Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8288527 | Archives of Biochemistry and Biophysics | 2018 | 10 Pages |
Abstract
Dysregulation of the hepatic endocannabinoid (EC) system and high fat diet (HFD) are associated with non-alcoholic fatty liver disease. Liver cytosol contains high levels of two novel endocannabinoid binding proteins-liver fatty acid binding protein (FABP1) and sterol carrier protein-2 (SCP-2). While Fabp1 gene ablation significantly increases hepatic levels of arachidonic acid (ARA)-containing EC and sex-dependent response to pair-fed high fat diet (HFD), the presence of SCP-2 complicates interpretation. These issues were addressed by ablating Scp-2/Scp-x in Fabp1 null mice (TKO). In control-fed mice, TKO increased hepatic levels of arachidonoylethanolamide (AEA) in both sexes. HFD impacted hepatic EC levels by decreasing AEA in TKO females and decreasing 2-arachidonoyl glycerol (2-AG) in WT of both sexes. Only TKO males on HFD had increased hepatic 2-AG levels. Hepatic ARA levels were decreased in control-fed TKO of both sexes. Changes in hepatic AEA/2-AG levels were not associated with altered amounts of hepatic proteins involved in AEA/2-AG synthesis or degradation. These findings suggested that ablation of the Scp-2/Scp-x gene in Fabp1 null mice exacerbated hepatic EC accumulation and antagonized the impact of HFD on hepatic EC levels-suggesting both proteins play important roles in regulating the hepatic EC system.
Keywords
palmitoylethanolamideFABP1DAGLαFAAHLKO2-arachidonoyl glycerol2-monoacylglycerolCB1maglNAEhsp702-AGoleoylethanolamideN-acylethanolamidesNAAASCP-2SCP-xLCFADHEAPEAAEANAFLD2-OGHFD, high fat dietLC/MSOEATKOendocannabinoidSterol carrier protein-2Arachidonic acidFatty acid amide hydrolaselong chain fatty acidnon-alcohol fatty liver diseaseGene ablationARADHAHigh fat dietMouseNAPEheat shock protein 70LiverLiquid chromatography/mass spectrometrycannabinoid receptor-1
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Authors
Gregory G. Martin, Drew R. Seeger, Avery L. McIntosh, Sarah Chung, Sherrelle Milligan, Danilo Landrock, Lawrence J. Dangott, Mikhail Y. Golovko, Eric J. Murphy, Ann B. Kier, Friedhelm Schroeder,