Critical Role of Hepatic Fatty-Acyl Phospholipid Remodeling in Obese and Nonobese Fatty Liver Mouse Models

2019 ◽  
pp. 239-256
Author(s):  
Walee Chamulitrat ◽  
Gerhard Liebisch ◽  
Anita Pathil ◽  
Wolfgang Stremmel
Keyword(s):  
Fatty Liver ◽  
Mouse Models ◽  
Critical Role ◽  
Fatty Acyl

scholarly journals Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

2020 ◽  
Author(s):  
Olivier Govaere ◽  
Nuria Martinez-Lopez ◽  
Sine Kragh Petersen ◽  
Rosellina M. Mancina ◽  
Oveis Jamialahmadi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Alcoholic Fatty Liver ◽  
Macrophage Scavenger Receptor ◽  
Foamy Macrophages ◽  
Alcoholic Fatty Liver Disease

AbstractObesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), however the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1) is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a large cohort of NAFLD patients. Mice lacking Msr1 are protected against high fat diet-induced metabolic disorder, showing less hepatic inflammation and fibrosis, reduced circulating fatty acids, increased lipid storage in the adipocytes and improved glucose tolerance. Moreover, MSR1 triggers diet-induced JNK-mediated inflammatory activation of macrophages independent of lipopolysaccharide. Taken together, our data suggest a critical role for MSR1 in lipid homeostasis and a potential therapeutic target for the treatment of NAFLD.One Sentence SummaryThe immunometabolic role of MSR1 in human NAFLD.

The critical role of redox regulation of PTEN and peroxiredoxin III in alcoholic fatty liver

2021 ◽  
Vol 162 ◽  
pp. 141-148
Author(s):  
Ying Zhang ◽  
Jiyoung Park ◽  
Seong-Jeong Han ◽  
Iha Park ◽  
Thang Nguyen Huu ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Redox Regulation ◽  
Critical Role ◽  
Alcoholic Fatty Liver

scholarly journals Role of Neutrophils in the Pathogenesis of Nonalcoholic Steatohepatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Seonghwan Hwang ◽  
Hwayoung Yun ◽  
Sungwon Moon ◽  
Ye Eun Cho ◽  
Bin Gao
Keyword(s):  
Fatty Liver ◽  
Nonalcoholic Steatohepatitis ◽  
Critical Role ◽  
Neutrophil Infiltration ◽  
Neutrophil Extracellular Trap ◽  
First Line ◽  
Nonalcoholic Fatty Liver ◽  
Inflammation Resolution ◽  
Species Production

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of liver disorders, from fatty liver to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Compared with fatty liver, NASH is characterized by increased liver injury and inflammation, in which liver-infiltrating immune cells, with neutrophil infiltration as a hallmark of NASH, play a critical role in promoting the progression of fatty liver to NASH. Neutrophils are the first responders to injury and infection in various tissues, establishing the first line of defense through multiple mechanisms such as phagocytosis, cytokine secretion, reactive oxygen species production, and neutrophil extracellular trap formation; however, their roles in the pathogenesis of NASH remain obscure. The current review summarizes the roles of neutrophils that facilitate the progression of fatty liver to NASH and their involvement in inflammation resolution during NASH pathogenesis. The notion that neutrophils are potential therapeutic targets for the treatment of NASH is also discussed.

scholarly journals Dysregulation of the Tweak/Fn14 pathway in skeletal muscle of spinal muscular atrophy mice

2021 ◽  
Author(s):  
Katharina E Meijboom ◽  
Emily McFall ◽  
Daniel Anthony ◽  
Benjamin Edwards ◽  
Sabrina Kubinski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spinal Muscular Atrophy ◽  
Mouse Models ◽  
Muscle Atrophy ◽  
Muscular Atrophy ◽  
Critical Role ◽  
Pharmacological Intervention ◽  
Muscle Pathology ◽  
Developing Muscle

Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle. We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn-/-;SMN2 and the less severe Smn2B/- SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. Here, we report significantly dysregulated expression of the TWEAK/Fn14 pathway during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak-/- and Fn14-/- mice revealed dysregulated myopathy, myogenesis and glucose metabolism pathways as a common skeletal muscle feature, and providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, a pharmacological intervention (Fc-TWEAK) to upregulate the activity of the TWEAK/Fn14 pathway improved disease phenotypes in the two SMA mouse models. Our study provides novel mechanistic insights into the molecular players that contribute to muscle pathology in SMA and into the role of the TWEAK/Fn14 pathway in developing muscle.

scholarly journals Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1660
Author(s):  
Han Zhang ◽  
Enxiang Zhang ◽  
Hongbo Hu
Keyword(s):  
Lipid Peroxidation ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Critical Role ◽  
Iron Storage ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease ◽  
Selection Of

Non-alcoholic fatty liver disease (NAFLD) has become the chronic liver disease with the highest incidence throughout the world, but its pathogenesis has not been fully elucidated. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Abnormal iron metabolism, lipid peroxidation, and accumulation of polyunsaturated fatty acid phospholipids (PUFA-PLs) can all trigger ferroptosis. Emerging evidence indicates that ferroptosis plays a critical role in the pathological progression of NAFLD. Because the liver is the main organ for iron storage and lipid metabolism, ferroptosis is an ideal target for liver diseases. Inhibiting ferroptosis may become a new therapeutic strategy for the treatment of NAFLD. In this article, we describe the role of ferroptosis in the progression of NAFLD and its related mechanisms. This review will highlight further directions for the treatment of NAFLD and the selection of corresponding drugs that target ferroptosis.

scholarly journals Role of MicroRNAs in Pathophysiology of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis

2018 ◽  
Vol 10 (4) ◽  
pp. 213-219 ◽  
Author(s):  
Farzaneh Iravani ◽  
Neda Hosseini ◽  
Majid Mojarrad
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Critical Role ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. It includes wide range of diseases from different subtypes of simple steatosis to non-alcoholic steatohepatitis (NASH), which may be complicated by liver fibrosis, cirrhosis, or hepatocellular carcinoma. Of the epigenetic factors that play a key role in the progression of it, is microRNAs (miRNAs). MiRNAs are short non-coding RNAs of 22-23 nucleotides in length, which regulate a large number of genes that have a critical role in regulation of lipid and cholesterol biosynthesis in hepatocytes. MiRNAs can be used as a very powerful biomarker to diagnosis and follow-up any disorder, such as NAFLD and NASH with a high specificity and sensitivity. The aim of this study was to review the role of different miRNAs in the pathophysiology of NASH and NAFLD.

scholarly journals The Role of the IL-23/IL-17 Pathway in the Pathogenesis of Spondyloarthritis

2020 ◽  
Vol 21 (17) ◽  
pp. 6401 ◽  
Author(s):  
Hiroyuki Tsukazaki ◽  
Takashi Kaito
Keyword(s):  
Inflammatory Bowel Disease ◽  
Ankylosing Spondylitis ◽  
Mouse Models ◽  
Clinical Studies ◽  
Current Knowledge ◽  
Critical Role ◽  
Joint Inflammation ◽  
The Past ◽  
Inflammatory Bowel

Spondyloarthritis (SpA) is a subset of seronegative rheumatic-related autoimmune diseases that consist of ankylosing spondylitis (AS), psoriatic spondylitis (PsA), reactive spondylitis (re-SpA), inflammatory bowel disease (IBD)-associated spondylitis, and unclassifiable spondylitis. These subsets share clinical phenotypes such as joint inflammation and extra-articular manifestations (uveitis, IBD, and psoriasis [Ps]). Inflammation at the enthesis, where ligaments and tendons attach to bones, characterizes and distinguishes SpA from other types of arthritis. Over the past several years, genetic, experimental, and clinical studies have accumulated evidence showing that the IL-23/IL-17 axis plays a critical role in the pathogenesis of SpA. These discoveries include genetic association and the identification of IL-23- and IL-17-producing cells in the tissue of mouse models and human patients. In this review, we summarize the current knowledge of the pathomechanism by focusing on the IL-23/IL-17 pathway and examine the recent clinical studies of biological agents targeting IL-23 and IL-17 in the treatment of SpA.

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