Leptin Mediated Fibrogenesis in Hepatic Stellate Cells
Summary
Leptin, a hormone predominantly secreted by adipose tissue, has emerged as a central driver of liver fibrogenesis through its direct actions on hepatic stellate cells (HSCs). In the quiescent state, HSCs store vitamin A and regulate the extracellular matrix. Upon liver injury, leptin engages its long-form receptor (ObR) on HSCs, triggering JAK/STAT, PI3K/Akt and MAPK cascades. This signalling network shifts HSCs from a lipid-rich phenotype towards a contractile, collagen-secreting myofibroblast state. Concomitant activation of developmental pathways such as Hedgehog further reinforces epithelial-to-mesenchymal transition and matrix deposition. Leptin-driven changes include upregulation of tissue inhibitor of metalloproteinase-1, downregulation of quiescence factors such as PPARγ and sterol regulatory element-binding protein-1c, and induction of transcription factors like GATA3. Collectively, these events promote accumulation of type I collagen and other matrix proteins, impair matrix turnover and perpetuate chronic fibrosis. Understanding the molecular interplay between leptin signalling and HSC activation is critical for identifying novel anti-fibrotic interventions in conditions such as non-alcoholic steatohepatitis, viral hepatitis and alcohol-related liver disease.
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Leptin Mediated Fibrogenesis in Hepatic Stellate Cells publication trend
The graph below shows the total number of articles in leptin mediated fibrogenesis in hepatic stellate cells across all publications each year (not limited to Nature Index journals).
Technical terms
Leptin: Adipose-derived hormone that regulates energy balance and exerts profibrogenic effects in the liver.
Hepatic stellate cell (HSC): Liver pericytes that trans-differentiate into collagen-producing myofibroblasts during injury.
Fibrogenesis: Process of scar tissue formation involving accumulation of collagen and extracellular matrix in response to injury.
Epithelial-to-mesenchymal transition (EMT): Cellular programme by which cells acquire migratory, fibroblast-like properties.
Hedgehog signalling pathway: A developmental cascade that, when reactivated in HSCs, promotes fibrogenic trans-differentiation.
PPARγ: Nuclear receptor that maintains HSC quiescence and whose downregulation favours activation.
SREBP-1c: Lipogenic transcription factor that supports the quiescent phenotype of HSCs and is downregulated by profibrotic signals.
References
- GATA binding protein 3 is correlated with leptin regulation of PPARγ1 in hepatic stellate cells. Journal of Cellular and Molecular Medicine (2016).
- Leptin Promotes the Myofibroblastic Phenotype in Hepatic Stellate Cells by Activating the Hedgehog Pathway. Journal of Biological Chemistry (2010).
- Leptin Stimulates Tissue Inhibitor of Metalloproteinase-1 in Human Hepatic Stellate Cells RESPECTIVE ROLES OF THE JAK/STAT AND JAK-MEDIATED H2O2-DEPENDENT MAPK PATHWAYS*. Journal of Biological Chemistry (2003).
- Mechanistic insights into the effects of SREBP1c on hepatic stellate cell and liver fibrosis. Journal of Cellular and Molecular Medicine (2020).
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