Sterol Carrier Protein-2/Sterol Carrier Protein-x/Fatty Acid Binding Protein-1 Ablation Impacts Response of Brain Endocannabinoid to High-Fat Diet
Autor: | Sarah Chung, Danilo Landrock, Sherrelle Milligan, Drew R. Seeger, Friedhelm Schroeder, Mikhail Y. Golovko, Eric J. Murphy, Lawrence J. Dangott, Avery L. McIntosh, Gregory G. Martin, Ann B. Kier |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Diet High-Fat Fatty Acid-Binding Proteins Biochemistry Fatty acid-binding protein 03 medical and health sciences chemistry.chemical_compound Mice Fatty acid binding Internal medicine medicine Animals chemistry.chemical_classification Mice Knockout 030109 nutrition & dietetics Chemistry Organic Chemistry food and beverages Brain Cell Biology biochemical phenomena metabolism and nutrition Endocannabinoid system Sterol carbohydrates (lipids) Mice Inbred C57BL Cytosol 030104 developmental biology Sterol carrier protein Enzyme Endocrinology lipids (amino acids peptides and proteins) Arachidonic acid Female Carrier Proteins Endocannabinoids |
Zdroj: | LipidsReferences. 54(10) |
ISSN: | 1558-9307 |
Popis: | Brain endocannabinoids (EC) such as arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) primarily originate from serum arachidonic acid (ARA), whose level is regulated in part by a cytosolic ARA-binding protein, that is, liver fatty acid binding protein-1 (FABP1), not expressed in the brain. Ablation of the Fabp1 gene (LKO) increases brain AEA and 2-AG by decreasing hepatic uptake of ARA to increase serum ARA, thereby increasing ARA availability for uptake by the brain. The brain also expresses sterol carrier protein-2 (SCP-2), which is also a cytosolic ARA-binding protein. To further resolve the role of SCP-2 independent of FABP1, mice ablated in the Scp-2/Scp-x gene (DKO) were crossed with mice ablated in the Fabp1 gene (LKO) mice to generate triple knock out (TKO) mice. TKO impaired the ability of LKO to increase brain AEA and 2-AG. While a high-fat diet (HFD) alone increased brain AEA, TKO impaired this effect. Overall, these TKO-induced blocks were not attributable to altered expression of brain proteins in ARA uptake, AEA/2-AG synthesis, or AEA/2-AG degrading enzymes. Instead, TKO reduced serum levels of free ARA and/or total ARA and thereby decreased ARA availability for uptake to the brain and downstream synthesis of AEA and 2-AG therein. In summary, Scp-2/Scp-x gene ablation in Fabp1 null (LKO) mice antagonized the impact of LKO and HFD on brain ARA and, subsequently, EC levels. Thus, both FABP1 and SCP-2 participate in regulating the EC system in the brain. |
Databáze: | OpenAIRE |
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