Endocannabinoids (EC) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, 5, 7) serve this function in brain, relatively little is known about how such hydrophobic EC and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1, L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA—suggesting that FABP1 may also bind ARA-derived ECs (AEA, 2-AG). Indeed, FABP1 bound EC with high affinity as shown by displacement of FABP1-bound fluorescent ligands and by quenching of FABP1 intrinsic tyrosine fluorescence. FABP1 also had high affinity for most non-ARA containing ECs, FABP1 inhibitors, EC uptake/hydrolysis inhibitors, phytocannabinoids, and less so synthetic cannabinoid receptor (CBR) agonists and antagonists. Physiological impact was examined with liver from wild-type (WT) versus FABP1 gene ablated (LKO) male mice. As shown by LC/MS, FABP1 gene ablation significantly increased hepatic levels of AEA, 2-AG, and 2-OG. These increases were not due to increased protein levels of EC synthetic enzymes (NAPEPLD, DAGL) or decreased level of EC degradative enzyme (FAAH), but correlated with complete loss of FABP1, decreased SCP2 (8-fold less prevalent than FABP1, but also binds ECs), and decreased degradative enzymes (NAAA, MAGL). These data indicated that FABP1 is not only the most prominent endocannabinoid and cannabinoid binding protein, but also impacts hepatic endocannabinoid levels.

The North China Craton (NCC) hosts numerous gold deposits and is known as the most gold-productive region of China. The gold deposits were mostly formed within a few million years in the Early Cretaceous (130-120 Ma), coeval with widespread occurrences of bimodal magmatism, rift basins and metamorphic core complexes that marked the peak of lithospheric thinning and destruction of the NCC. Stable isotope data and geological evidence indicate that ore-forming fluids and other components were largely exsolved from cooling magma and/or derived from mantle degassing during the period of lithospheric extension. Gold mineralization in the NCC contrasts strikingly with that of other cratons where gold ore-forming fluids were sourced mostly from metamorphic devolatization in compressional or transpressional regimes. In this paper, we present a summary and discussion on time-space distribution and ore genesis of gold deposits in the NCC in the context of the timing, spatial variation, and decratonic processes. Compared with orogenic gold deposits in other cratonic blocks, the Early Cretaceous gold deposits in the NCC are quite distinct in that they were deposited from magma-derived fluids under extensional settings and associated closely with destruction of cratonic lithosphere. We argue that Early Cretaceous gold deposits in the NCC cannot be classified as orogenic gold deposits as previously suggested, rather, they are a new type of gold deposits, termed as "decratonic gold deposits" in this study. The westward subduction of the paleo-West Pacific plate (the Izanagi plate) beneath the eastern China continent gave rise to an optimal tectonic setting for large-scale gold mineralization in the Early Cretaceous. Dehydration of the subducted and stagnant slab in the mantle transition zone led to continuous hydration and considerable metasomatism of the mantle wedge beneath the NCC. As a consequence, the refractory mantle became oxidized and highly enriched in large ion lithophile elements and chalcophile elements (e.g., Cu, Au, Ag and Te). Partial melting of such a mantle would have produced voluminous hydrous, Au-and S-bearing basaltic magma, which, together with crust-derived melts induced by underplating of basaltic magma, served as an important source for ore-forming fluids. It is suggested that the Eocene Carlin-type gold deposits in Nevada, occurring geologically in the deformed western margin of the North America Craton, are comparable with the Early Cretaceous gold deposits of the NCC because they share similar tectonic settings and auriferous fluids. The NCC gold deposits are characterized by gold-bearing quartz veins in the Archean amphibolite facies rocks, whereas the Nevada gold deposits are featured by fine-grained sulfide dissemination in Paleozoic marine sedimentary rocks. Their main differences in gold mineralization are the different host rocks, ore-controlling structures, and ore-forming depth. The similar tectonic setting and ore-forming fluid source, however, indicate that the Carlin-type gold deposits in ...

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The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear—especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α, (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human SNP (26–38% minor allele frequency and 8.3±1.9% homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant’s impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system on hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.

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