Scp-2/Scp-x ablation in Fabp1 null mice differentially impacts hepatic endocannabinoid level depending on dietary fat
Autor: | Friedhelm Schroeder, Mikhail Y. Golovko, Ann B. Kier, Gregory G. Martin, Danilo Landrock, Drew R. Seeger, Sarah Chung, Sherrelle Milligan, Eric J. Murphy, Avery L. McIntosh, Lawrence J. Dangott |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Null mice medicine.medical_specialty Biophysics Diet High-Fat Fatty Acid-Binding Proteins Biochemistry Article Fatty acid-binding protein Mice 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Glycerol Animals Molecular Biology Mice Knockout 030102 biochemistry & molecular biology Chemistry Fatty liver High fat diet medicine.disease Dietary Fats Endocannabinoid system Sterol Mice Inbred C57BL 030104 developmental biology Endocrinology Liver Female lipids (amino acids peptides and proteins) Arachidonic acid Carrier Proteins Gene Deletion Endocannabinoids |
Zdroj: | Archives of Biochemistry and Biophysics. 650:93-102 |
ISSN: | 0003-9861 |
DOI: | 10.1016/j.abb.2018.05.013 |
Popis: | 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. |
Databáze: | OpenAIRE |
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