Disease relevance of Slc27a5

• CONCLUSIONS: Our findings reveal an important role for FATP5 in bile acid conjugation in vivo and an unexpected function in body weight homeostasis, which will require further analysis [1].
• Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity [1].
• Despite normal fat absorption, FATP5 deletion mice failed to gain weight on a high-fat diet because of both decreased food intake and increased energy expenditure [1].
• Tissue inflammation, goblet cell hyperplasia, and IL-4, IL-5, and IL-13 levels in BAL fluid were significantly reduced in fB-/- mice compared with C4-/- and WT mice [2].
• BAL 13, the only lymphoma of the Lyt-1+,2- phenotype examined, was completely resistant to DCF in vivo and in vitro [3].

High impact information on Slc27a5

• BCL1 cells MOPC104E (murine myeloma cell line) expressed IL-5-R, whereas BAL [4].
• CONCLUSIONS: Our findings support the hypothesis that efficient hepatocellular uptake of LCFAs, and thus liver lipid homeostasis in general, is largely a protein-mediated process requiring FATP5 [5].
• Here, we investigate its role in bile acid metabolism and body weight homeostasis in vivo by using a novel FATP5 knockout mouse model [1].
• Conversely, FATP5 deletion significantly reduced LCFA uptake by hepatocytes isolated from FATP5 knockout animals [5].
• Furthermore, we created a FATP5 knockout mouse model and characterized changes in hepatic lipid metabolism (this report) and bile metabolism (the accompanying report by Hubbard et al) [5].

Chemical compound and disease context of Slc27a5

• Remarkably, anti-IL-17 mAb significantly enhanced IL-5 levels in both BAL fluid and serum, and aggravated allergen-induced bronchial eosinophilia [6].
• British antilewisite (2,3-dimercaptopropanol; BAL) has long been used as an arsenic antidote, but its therapeutic efficacy is limited by its inherent toxicity [7].
• Whereas 5 ppm NO2 elicited no pathological changes, inhalation of 25 ppm NO2 alone induced acute lung injury, which peaked after 3 days and was characterized by increases in protein, LDH, and neutrophils recovered by BAL, as well as lesions within terminal bronchioles [8].
• No other significant protective effects against arsenite toxicity were seen due to BAL; however, concurrent BAL treatment on Day 9 appeared to result in decreased fetal mortality and a decline in skeletal malformations [9].
• RESULTS: The 10-day animals developed allergic airway disease, characterized by BAL eosinophilia, histologic airway inflammation and mucus secretion, methacholine hyperresponsiveness, and OVA-specific IgE production [10].

Biological context of Slc27a5

• Southern blot analysis indicated single-copy VLACSR genes in the mouse and human genomes [11].
• The BAL deletion lacked 670 base pairs of intervening sequence between secreted and membrane regions; the Kpn deletion lacked 830 base pairs in this region [12].
• The findings suggest that the kinetics and distribution of 111In-bleomycin in the normal BALB/c mouse can be influenced by pretreatment with BAL [13].
• Interestingly, virus-specific IgG2a and IgG2b antibody responses were affected locally in the BAL and in the serum of IgM(-/-) mice, while IgG1 responses remained largely normal [14].
• Also, increased reactive oxygen species (ROS) generation by TDI inhalation was diminished by administration of EGCG in BAL fluid [15].

Anatomical context of Slc27a5

• RESULTS: FATP5 is exclusively expressed by the liver and localized to the basal plasma membrane of hepatocytes, congruent with a role in LCFA uptake from the circulation [5].
• RESULTS: Although total bile acid concentrations were unchanged in bile, liver, urine, and feces of FATP5 knockout mice, the majority of gallbladder bile acids was unconjugated, and only a small percentage was conjugated [1].
• BAL 9, a lymphoma of the Lyt-1+,2+ T cell phenotype, was the most sensitive to DCF in vivo, and its DNA synthesis was inhibited more than 95% when cultured in the presence of dAr and DCF in vitro [3].
• The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade [16].
• Associated with this decrease in eosinophilic AI were significantly reduced levels of IL-5 in BAL fluid, of CD40 expression in peribronchial infiltrates, and of vascular cell adhesion molecule 1 expression in vascular endothelial cells, respectively [17].

Associations of Slc27a5 with chemical compounds

• Moreover, FATP5 deletion resulted in lower hepatic triglyceride and free fatty acid content despite increased expression of fatty acid synthetase and also caused a redistribution of lipids from liver to other LCFA-metabolizing tissues [5].
• BACKGROUND & AIMS: Fatty acid transport protein 5 (FATP5/Slc27a5) has been shown to be a multifunctional protein that in vitro increases both uptake of fluorescently labeled long-chain fatty acid (LCFA) analogues and bile acid/coenzyme A ligase activity on overexpression [5].
• In mice, unconjugated bile acids are conjugated with taurine by the liver-specific enzymes, bile acid-CoA ligase and bile acid-CoA:amino acid N-acyltransferase (BAT) [18].
• Mice lacking hepatic HNF4alpha expression exhibited markedly decreased expression of the very long chain acyl-CoA synthase-related gene (VLACSR), a mouse candidate for bile acid-CoA ligase, and BAT [18].
• Dimercaprol (BAL) administered 1 hr before 111In-bleomycin in the normal BALB/c mouse produced an early preferential hepatic loading of 111In-bleomycin without a loading of the spleen, skin, bone, or muscle [13].

Analytical, diagnostic and therapeutic context of Slc27a5

• Furthermore, numbers of IFN-gamma-producing CD4(+) effector T cells were reduced in the alveolar lavage (BAL) of micro MT mice but not IgM(-/-) mice [14].
• The three BALP isoforms were identified in extracts of human osteosarcoma (SaOS-2) cells, by HPLC, after separation by anion-exchange chromatography [19].
• All three BALP isoforms showed similar dose-dependent linearity in the commercial Alkphase-B and Tandem-MP Ostase immunoassays, r = 0.944 and r = 0.985, respectively (P < 0.001) [19].
• Analysis involved BAL, flow cytometry, adoptive transfer of OVA specific CD4 T cells, ex vivo cytokine expression and response to methacholine challenge [20].
• High-performance liquid chromatography (HPLC) separates three human bone alkaline phosphatase (BALP) isoforms in serum; two major BALP isoforms, B1 and B2, and a minor fraction, B/I, which is composed on average of 70% bone and 30% intestinal ALP [19].

References