1-Type Polarization via mTOR-NPC1 Axis-Regulated Cholesterol Transport from Lysosomes to the Endoplasmic Reticulum in Hepatitis B Virus x Protein-Related Nonalcoholic Steatohepatitis

Lan

Qian

Huang

et al. 2022

IJMS

View full text Add to dashboard Cite

Lipid metabolic dysregulation and liver inflammation have been reported to be associated with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain unclear. Hepatitis B virus x protein (HBx) is a risk factor for NASH. Based on metabolomic and transcriptomic screens and public database analysis, we found that HBx-expressing hepatocyte-derived prostaglandin E2 (PGE2) induced macrophage polarization imbalance via prostaglandin E2 receptor 4 (EP4) through in vitro, ex vivo, and in vivo models. Here, we revealed that the M1-type polarization of macrophages induced by endoplasmic reticulum oxidoreductase-1-like protein α (ERO1α)-dependent endoplasmic reticulum stress was associated with the HBx-related hepatic NASH phenotype. Mechanistically, HBx promoted Niemann–Pick type C1 (NPC1)/oxysterol-binding protein-related protein 5 (ORP5)-mediated cholesterol transport from the lysosome to the endoplasmic reticulum via mammalian target of rapamycin (mTOR) activation. This study provides a novel basis for screening potential biomarkers in the macrophage mTOR–cholesterol homeostasis–polarization regulatory signaling pathway and evaluating targeted interventions for HBx-associated NASH.

show abstract

“…This condition leads to the activation of transcription factors sensitive to oxidative stress, such as NF- κB. These, in turn, trigger Kupffer cells to produce pro-inflammatory mediators and further promote NAFLD progression [ 109 ].…”

Section: Pathogenesismentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma

2023

View full text Add to dashboard Cite

In clinical practice, we often deal with patients who suffer from non-alcoholic fatty liver disease (NAFLD) concurrent with type 2 diabetes mellitus (T2DM). The etiopathogenesis of NAFLD is mainly connected with insulin resistance (IR) and obesity. Similarly, the latter patients are in the process of developing T2DM. However, the mechanisms of NAFLD and T2DM coexistence have not been fully elucidated. Considering that both diseases and their complications are of epidemic proportions and significantly affect the length and quality of life, we aimed to answer which of these diseases appears first and thereby highlight the need for their diagnosis and treatment. To address this question, we present and discuss the epidemiological data, diagnoses, complications and pathomechanisms of these two coexisting metabolic diseases. This question is difficult to answer due to the lack of a uniform procedure for NAFLD diagnosis and the asymptomatic nature of both diseases, especially at their beginning stages. To conclude, most researchers suggest that NAFLD appears as the first disease and starts the sequence of circumstances leading ultimately to the development of T2DM. However, there are also data suggesting that T2DM develops before NAFLD. Despite the fact that we cannot definitively answer this question, it is very important to bring the attention of clinicians and researchers to the coexistence of NAFLD and T2DM in order to prevent their consequences.

show abstract

Endoplasmic reticulum stress in innate immune cells - a significant contribution to non-alcoholic fatty liver disease

Cited by 12 publications

References 141 publications

A high-trans fat, high-carbohydrate, high-cholesterol diet-induced nonalcoholic steatohepatitis mouse model and its hepatic immune response

A high-trans fat, high-carbohydrate, high-cholesterol diet-induced nonalcoholic steatohepatitis mouse model and its hepatic immune response

Hepatocyte-Derived Prostaglandin E2-Modulated Macrophage M1-Type Polarization via mTOR-NPC1 Axis-Regulated Cholesterol Transport from Lysosomes to the Endoplasmic Reticulum in Hepatitis B Virus x Protein-Related Nonalcoholic Steatohepatitis

Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma

Contact Info

Product

Resources

About