A new study demonstrates a novel role for an endocannabinoid in promoting hepatocyte steatosis. The study describes a mode of bidirectional communication between the alcohol-injured hepatocyte and the glutamate-activated hepatic stellate cell. This intercellular communication represents a novel targetable pathogenic mechanism that could lead to new strategies to prevent fatty liver disease progression to cirrhosis.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Asrani, S. K. et al. Burden of liver diseases in the world. J. Hepatol. 70, 151–171 (2019).
McPherson, S. et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J. Hepatol. 62, 1148–1155 (2015).
Parker, R. et al. Natural history of histologically proven alcohol-related liver disease: a systematic review. J. Hepatol. 71, 586–593 (2019).
Louvet, A. & Mathurin, P. Alcoholic liver disease: mechanisms of injury and targeted treatment. Nat. Rev. Gastroenterol. Hepatol. 12, 231–242 (2015).
Dam-Larsen, S. et al. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut. 53, 750–755 (2004).
Choi, W. M. et al. Glutamate signaling in hepatic stellate cells drives alcoholic steatosis. Cell Metab. https://doi.org/10.1016/j.cmet.2019.08.001 (2019).
Spooren, W. et al. Insight into the function of group I and group II metabotropic glutamate (mGlu) receptors: behavioural characterization and implications for the treatment of CNS disorders. Behav. Pharmacol. 14, 257–277 (2003).
Caraceni, P. et al. The endocannabinoid system and liver diseases. J. Neuroendocrinol. 20, 47–52 (2008).
Nguyen, T. et al. Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: current approaches for therapeutics development. Curr. Top. Med. Chem. 19, 1418–1435 (2019).
Godlewski, G. et al. Targeting peripheral CB1 receptors reduces ethanol intake via a gut-brain axis. Cell Metab. 29, 1320–1333 (2019).
R.B. is supported by NIH/NIAAA grants AA026972, AA026978 and AA026264, and by NIH/NIDDK grant P30DK120531.
The authors declare no competing interests.
About this article
Cite this article
Argemi, J., Bataller, R. Hepatocyte–stellate cell synapse in alcohol-induced steatosis: another role for endocannabinoids. Nat Rev Gastroenterol Hepatol 17, 5–6 (2020). https://doi.org/10.1038/s41575-019-0233-8
Pharmacology, Clinical Effects, and Therapeutic Potential of Cannabinoids for Gastrointestinal and Liver Diseases
Clinical Gastroenterology and Hepatology (2020)