Energy metabolism: An emerging therapeutic frontier in liver fibrosis
Liver fibrosis is a progressive response to chronic liver diseases characterized by a wound-healing process that leads to the accumulation of fibrillary extracellular matrix (ECM) proteins in and around the liver tissue. If left untreated, liver fibrosis can advance to cirrhosis and ultimately resul...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268125001206 |
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| author | Iram Irshad Saleh A Alqahtani Kenichi Ikejima Ming-Lung Yu Manuel Romero-Gomez Mohammed Eslam |
| author_facet | Iram Irshad Saleh A Alqahtani Kenichi Ikejima Ming-Lung Yu Manuel Romero-Gomez Mohammed Eslam |
| author_sort | Iram Irshad |
| collection | DOAJ |
| description | Liver fibrosis is a progressive response to chronic liver diseases characterized by a wound-healing process that leads to the accumulation of fibrillary extracellular matrix (ECM) proteins in and around the liver tissue. If left untreated, liver fibrosis can advance to cirrhosis and ultimately result in liver failure. Although there have been significant advancements in understanding the molecular mechanisms involved in liver fibrosis, effective therapeutic strategies to reverse or halt the condition remain limited. Recent research has underscored the critical role of energy metabolism in the initiation and progression of liver fibrosis. In response to liver injury, hepatic cells undergo metabolic reprogramming to meet the energy demands of myofibroblasts. This reprogramming involves various metabolic changes, including mitochondrial dysfunction, alterations in cellular bioenergetics, shifts in glycolysis and oxidative phosphorylation, as well as changes in lipid metabolism. These modifications can disrupt cellular energy homeostasis and increase energy release, activating hepatic cells, primarily hepatic stellate cells (HSCs). Activated HSCs then stimulate fibrogenic pathways, leading to the accumulation of ECM proteins in the liver, which exacerbates the progression of fibrosis.This review aims to explore the emerging connection between energy metabolism and liver fibrosis, focusing on the metabolic alterations and molecular mechanisms that drive this condition. We also examine the therapeutic implications of modulating energy metabolism to reduce energy release and mitigate liver fibrosis. Altering energy metabolism to decrease energy release may represent a promising approach for treating liver fibrosis and chronic liver diseases. |
| format | Article |
| id | doaj-art-4f4d41d988b54f269afeb8e7803d9554 |
| institution | DOAJ |
| issn | 1665-2681 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj-art-4f4d41d988b54f269afeb8e7803d95542025-08-20T03:18:23ZengElsevierAnnals of Hepatology1665-26812025-01-0130110189610.1016/j.aohep.2025.101896Energy metabolism: An emerging therapeutic frontier in liver fibrosisIram Irshad0Saleh A Alqahtani1Kenichi Ikejima2Ming-Lung Yu3Manuel Romero-Gomez4Mohammed Eslam5Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, AustraliaLiver, Digestive, & Lifestyle Health Research Section, and Organ Transplant Center of Excellence, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USADepartment of Gastroenterology, Juntendo University School of Medicine, JapanSchool of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital; College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, TaiwanDigestive Diseases Department and Ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, SpainStorr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia; Corresponding author.Liver fibrosis is a progressive response to chronic liver diseases characterized by a wound-healing process that leads to the accumulation of fibrillary extracellular matrix (ECM) proteins in and around the liver tissue. If left untreated, liver fibrosis can advance to cirrhosis and ultimately result in liver failure. Although there have been significant advancements in understanding the molecular mechanisms involved in liver fibrosis, effective therapeutic strategies to reverse or halt the condition remain limited. Recent research has underscored the critical role of energy metabolism in the initiation and progression of liver fibrosis. In response to liver injury, hepatic cells undergo metabolic reprogramming to meet the energy demands of myofibroblasts. This reprogramming involves various metabolic changes, including mitochondrial dysfunction, alterations in cellular bioenergetics, shifts in glycolysis and oxidative phosphorylation, as well as changes in lipid metabolism. These modifications can disrupt cellular energy homeostasis and increase energy release, activating hepatic cells, primarily hepatic stellate cells (HSCs). Activated HSCs then stimulate fibrogenic pathways, leading to the accumulation of ECM proteins in the liver, which exacerbates the progression of fibrosis.This review aims to explore the emerging connection between energy metabolism and liver fibrosis, focusing on the metabolic alterations and molecular mechanisms that drive this condition. We also examine the therapeutic implications of modulating energy metabolism to reduce energy release and mitigate liver fibrosis. Altering energy metabolism to decrease energy release may represent a promising approach for treating liver fibrosis and chronic liver diseases.http://www.sciencedirect.com/science/article/pii/S1665268125001206Liver fibrosisEnergy metabolismMetabolic reprogrammingHSCsROSAutophagy |
| spellingShingle | Iram Irshad Saleh A Alqahtani Kenichi Ikejima Ming-Lung Yu Manuel Romero-Gomez Mohammed Eslam Energy metabolism: An emerging therapeutic frontier in liver fibrosis Annals of Hepatology Liver fibrosis Energy metabolism Metabolic reprogramming HSCs ROS Autophagy |
| title | Energy metabolism: An emerging therapeutic frontier in liver fibrosis |
| title_full | Energy metabolism: An emerging therapeutic frontier in liver fibrosis |
| title_fullStr | Energy metabolism: An emerging therapeutic frontier in liver fibrosis |
| title_full_unstemmed | Energy metabolism: An emerging therapeutic frontier in liver fibrosis |
| title_short | Energy metabolism: An emerging therapeutic frontier in liver fibrosis |
| title_sort | energy metabolism an emerging therapeutic frontier in liver fibrosis |
| topic | Liver fibrosis Energy metabolism Metabolic reprogramming HSCs ROS Autophagy |
| url | http://www.sciencedirect.com/science/article/pii/S1665268125001206 |
| work_keys_str_mv | AT iramirshad energymetabolismanemergingtherapeuticfrontierinliverfibrosis AT salehaalqahtani energymetabolismanemergingtherapeuticfrontierinliverfibrosis AT kenichiikejima energymetabolismanemergingtherapeuticfrontierinliverfibrosis AT minglungyu energymetabolismanemergingtherapeuticfrontierinliverfibrosis AT manuelromerogomez energymetabolismanemergingtherapeuticfrontierinliverfibrosis AT mohammedeslam energymetabolismanemergingtherapeuticfrontierinliverfibrosis |