Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease

Zhu, Cheng; Huai, Qian; Zhang, Xu; Dai, Hanren; Li, Xiaolei; Wang, Hua

doi:10.7150/ijbs.78525

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Theranostics

International Journal of Medical Sciences

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Journal of Cancer

Journal of Genomics

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Int J Biol Sci 2023; 19(1):311-330. doi:10.7150/ijbs.78525 This issue Cite

Review

Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease

Cheng Zhu^1*, Qian Huai^1*, Xu Zhang¹, Hanren Dai¹, Xiaolei Li^1✉, Hua Wang^1,2✉

1. Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
2. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China.
^*These authors have contributed equally to this work and share first authorship.

Citation:

Zhu C, Huai Q, Zhang X, Dai H, Li X, Wang H. Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease. Int J Biol Sci 2023; 19(1):311-330. doi:10.7150/ijbs.78525. https://www.ijbs.com/v19p0311.htm

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Abstract

Non-alcoholic fatty liver disease (NAFLD), as one of the main causes of chronic liver disease worldwide, encompasses a spectrum of liver conditions that are not caused by other etiology, such as overt alcohol consumption, from simple steatosis to more aggressive non-alcoholic steatohepatitis (NASH) that involves liver inflammation and fibrosis, and to the lethal cirrhosis that may result in liver cancer and liver failure. The molecular mechanisms governing the transition from steatosis to NASH remain not fully understood, but the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis, which also correlate with disease progression. With the tremendous advancement in the field of lipidomics in last two decades, a better understanding of the specific role of sphingolipids in fatty liver disease has taken shape. Among the numerous lipid subtypes that accumulate, ceramides are particularly impactful. On the one hand, excessive ceramides deposition in the liver cause hepatic steatosis. On the other hand, ceramides as lipotoxic lipid have significant effects on hepatic inflammation, apoptosis and insulin resistance that contribute to NAFLD. In this review, we summarize and evaluate current understanding of the multiple roles of ceramides in the onset of fatty liver disease and the pathogenic mechanisms underlying their effects, and we also discuss recent advances and challenges in pharmacological interventions targeting ceramide metabolism for the treatment of NAFLD.

Keywords: Ceramides, NAFLD, NASH, lipid metabolism, therapeutics.

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APA

Zhu, C., Huai, Q., Zhang, X., Dai, H., Li, X., Wang, H. (2023). Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease. International Journal of Biological Sciences, 19(1), 311-330. https://doi.org/10.7150/ijbs.78525.

ACS

Zhu, C.; Huai, Q.; Zhang, X.; Dai, H.; Li, X.; Wang, H. Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease. Int. J. Biol. Sci. 2023, 19 (1), 311-330. DOI: 10.7150/ijbs.78525.

NLM

CSE

Zhu C, Huai Q, Zhang X, Dai H, Li X, Wang H. 2023. Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease. Int J Biol Sci. 19(1):311-330.

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