The AAPS Journal

, Volume 12, Issue 2, pp 233–237 | Cite as

Role of Cannabinoids in the Development of Fatty Liver (Steatosis)

Review Article Theme: NIDA Symposium: Drugs of Abuse: Drug Development and Cannabinoids

Abstract

Emerging evidence suggests that cannabinoids play an important role in the modulation of fatty liver, which appears to be mediated via activation of cannabinoid receptors. Steatogenic agents such as ethanol and high-fat diet can upregulate the activity of cannabinoid 1 (CB1) receptors via increasing synthesis of endocannabinoids, 2-arachidonoylglycerol, and anandamide. CB1 receptors can also be upregulated by obesity. CB1 receptor activation results in upregulation of lipogenic transcription factor, sterol regulatory element-binding protein 1c and its target enzymes, acetyl-CoA carboxylase-1, and fatty acid synthase and concomitantly, downregulation of carnitine palmitoyltransferase-1. This leads to increased de novo fatty acid synthesis as well as decreased fatty acid oxidation, culminating into the development of fatty liver. High-fat diet, in addition to CB1 receptor activation, appears to activate CB2 receptors that may also contribute to fatty liver. In non-alcoholic fatty liver disease, CB2 receptor activation is associated with the development of fatty liver. Cannabis smoking can increase the severity of fatty liver in hepatitis C patients although the precise mechanism is unknown. As the mechanisms involved in endocannabinoid receptor signaling are being increasingly well understood and the biosynthetic regulatory elements elucidated, these present good opportunity for the pharmaceutical scientists to design drugs to treat liver diseases, including steatosis, based on the cannabinoids, endocannabinoids, and related templates.

Key words

cannabinoids CB1 receptor CB2 receptor fatty liver 

Notes

Acknowledgement

Authors are thankful to Dr. George Kunos for his valuable suggestions in the preparation of this manuscript.

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Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  • Vishnudutt Purohit
    • 1
  • Rao Rapaka
    • 1
  • David Shurtleff
    • 2
  1. 1.Chemistry and Physiological Systems Research Branch, Division of Basic Neuroscience & Behavioral Research, National Institute on Drug Abuse (NIDA)National Institutes of HealthBethesdaUSA
  2. 2.Division of Basic Neuroscience & Behavioral Research, National Institute on Drug Abuse (NIDA)National Institutes of HealthBethesdaUSA

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