Hepatic NCoR1 deletion exacerbates alcohol-induced liver injury in mice by promoting CCL2-mediated monocyte-derived macrophage infiltration

Yin, Fang‐Fang; Wu, Miaomiao; Wei, Xiaoli; Ren, Ruixue; Liu, Menghua; Chen, Chongqing; Yang, Liu; Xie, Rui-Qian; Jiang, Shanyue; Wang, Xuefu; Wang, Hua

doi:10.1038/s41401-022-00863-0

Cited by 11 publications

(8 citation statements)

References 34 publications

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“…Bmal1 ablation in mice present with increased inflammation, 69 vascular endothelial dysfunction, and atherogenesis 70 and affect lipoproteins. 71 In the liver, hepatocyte-specific Bmal1 knockout mice confer an alteration in metabolic and lipid profile, promoting hyperlipidemia and enhancing atherosclerosis, 72,73 whereas an increase in Bmal1 attenuated liver steatosis, 74 and promoted the upregulation of anti-inflammatory markers Arg1 and IL-10. 75 Gain-of-function studies in mouse endothelial cells and observations in human carotid plaques show that Bmal1 can inhibit atherosclerosis and promote plaque stability by suppressing oxLDL (oxidized-LDL) and ROS accumulation, 76 and in one study, treatment with recombinant Bmal1 decreased total cholesterol in mice.…”

Section: Discussionmentioning

confidence: 99%

PPARγ (Peroxisome Proliferator-Activated Receptor γ) Deacetylation Suppresses Aging-Associated Atherosclerosis and Hypercholesterolemia

Zahr

Liu

Chan

et al. 2023

ATVB

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Background: Atherosclerosis is a medical urgency manifesting at the onset of hypercholesterolemia and is associated with aging. Activation of PPARγ (peroxisome proliferator-activated receptor γ) counteracts metabolic dysfunction influenced by aging, and its deacetylation displays an atheroprotective property. Despite the marked increase of PPARγ acetylation during aging, it is unknown whether PPARγ acetylation is a pathogenic contributor to aging-associated atherosclerosis. Methods: Mice with constitutive deacetylation-mimetic PPARγ mutations on lysine residues K268 and K293 (2KR) in an LDL (low-density lipoprotein)-receptor knockout ( Ldlr −/− ) background ( 2KR:Ldlr −/− ) were aged for 18 months on a standard laboratory diet to examine the cardiometabolic phenotype, which was confirmed in Western-type diet–fed 2KR:Ldlr +/− mice. Whole-liver RNA-sequencing and in vitro studies in bone marrow–derived macrophages were conducted to decipher the mechanism. Results: In contrast to severe atherosclerosis in WT:Ldlr −/− mice, aged 2KR:Ldlr −/− mice developed little to no plaque, which was underlain by a significantly improved plasma lipid profile, with particular reductions in circulating LDL. The protection from hypercholesterolemia was recapitulated in Western-type diet–fed 2KR:Ldlr +/− mice. Liver RNA-sequencing analysis revealed suppression of liver inflammation rather than changes in cholesterol metabolism. This anti-inflammatory effect of 2KR was attributed to polarized M2 activation of macrophages. Additionally, the upregulation of core circadian component Bmal1, perceived to be involved in anti-inflammatory immunity, was observed in the liver and bone marrow–derived macrophages. Conclusions: PPARγ deacetylation in mice prevents the development of aging-associated atherosclerosis and hypercholesterolemia, in association with the anti-inflammatory phenotype of 2KR macrophages.

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Section: Discussionmentioning

confidence: 99%

PPARγ (Peroxisome Proliferator-Activated Receptor γ) Deacetylation Suppresses Aging-Associated Atherosclerosis and Hypercholesterolemia

Zahr

Liu

Chan

et al. 2023

ATVB

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“…An RT-QPCR kit (Takara, Shiga, Japan) was used to synthesize the cDNA, and the results were detected with a real-time PCR system (Bio-Rad Laboratories). 28 We calculated relative mRNA expression levels using the comparative threshold cycle (or 2 Ct) method, and normalized them to GAPDH levels. Primer sequences are shown in Table S1 †…”

Section: Methodsmentioning

confidence: 99%

Manganese Prussian blue nanozymes with antioxidant capacity prevent acetaminophen-induced acute liver injury

Chen

et al. 2023

Biomater. Sci.

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“…Nuclear receptor corepressor 1 (NCoR1) is a corepressor of the epigenetic regulation of gene transcription that has important functions in metabolism and inflammation. Hepatocyte NCoR1 plays distinct roles in controlling liver inflammation and steatosis by promoting fatty acid oxidation and reducing CCL2 gene expression [32].…”

Section: Alcohol-induced Hepatocyte Epigenetic Changesmentioning

confidence: 99%

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression

Osna,

Tikhanovich,

Ortega-Ribera

et al. 2024

Biomolecules

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Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

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Hepatic NCoR1 deletion exacerbates alcohol-induced liver injury in mice by promoting CCL2-mediated monocyte-derived macrophage infiltration

Cited by 11 publications

References 34 publications

PPARγ (Peroxisome Proliferator-Activated Receptor γ) Deacetylation Suppresses Aging-Associated Atherosclerosis and Hypercholesterolemia

PPARγ (Peroxisome Proliferator-Activated Receptor γ) Deacetylation Suppresses Aging-Associated Atherosclerosis and Hypercholesterolemia

Manganese Prussian blue nanozymes with antioxidant capacity prevent acetaminophen-induced acute liver injury

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression

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