The CYP4/20-HETE/GRP75 axis in the progression metabolic dysfunction-associated steatosis liver disease (MASLD) to chronic liver disease DOI Creative Commons

James P. Hardwick,

Byoung‐Joon Song,

Paul Rote

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 29, 2025

Introduction Metabolic-dysfunction-associated steatosis liver disease (MASLD) is a progressive from simple steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Chronic diseases (CLDs) can lead to portal hypertension, which major cause of complications cirrhosis. CLDs structural alterations across the through increased contents extracellular matrix (ECM), driving dysfunction sinusoidal endothelial cells (LSECs) alongside hepatic stellate (HSCs) activated resident or infiltrating immune cells. Bioactive arachidonic metabolites have diverse roles in progression MASLD. Both secreted levels 20-hydroxyeicosatetraenoic acid (20-HETE) epoxyeicosatrienoic (EET) are elevated patients with Methods CLD samples were evaluated for changes free fatty acids (FFA), cholesterol, bilirubin, bile acid, reactive oxygen species (ROD), lipid peroxidation, myeloperoxidase activity hydroxyproline evaluate degrees damage fibrosis. To address role CYP4/20-HETE/GPR75 axis, we measured amount synthesis 20-HETE CLD, specifically during Additionally, gene expression protein GPR75, high-affinity receptor patient samples. Results We observed an increase Increased correlated CYP4A11 genes but not CYP4F2. These results confirmed by P4504A11 decreased P4504F2 development The 20-HETE, Interestingly, GPR75 mRNA steatohepatitis dramatically dropped cirrhosis then HCC. Also, mirrored their levels. Discussion indicate that subsequent coordinately regulated MASLD may multiple roles, including activation peroxisome proliferator-activated α (PPARα) either cell proliferation vasoconstriction hypertension abrupt reduction also be due serving as feedback mechanism via , leading reduced expression. This work illustrates key correlations associated axis humans.

Language: Английский

Alcohol-associated liver disease DOI Creative Commons
Bryan Mackowiak, Yaojie Fu, Luca Maccioni

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(3)

Published: Feb. 1, 2024

Alcohol-associated liver disease (ALD) is a major cause of chronic worldwide, and comprises spectrum several different disorders, including simple steatosis, steatohepatitis, cirrhosis, superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field ALD over last 20 years, pathogenesis remains obscure, there are currently no FDA-approved drugs for treatment ALD. In this Review, we discuss new insights into therapeutic targets ALD, utilizing study multiomics other cutting-edge approaches. The potential translation these studies clinical practice therapy deliberated. We also preclinical models interplay metabolic dysfunction, alcohol-associated cancer, heterogeneity some translational research prospects

Language: Английский

Citations

115
Polyphyllin I induced ferroptosis to suppress the progression of hepatocellular carcinoma through activation of the mitochondrial dysfunction via Nrf2/HO-1/GPX4 axis DOI
Renyi Yang, Wenhui Gao, Zhibing Wang

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 122, P. 155135 - 155135

Published: Oct. 12, 2023

Language: Английский

Citations

76
Metabolic reprogramming in liver fibrosis DOI Creative Commons
Paul Horn, Frank Tacke

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(7), P. 1439 - 1455

Published: May 31, 2024

Chronic liver diseases, primarily metabolic dysfunction-associated steatotic disease (MASLD), harmful use of alcohol, or viral hepatitis, may result in fibrosis, cirrhosis, and cancer. Hepatic fibrogenesis is a complex process with interactions between different resident non-resident heterogeneous cell populations, ultimately leading to deposition extracellular matrix organ failure. Shifts phenotypes functions involve pronounced transcriptional protein synthesis changes that require adaptations cellular substrate metabolism, including glucose lipid resembling associated the Warburg effect cancer cells. Cell activation are regulated by stress responses, unfolded response, endoplasmic reticulum stress, autophagy, ferroptosis, nuclear receptor signaling. These crucial for inflammatory fibrogenic macrophages, lymphoid cells, hepatic stellate Modulation these pathways, therefore, offers opportunities novel therapeutic approaches halt even reverse fibrosis progression.

Language: Английский

Citations

67
Comparison of NAFLD, MAFLD and MASLD characteristics and mortality outcomes in United States adults DOI
Rui Song, Li Zhao, Yingzhi Zhang

et al.

Liver International, Journal Year: 2024, Volume and Issue: 44(4), P. 1051 - 1060

Published: Jan. 31, 2024

Abstract Background & Aims Following the classification of metabolic dysfunction‐associated fatty liver disease (MAFLD), non‐alcoholic (NAFLD) has recently been redefined again as steatotic (MASLD). However, distinctions in characteristics and mortality outcomes between NAFLD, MAFLD MASLD remain unclear. Methods We analysed data from 7519 participants third National Health Nutrition Examination Surveys United States (US) their linked until 2019. Survey weight‐adjusted multivariable Cox proportional model was used to study over three terms. Results The prevalence 18.5%, 19.3% 20.8%, respectively. Most individuals with NAFLD (94.5%) or (100%) can be classified MASLD, while a relatively low percentage those were also diagnosed either (84.1%) (92.7%). During median follow‐up 26.9 years, both associated increased risk all‐cause (adjusted hazard ratio [aHR] 1.18, 95% CI 1.04–1.33 1.19, 1.06–1.34, respectively), this association mainly observed NAFLD−/MASLD+ subgroups. not mortality. all terms an advanced fibrosis (aHR: 1.71–1.81). Subgroup analyses showed that higher for among older adults (≥65 year), non‐Hispanic whites without diabetes. Conclusions Both MALFD risk, but identified greater number compared MAFLD.

Language: Английский

Citations

49
Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction DOI Creative Commons
Karli R. LeFort, Wiramon Rungratanawanich, Byoung‐Joon Song

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Abstract This review provides an update on recent findings from basic, translational, and clinical studies the molecular mechanisms of mitochondrial dysfunction apoptosis hepatocytes in multiple liver diseases, including but not limited to alcohol-associated disease (ALD), metabolic dysfunction-associated steatotic (MASLD), drug-induced injury (DILI). While ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via microsomal ethanol system, it also metabolizing many xenobiotics, pollutants, chemicals, drugs, specific diets abundant n-6 fatty acids, into toxic metabolites organs, liver, causing pathological insults through organelles such as mitochondria endoplasmic reticula. Oxidative imbalances (oxidative stress) promote covalent modifications lipids, proteins, nucleic acids enzymatic non-enzymatic mechanisms. Excessive changes stimulate various post-translational (PTMs) transcription factors, histones. Increased PTMs proteins inactivate enzymes involved reduction oxidative species, acid metabolism, mitophagy pathways, leading dysfunction, energy depletion, apoptosis. Unique other organelles, control signaling cascades bioenergetics (fat metabolism), inflammation, apoptosis/necrosis hepatocytes. When homeostasis shifted, these pathways become altered or shut down, likely contributing death with activation inflammation hepatic stellate cells, fibrosis cirrhosis. will encapsulate how contributes hepatocyte several types diseases order provide recommendations targeted therapeutics.

Language: Английский

Citations

36
WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography DOI Creative Commons
Giovanna Ferraioli, R. Graham Barr, Annalisa Berzigotti

et al.

Ultrasound in Medicine & Biology, Journal Year: 2024, Volume and Issue: 50(8), P. 1071 - 1087

Published: May 17, 2024

Language: Английский

Citations

33
Direct-acting antiviral therapies for hepatitis C infection: global registration, reimbursement, and restrictions DOI
Alison D. Marshall,

Alex Willing,

Abe Kairouz

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2024, Volume and Issue: 9(4), P. 366 - 382

Published: Feb. 15, 2024

Language: Английский

Citations

31
Steatotic liver disease DOI
Mads Israelsen, Sven Francque, Emmanuel Tsochatzis

et al.

The Lancet, Journal Year: 2024, Volume and Issue: 404(10464), P. 1761 - 1778

Published: Nov. 1, 2024

Language: Английский

Citations

30
Metabolic Dysfunction and Alcohol-related Liver Disease (MetALD): Position statement by an expert panel on alcohol-related liver disease DOI
Juan Pablo Arab, Luis Antonio Díaz, Jürgen Rehm

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

23
Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review DOI Creative Commons
Basma Hossam Abdelmonem,

Noha M. Abdelaal,

Eman K. E. Anwer

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1467 - 1467

Published: July 2, 2024

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families the human genome, which CYP1, CYP2, and CYP3 are prominent. Beyond drug CYP metabolize endogenous compounds such as lipids, proteins, hormones to maintain physiological homeostasis. Thus, dysregulation CYP450 can lead different endocrine disorders. Moreover, significantly contribute fatty acid cholesterol synthesis, bile biosynthesis, impacting cellular physiology disease pathogenesis. Their diverse functions emphasize their therapeutic potential managing hypercholesterolemia neurodegenerative diseases. Additionally, implicated onset development illnesses cancer, influencing chemotherapy outcomes. Assessment enzyme expression activity aids evaluating liver health state differentiating between diseases, guiding decisions, optimizing efficacy. Understanding roles clinical effect genetic polymorphisms crucial for developing personalized strategies enhancing responses patient populations.

Language: Английский

Citations

20