Anti-FABP1 monoclonal antibody, clone FQS6906(3)

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.

The diagnostic process of disease detection and the disease management after therapy has been initiated differ from one disease to the next. The process of diagnosing kala-azar has recently been simplified. The time-consuming pathological exam that was formerly needed has been replaced by a convenient blood test. But once treatment has begun, the monitoring of disease activity still relies on clinical findings and laboratory data in endemic areas. In this chapter, we propose the use of the urinary biomarker, fatty-acid-binding protein 1 (FABP1), for monitoring kala-azar disease activity and drug-induced side effects. The FABP1 assay, developed as an enzyme-linked immunosorbent assay, was developed in the form of an irnmunochromatography (dipstick) urine test in our project for use in areas with a high concentration of kala-azar infection. We expect that the FABP1 dipstick test will prove invaluable as a triage tool and for monitoring the severity of the disease. In addition, we discuss the potential usefulness of urinary interleukin-18, a biomarker for acute kidney injury, in monitoring kala-azar activity. Further studies of this and other recently discovered urinary biomarkers are needed.