Dysregulation of sphingolipid metabolism in liver fibrosis

Abstract

The dysregulation of sphingolipid metabolism emerges as a pivotal factor in the development and progression of liver fibrosis, a condition marked by the overproduction and buildup of extracellular matrix proteins that can lead to liver cirrhosis and failure. Sphingolipids, a diverse class of lipids essential for cellular structure and signaling, are integral to numerous biological functions such as cellular proliferation, morphological differentiation, and programmed cell death. In the context of liver fibrosis, changes in sphingolipid metabolism have been associated with the activation of hepatic stellate cells, the primary cells responsible for fibrogenesis in the liver. These metabolic disruptions lead to an imbalance between profibrotic and antifibrotic sphingolipids, notably sphingosine-1-phosphate and ceramide, contributing to the pathophysiological mechanisms that drive fibrosis. The intricate relationship between sphingolipid metabolism and fibrotic pathways underscores the potential of targeting sphingolipid metabolic enzymes and receptors as therapeutic strategies to mitigate liver fibrosis. The core of this review delves into how disruptions in sphingolipid metabolism contribute to liver fibrosis, exploring biomarkers and potential therapeutic targets. Challenges in research and future directions for comprehensively understanding sphingolipid roles in liver fibrosis are discussed, aiming to open new pathways for therapeutic intervention.

Keywords

Sphingolipids / liver fibrosis / SphK / S1P

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