RNA adenosine deaminase (ADAR1) alleviates high-fat diet-induced nonalcoholic fatty liver disease by inhibiting NLRP3 inflammasome

Xiang, Rong; Liu, Yuxing; Fan, Liang‐Liang; Jiang, Boyue; Wang, Fang

doi:10.1038/s41374-022-00805-8

Cited by 7 publications

(5 citation statements)

References 56 publications

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“…Anyway, in accord with the hypothesis raised here, a lot of chemical agents and herb drugs besides caffeine have been examined in animal studies to see whether some of them could be used as the adequate medicine to attenuate inflammasome activity and slow the progress of alcohol-associated liver disease ( 43 , 44 ), high-fat diet-associated liver disease ( 45 – 48 ), fulminant hepatitis ( 49 ), and acute liver injury ( 50 ). Although we highly suggested that caffeine be tested for similar objectives according to its ability of inhibiting NLRP3 inflammasome activation, caffeine has its own adverse effects when consumed too much, for example, increasing blood pressure, inducing anxiety, reducing skeletal-muscle insulin sensitivity, and decreasing infant birth weights ( 51 ).…”

Section: Discussionmentioning

confidence: 96%

Coffee reduces the risk of hepatocellular carcinoma probably through inhibition of NLRP3 inflammasome activation by caffeine

Fan

2022

Front. Oncol.

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Section: Discussionmentioning

confidence: 96%

Coffee reduces the risk of hepatocellular carcinoma probably through inhibition of NLRP3 inflammasome activation by caffeine

Fan

2022

Front. Oncol.

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“…ADAR2 downregulates miR‐34a, by catalyzing adensosine‐to‐inosine (A‐to‐I) editing of miR‐34a, which inhibits lipogenesis in hepatocytes. In another study, Xiang et al, found ADAR1 to be upregulated in NAFLD patients, and showed that ADAR1 upregulation alleviates NAFLD in a murine model through the impairment of the inflammasome activation in diseased livers (Xiang et al, 2022).…”

Section: Post‐transcriptional Mechanismsmentioning

confidence: 99%

Emerging roles of RNA‐binding proteins in fatty liver disease

Adesanya,

Das,

Kalsotra

2024

WIREs RNA

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A rampant and urgent global health issue of the 21st century is the emergence and progression of fatty liver disease (FLD), including alcoholic fatty liver disease and the more heterogenous metabolism‐associated (or non‐alcoholic) fatty liver disease (MAFLD/NAFLD) phenotypes. These conditions manifest as disease spectra, progressing from benign hepatic steatosis to symptomatic steatohepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma. With numerous intricately regulated molecular pathways implicated in its pathophysiology, recent data have emphasized the critical roles of RNA‐binding proteins (RBPs) in the onset and development of FLD. They regulate gene transcription and post‐transcriptional processes, including pre‐mRNA splicing, capping, and polyadenylation, as well as mature mRNA transport, stability, and translation. RBP dysfunction at every point along the mRNA life cycle has been associated with altered lipid metabolism and cellular stress response, resulting in hepatic inflammation and fibrosis. Here, we discuss the current understanding of the role of RBPs in the post‐transcriptional processes associated with FLD and highlight the possible and emerging therapeutic strategies leveraging RBP function for FLD treatment.This article is categorized under: RNA in Disease and Development > RNA in Disease

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“… 15 A recent study done by Xiang et al has reported that ADAR1 overexpression alleviates HFD‐induced NAFLD by inhibiting the NLRP3 inflammasome. 16 Mice expressing either ADAR2 or inactive ADAR2 isoforms display adult‐onset obesity characterized by hyperglycaemia, hyperleptinaemia and increased adiposity. 17 Exercise‐induced ADAR2 protects against lipogenesis during NAFLD through the editing of miR‐34a.…”

Section: Introductionmentioning

confidence: 99%

“…ADAR1 deficiency attenuates high‐fat diet (HFD)‐induced obesity and insulin resistance (IR) in mice 15 . A recent study done by Xiang et al has reported that ADAR1 overexpression alleviates HFD‐induced NAFLD by inhibiting the NLRP3 inflammasome 16 . Mice expressing either ADAR2 or inactive ADAR2 isoforms display adult‐onset obesity characterized by hyperglycaemia, hyperleptinaemia and increased adiposity 17 .…”

Section: Introductionmentioning

confidence: 99%

ADAR2 deficiency ameliorates non‐alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1

Kung,

Yang,

Lin

et al. 2024

J cachexia sarcopenia muscle

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BackgroundNon‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine‐to‐inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post‐transcriptional modification of genome‐encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity‐associated NAFLD and sarcopenia remains unclear.MethodsADAR2+/+/GluR‐BR/R mice (wild type [WT]) and ADAR2−/−/GluR‐BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high‐fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross‐sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated.ResultsADAR2 KO mice fed with HFD exhibited lower body weight (−7.7%, P < 0.05), lower liver tissue weight (−20%, P < 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (−24%, P < 0.001) and liver injury (P < 0.01). ADAR2 KO mice displayed protection against HFD‐induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P < 0.01), muscle strength (P < 0.05), muscle endurance (P < 0.001) and fibre size (CSA; P < 0.0001) were improved in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. Muscle atrophy‐associated transcripts, such as forkhead box protein O1, muscle atrophy F‐box/atrogin‐1 and muscle RING finger 1/tripartite motif‐containing 63, were decreased in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. ADAR2 deficiency attenuates HFD‐induced local liver and skeletal muscle tissue inflammation. ADAR2 deficiency abolished HFD‐induced systemic (P < 0.01), hepatic (P < 0.0001) and muscular (P < 0.001) SAA1 levels. C2C12 myotubes treated with recombinant SAA1 displayed a decrease in myotube length (−37%, P < 0.001), diameter (−20%, P < 0.01), number (−39%, P < 0.001) and fusion index (−46%, P < 0.01). Myogenic markers (myosin heavy chain and myogenin) were decreased in SAA1‐treated myoblast C2C12 cells.ConclusionsThese results provide novel evidence that ADAR2 deficiency may be important in obesity‐associated sarcopenia and NAFLD. Increased SAA1 might be involved as a regulatory factor in developing sarcopenia in NAFLD.

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RNA adenosine deaminase (ADAR1) alleviates high-fat diet-induced nonalcoholic fatty liver disease by inhibiting NLRP3 inflammasome

Cited by 7 publications

References 56 publications

Coffee reduces the risk of hepatocellular carcinoma probably through inhibition of NLRP3 inflammasome activation by caffeine

Coffee reduces the risk of hepatocellular carcinoma probably through inhibition of NLRP3 inflammasome activation by caffeine

Emerging roles of RNA‐binding proteins in fatty liver disease

ADAR2 deficiency ameliorates non‐alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1

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