Commentary 10.1172/JCI154147

Controversies surrounding peripheral cannabinoid receptor 1 in fatty liver disease

Beste Mutlu1,2 and Pere Puigserver1,2

1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

2Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.

Address correspondence to: Pere Puigserver or Beste Mutlu, Dana-Farber Cancer Institute, 360 Brookline Ave., LC 6213, Boston, Massachusetts 02115-5450, USA. Phone: 617.582.7977; Email: pere_puigserver@dfci.harvard.edu (PP); Email: beste_mutlu@dfci.harvard.edu (BM).

Find articles by Mutlu, B. in: JCI | PubMed | Google Scholar |

1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

2Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.

Address correspondence to: Pere Puigserver or Beste Mutlu, Dana-Farber Cancer Institute, 360 Brookline Ave., LC 6213, Boston, Massachusetts 02115-5450, USA. Phone: 617.582.7977; Email: pere_puigserver@dfci.harvard.edu (PP); Email: beste_mutlu@dfci.harvard.edu (BM).

Find articles by Puigserver, P. in: JCI | PubMed | Google Scholar

Published November 15, 2021 - More info

Published in Volume 131, Issue 22 on November 15, 2021
J Clin Invest. 2021;131(22):e154147. https://doi.org/10.1172/JCI154147.
© 2021 American Society for Clinical Investigation
Published November 15, 2021 - Version history
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Cannabinoid receptor 1 (CB-1) antagonists are potential candidates for treating obesity and metabolic complications. Despite clear metabolic benefits, unwanted side effects in the brain pose issues for patients. With the hope of overcoming this obstacle, CB-1 in peripheral tissues has become a potential drug target. Previous studies had suggested that liver CB-1 would be an excellent target to prevent development of nonalcoholic steatohepatitis (NAFLD). However, in this issue of the JCI, Wang et al. showed that CB-1 was barely detectable in the liver and deletion of CB-1 in hepatocytes provided no metabolic benefits against NAFLD. These contradictory results raise substantial concerns about the potential benefits of peripheral CB-1 blockers against NAFLD.

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