Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease

Klepp, T. D.; Sloan, Matthew E.; Soundararajan, Soundarya; Ramsden, Christopher E.; Çınar, Reşat; Schwandt, Melanie L.; Diazgranados, Nancy; Vatsalya, V; Ramchandani, Vijay A.

doi:10.1016/j.alcohol.2022.04.001

Cited by 3 publications

(3 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deficiency of LBP resulted in pronounced H3K27 hyper-acetylation, which facilitated the binding of C/EBPβ to the promoter region, leading to the activation of SCD . This gene, a vital marker of lipid metabolism, is frequently associated with the acceleration of fatty liver disorder progression due to its role in lipid deposition ( Klepp et al, 2022 ; Zhang et al, 2020 ). Emerging evidence has suggested that SCD plays a potential role in triggering lipid accumulation through FAO suppression ( Dobrzyn et al, 2004 ; Kim et al, 2011 ; Ntambi et al, 2002 ), as confirmed by the decreased expression of various FAO-related genes in our study.…”

Section: Discussionmentioning

confidence: 99%

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

Zhu,

Meng,

et al. 2024

Zoological Research

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is associated with mutations in lipopolysaccharide-binding protein ( LBP ), but the underlying epigenetic mechanisms remain understudied. Herein, LBP -/- rats with NAFLD were established and used to conduct integrative targeting-active enhancer histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency. Notably, LBP -/- reduced the inflammatory response but markedly aggravated high-fat diet (HFD)-induced NAFLD in rats, with pronounced alterations in the histone acetylome and regulatory transcriptome. In total, 1 128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type (WT) and LBP -/- NAFLD rats. Based on integrative analysis, CCAAT/enhancer-binding protein β (C/EBPβ) was identified as a pivotal transcription factor (TF) and contributor to dysregulated histone acetylome H3K27ac, and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD. This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβ and functional gene SCD as potential regulators and therapeutic targets.

show abstract

Section: Discussionmentioning

confidence: 99%

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

Zhu,

Meng,

et al. 2024

Zoological Research

View full text Add to dashboard Cite

show abstract

“…As the leading cause of liver-related diseases worldwide, ALD is caused by heavy drinking. The initial manifestation is the accumulation of lipids, including triglycerides, appearing as a large number of lipid droplets that can be observed by oil red O staining ( 9 ). The next step is to develop alcoholic hepatitis, and the most obvious indication is the change of enzymology demonstrated by a significant increase of ALT and AST which are two key biological indicators for evaluating liver function ( 10 , 11 ).…”

Section: Discussionmentioning

confidence: 99%

Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease

Yang,

Wang,

Cui

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

show abstract

“…The alcohol dependence module of the Structured Clinical Interview I, and alcohol withdrawal were administered for reaching the AUD diagnosis. All study patients received medical management and addiction therapy throughout their stay; more details are available in our previous publications [ 34 , 35 ]. Further detailed information on admission, exclusion, and inclusion could be reviewed in a primary publication on investigational drug efficacy [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients

Winrich

Gala

Rajhans

et al. 2022

IJMS

View full text Add to dashboard Cite

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients were sub-divided within each group into patients with normal magnesium (0.85 and more mmol/L) and deficient magnesium (less than 0.85 mmol/L) levels. All participants were assessed at baseline (BL) and received standard medical management for 2 weeks with reassessment at the treatment end (2w). (3) Female participants of this study showed a significantly lower baseline level of magnesium than their male counterparts. Gr.2 patients showed a greater propensity in the necrotic type of liver cell death, who reported higher chronic and recent heavy drinking. Magnesium level improved to the normal range in Gr.2 post-treatment, especially in the hypomagnesemia sub-group (0.77 ± 0.06 mmol/L (BL) vs. 0.85 ± 0.05 mmol/L (2w), p = 0.02). In Gr.2, both apoptotic (K18M30) and necrotic (K18M65) responses were significantly and independently associated with inflammasome activity comprising of LBP (Lipopolysaccharide binding-protein) and TNFα (Tumor necrosis factor -α), along with serum magnesium. (4) In AUD patients with liver injury, 2-week medical management seems to improve magnesium to a normal level. This group exhibited inflammatory activity (LBP and TNFα) contributing to clinically significant hypomagnesemia. In this group, the level of magnesium, along with the unique inflammatory activity, seems to significantly predict apoptotic and necrotic types of hepatocyte death.

show abstract

Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease

Cited by 3 publications

References 42 publications

Loss of <i>LBP</i> triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-<i>SCD</i> activation in non-alcoholic fatty liver disease

Loss of <i>LBP</i> triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-<i>SCD</i> activation in non-alcoholic fatty liver disease

Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease

Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients

Contact Info

Product

Resources

About