Cited by 427Liver physiology and pathologyLiver Disease Diagnosis and TreatmentDrug-Induced Hepatotoxicity and Protection

The Power of Plasticity—Metabolic Regulation of Hepatic Stellate Cells

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Trivedi, Parth, Wang, Shuang, Friedman, Scott L.·2021·Cell Metabolism

Abstract

Hepatic stellate cells (HSCs) are resident non-parenchymal liver pericytes whose plasticity enables them to regulate a remarkable range of physiologic and pathologic responses. To support their functions in health and disease, HSCs engage pathways regulating carbohydrate, mitochondrial, lipid, and retinoid homeostasis. In chronic liver injury, HSCs drive hepatic fibrosis and are implicated in inflammation and cancer. To do so, the cells activate, or transdifferentiate, from a quiescent state into proliferative, motile myofibroblasts that secrete extracellular matrix, which demands rapid adaptation to meet a heightened energy need. Adaptations include reprogramming of central carbon metabolism, enhanced mitochondrial number and activity, endoplasmic reticulum stress, and liberation of free fatty acids through autophagy-dependent hydrolysis of retinyl esters that are stored in cytoplasmic droplets. As an archetype for pericytes in other tissues, recognition of the HSC's metabolic drivers and vulnerabilities offer the potential to target these pathways therapeutically to enhance parenchymal growth and modulate repair.

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Crossref · 10.1016/j.cmet.2020.10.026

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  • Activation of HSCs in culture is associated with increased glycolysis, lipolysis, and glutaminolysis, which provide energy for this energy-intensive process.

    “In particular, the activation of HSCs in culture is associated with increased glycolysis, lipolysis, and glutaminolysis, which provide the energy needed for this energy-intensive process (as detailed in (182)).”

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Authors
Trivedi, P., Wang, S., & Friedman, S. L.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Friedman, Scott L.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2021-02
Volume
33
Issue
2
Pages
242-257
ISSN
1550-4131 (ISSN-L)
OpenAlex
W3110189951
Cited by
427
References
195
Citations by year
2026: 86 · 2025: 105 · 2024: 81 · 2023: 78 · 2022: 50 · 2021: 27
FWCI
5.20
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK56621)
  • American Gastroenterological Association (AGA2020-13-03)
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
hepatic stellate cells, cellular plasticity, metabolic regulation, liver fibrosis, chronic liver injury, myofibroblast transdifferentiation, central carbon metabolism, mitochondrial metabolism, endoplasmic reticulum stress, autophagy, free fatty acids, extracellular matrix secretion, liver inflammation, liver cancer, pericytes
MeSH terms
Cell Plasticity, Animals, Humans, Hepatic Stellate Cells

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