9-Tetrahydrocannabinol induces endocannabinoid accumulation in mouse hepatocytes: antagonism by Fabp1 gene ablation. Academic Article uri icon

abstract

  • Phytocannabinoids, such as 9-tetrahydrocannabinol (THC), bind and activate cannabinoid (CB) receptors, thereby "piggy-backing" on the same pathway's endogenous endocannabinoids (ECs). The recent discovery that liver fatty acid binding protein-1 (FABP1) is the major cytosolic "chaperone" protein with high affinity for both 9-THC and ECs suggests that 9-THC may alter hepatic EC levels. Therefore, the impact of 9-THC or EC treatment on the levels of endogenous ECs, such as N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), was examined in cultured primary mouse hepatocytes from WT and Fabp1 gene-ablated (LKO) mice. 9-THC alone or 2-AG alone significantly increased AEA and especially 2-AG levels in WT hepatocytes. LKO alone markedly increased AEA and 2-AG levels. However, LKO blocked/diminished the ability of 9-THC to further increase both AEA and 2-AG. In contrast, LKO potentiated the ability of exogenous 2-AG to increase the hepatocyte level of AEA and 2-AG. These and other data suggest that 9-THC increases hepatocyte EC levels, at least in part, by upregulating endogenous AEA and 2-AG levels. This may arise from 9-THC competing with AEA and 2-AG binding to FABP1, thereby decreasing targeting of bound AEA and 2-AG to the degradative enzymes, fatty acid amide hydrolase and monoacylglyceride lipase, to decrease hydrolysis within hepatocytes.

published proceedings

  • J Lipid Res

altmetric score

  • 3.35

author list (cited authors)

  • McIntosh, A. L., Martin, G. G., Huang, H., Landrock, D., Kier, A. B., & Schroeder, F.

citation count

  • 13

complete list of authors

  • McIntosh, Avery L||Martin, Gregory G||Huang, Huan||Landrock, Danilo||Kier, Ann B||Schroeder, Friedhelm

publication date

  • April 2018