{"gene":"SLC27A1","run_date":"2026-06-10T07:46:32","timeline":{"discoveries":[{"year":1999,"finding":"FATP1 (SLC27A1) possesses intrinsic very long chain acyl-CoA synthetase activity, preferentially activating C24:0 over C16:0. Active-site mutants M1 (6-aa substitution at residues 249-254) and M2 (59-aa deletion at residues 464-523) were both catalytically inactive, demonstrating two conserved domains are required for enzymatic function. The proposed mechanism for fatty acid uptake is esterification-coupled influx.","method":"Expression of FATP1-Myc/His in COS1 cells, acyl-CoA synthetase activity assays with C24:0 and C16:0 substrates, active-site mutagenesis, nickel-affinity partial purification","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic assay combined with active-site mutagenesis in a single rigorous study","pmids":["10593920"],"is_preprint":false},{"year":2000,"finding":"Murine FATP1 functionally complements the yeast fat1Δ deletion, restoring long-chain fatty acid transport (chain-length specific: myristate, palmitate, oleate, but not octanoate), very long chain acyl-CoA synthetase activity (lignoceryl-CoA), and β-oxidation of exogenous fatty acids. This establishes FATP1 and yeast Fat1p as functional orthologues with dual transport and acyl-CoA synthetase activities.","method":"Genetic complementation in S. cerevisiae fat1Δ strain; fluorescent fatty acid analogue accumulation assay; radiolabelled fatty acid transport and β-oxidation assays; acyl-CoA synthetase biochemical assay","journal":"European journal of biochemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis complementation with multiple orthogonal biochemical readouts, replicated across activities","pmids":["10880966"],"is_preprint":false},{"year":2000,"finding":"The human FATP1/SLC27A1 gene is organized in 12 exons spanning >13 kb, maps to chromosome 19p13.1 by FISH, and is most highly expressed in muscle and adipose tissue with barely detectable levels in liver.","method":"cDNA/genomic cloning, fluorescence in situ hybridization (FISH), Northern blot expression analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct structural characterization and chromosomal localization by FISH; single lab","pmids":["10873384"],"is_preprint":false},{"year":2002,"finding":"FATP1 stably expressed in 293 cells channels exogenous fatty acids preferentially into triacylglycerol (TG) biosynthesis, associated with increased diacylglycerol acyltransferase activity, while down-regulating de novo sphingomyelin and cholesterol synthesis. FATP1 expression increased both short-term FA uptake and long-term TG incorporation.","method":"Stable transfection of 293 cells; radiolabelled fatty acid incorporation assays ([14C]acetate, [3H]oleic acid, [14C]lignoceric acid); BODIPY fatty acid uptake; enzyme activity assays","journal":"Journal of lipid research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function cell model with multiple lipid metabolite readouts; single lab","pmids":["12235169"],"is_preprint":false},{"year":2005,"finding":"Among six murine FATP isoforms expressed in yeast, FATP1, -2, and -4 complemented defects in both fatty acid transport and very long chain fatty acid activation (C18:1, C20:4, C24:0). FATP3, -5, and -6 did not complement the transport deficiency despite plasma membrane localization, demonstrating isoform-specific division of transport versus acyl-CoA synthetase functions.","method":"Expression of each mmFATP isoform in defined yeast fat1Δ faa1Δ strain; fatty acid transport assays; acyl-CoA synthetase activity assays; subcellular localization","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic genetic complementation with six isoforms, multiple orthogonal functional assays","pmids":["15699031"],"is_preprint":false},{"year":2005,"finding":"In cultured human skeletal muscle cells, FATP1 localizes to intracellular membranes in a reticular/perinuclear pattern partly overlapping with Golgi (GM-130 marker), distinct from FAT/CD36 which is on the plasma membrane. Despite its intracellular localization, FATP1 overexpression stimulates palmitate and oleate transport and channels imported fatty acids away from complete oxidation toward triacylglyceride synthesis.","method":"Adenoviral gene delivery to primary human myotubes; EGFP fusion protein confocal microscopy; Golgi co-localization; radiolabelled fatty acid transport, oxidation, and esterification assays","journal":"American journal of physiology. Cell physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization with functional readout; single lab","pmids":["15897321"],"is_preprint":false},{"year":2006,"finding":"FATP1 is an insulin-sensitive fatty acid transporter: in adipocytes and skeletal muscle, FATP1 translocates from an intracellular compartment to the plasma membrane in response to insulin. FATP1-null mice show complete abolition of insulin-stimulated fatty acid uptake in adipocytes and greatly reduced uptake in skeletal muscle, while basal uptake is unaffected. Loss of FATP1 redistributes dietary lipids to the liver and fully protects against diet-induced obesity and insulin resistance.","method":"FATP1 knockout mouse model; insulin-stimulated fatty acid uptake assays in adipocytes and skeletal muscle; subcellular fractionation/translocation assays; metabolic phenotyping including serum LCFA, tissue lipid distribution, diet-induced obesity","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo knockout with multiple orthogonal mechanistic readouts and direct translocation assay; single rigorous study","pmids":["16611988"],"is_preprint":false},{"year":2009,"finding":"FATP1 localizes to mitochondria in L6E9 myotubes and skeletal muscle in vivo, and co-immunoprecipitates with CPT1 (carnitine palmitoyltransferase 1). Adenoviral overexpression of FATP1 increases fatty acid oxidation and palmitate esterification. Co-overexpression of FATP1 and CPT1 further enhanced mitochondrial fatty acid oxidation, and all effects were blocked by the CPT1 inhibitor etomoxir, establishing FATP1 as a collaborator with CPT1 for mitochondrial fatty acid import.","method":"Adenoviral overexpression in L6E9 myotubes; immunocytochemistry; co-immunoprecipitation from myotubes and rat skeletal muscle; fatty acid oxidation and esterification assays; etomoxir inhibitor experiments","journal":"Journal of lipid research","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP from native tissue plus cell-based functional assays with pharmacological inhibitor validation; single lab with multiple orthogonal methods","pmids":["19429947"],"is_preprint":false},{"year":2009,"finding":"FATP1 localizes to mitochondria in cultured myotubes (shown by subcellular fractionation immunoblot and FATP1-GFP immunocytology). FATP1 overexpression strongly stimulates CO2 production from glucose and activates the pyruvate dehydrogenase (PDH) complex and its PDH-E1 catalytic subunit, increasing E1β protein content without changing E2, E3BP, or E1α.","method":"Subcellular fractionation and immunoblot; FATP1-GFP immunocytology in myotubes; PDH complex activity and subunit protein quantification; CO2 production metabolic assay","journal":"Mitochondrion","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct mitochondrial localization and biochemical activity measurements; single lab","pmids":["19361580"],"is_preprint":false},{"year":2009,"finding":"In 3T3-L1 adipocytes, insulin-stimulated fatty acid influx mediated by FATP1 increases AMP/ATP ratio, which activates AMPK and its downstream target acetyl-CoA carboxylase. Knockdown of FATP1 by shRNA attenuates fatty acid-induced AMPK activation, demonstrating that FATP1-mediated acyl-CoA synthetase activity generates the AMP that signals to AMPK.","method":"shRNA knockdown of FATP1 in 3T3-L1 adipocytes; AMPK and ACC phosphorylation by immunoblot; intracellular AMP/ATP ratio measurement; palmitate/arachidonate uptake assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined biochemical signaling readout; single lab","pmids":["19560442"],"is_preprint":false},{"year":2010,"finding":"FATP1 mediates AMPK activation by adiponectin and insulin in adipocytes. Knockdown of FATP1 (and ACSL1) abolished the ~2-fold increase in AMP/ATP ratio and AMPK activation induced by adiponectin, and abrogated the 5-fold AMP/ATP increase and AMPK activation by insulin at 40 min. FATP1 and ACSL1 are also required for stimulation of long-chain fatty acid uptake by both hormones.","method":"siRNA knockdown of FATP1 and Acsl1 in mouse adipocytes; AMP/ATP ratio measurement; AMPK activation (phospho-AMPK immunoblot); long-chain fatty acid uptake assays","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with biochemical mechanistic readout; replicates and extends the AMPK finding; single lab","pmids":["20667975"],"is_preprint":false},{"year":2010,"finding":"FATP1 (SLC27A1) interacts with visual cycle proteins RPE65 (retinoid isomerase) and LRAT in the retinal pigment epithelium, identified by yeast two-hybrid screening with full-length human RPE65. The cytosolic C-terminal sequence of FATP1 mediates dose-dependent interaction with native RPE65 and LRAT. FATP1 markedly inhibits 11-cis retinol production by reducing all-trans retinyl ester production and RPE65 isomerase activity.","method":"Yeast two-hybrid screen; dose-dependent interaction assays with native RPE65 and LRAT; cellular reconstitution; 11-cis retinol production assay; colocalization in RPE","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus cellular reconstitution with functional readout; single lab","pmids":["20356843"],"is_preprint":false},{"year":2011,"finding":"Muscle-specific overexpression of FATP1 (Mck/Fatp1 transgenic mice) increases palmitate transport by 24% and oxidation by 35% in soleus muscle without altering triacylglycerol esterification or intrinsic mitochondrial oxidation rate. In vivo, FATP1 overexpression does not exacerbate diet-induced insulin resistance or intramuscular triacylglycerol accumulation, channeling LCFA toward oxidation rather than storage.","method":"Muscle-specific Fatp1 transgenic mice (Mck promoter); radiolabelled palmitate transport and oxidation assays in isolated soleus; in vivo LCFA uptake (BMIPP scintigraphy); glucose tolerance tests; intramuscular lipid quantification","journal":"Diabetologia","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo transgenic model with multiple orthogonal functional metabolic assays","pmids":["21442160"],"is_preprint":false},{"year":2012,"finding":"Overexpressed FATP1 localizes to the endoplasmic reticulum (not the plasma membrane) in 3T3-L1 adipocytes as shown by confocal microscopy and subcellular fractionation. Despite intracellular localization, FATP1 overexpression increases acyl-CoA synthetase activity and fatty acid uptake, suggesting that the mechanism of facilitated uptake is metabolic trapping rather than direct plasma membrane transport.","method":"Retroviral stable overexpression in 3T3-L1 adipocytes; confocal microscopy co-localization with ER markers; subcellular fractionation; acyl-CoA synthetase activity assay; fatty acid uptake assay; insulin stimulation","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct subcellular localization by two orthogonal methods with functional consequence; single lab","pmids":["23024797"],"is_preprint":false},{"year":2012,"finding":"Fatp1 deficiency in retina leads to decreased electroretinogram response to light and delayed recovery of the b-wave amplitude after bleaching, but without change in visual cycle speed. In 2-year-old Fatp1-/- mice, retinal aging is accelerated with choroid vascularization anomalies, Bruch membrane thickening, and photoreceptor outer segment disorganization.","method":"Fatp1-/- mouse model; electroretinography; b-wave bleaching/recovery kinetics; fatty acid pattern analysis; transmission electron microscopy of aged retina","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo knockout with electrophysiology and structural readouts; single lab","pmids":["23166839"],"is_preprint":false},{"year":2014,"finding":"FATP1 protein is most abundant in the mitochondrial fraction of mouse gastrocnemius muscle, specifically in outer membrane and soluble intermembrane space subfractions but not in the inner membrane plus matrix. FATP1 overexpression in mouse skeletal muscle reduces circulating fatty acid levels, lowers intramuscular triglyceride content, and enhances palmitate oxidation to CO2 while inhibiting β-hydroxybutyrate oxidation, suggesting FATP1 channels fatty acids to mitochondrial β-oxidation and spares ketone body utilization.","method":"Differential centrifugation subcellular fractionation; immunogold electron microscopy of FATP1-GFP in C2C12 myotubes; adenovirus-mediated in vivo overexpression in mouse gastrocnemius; serum metabolite measurements; isolated muscle strip oxidation assays","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — mitochondrial localization by two orthogonal methods (fractionation + immunogold EM) combined with in vivo functional metabolic assays","pmids":["24858472"],"is_preprint":false},{"year":2016,"finding":"FATP1 displays acyl-CoA synthetase activity for long-chain fatty acids in macrophages and controls macrophage substrate metabolism. Loss of FATP1 shifts macrophages toward enhanced glucose metabolism and exaggerates pro-inflammatory (classically activated) phenotype. Gain of FATP1 function in RAW 264.7 macrophages decreases glucose metabolism, diminishes pro-inflammatory activation, and modulates lipid mediator metabolism.","method":"Fatp1-/- bone marrow-derived macrophage isolation; FATP1-overexpressing RAW 264.7 cell line; bioenergetics assays (Seahorse); metabolomics; inflammatory marker quantification; bone marrow transplant chimeric mouse model with HFD challenge","journal":"Molecular metabolism","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal gain- and loss-of-function models with multiple orthogonal metabolic and inflammatory readouts in vitro and in vivo","pmids":["27408776"],"is_preprint":false},{"year":2017,"finding":"FATP1/SLC27A1 at the blood-brain barrier mediates DHA transport: FATP1-expressing HEK293 cells show significantly greater [14C]-DHA uptake than controls; FATP1 knockdown in hCMEC/D3 cells reduces DHA uptake by 59–73%. FATP1 also mediates efflux of DHA, taurine, and biotin. Insulin treatment for 30 min induces translocation of FATP1 to the plasma membrane of brain endothelial cells and enhances DHA uptake. Immunohistochemistry localizes FATP1 to the basal membrane of mouse brain microvessels.","method":"FATP1-expressing HEK293 cells; siRNA knockdown in hCMEC/D3 cells; [14C]-DHA uptake and efflux assays; insulin translocation assay; immunohistochemistry of mouse brain sections","journal":"Journal of neurochemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — gain- and loss-of-function with direct transport measurement, translocation experiment, and in vivo localization; single rigorous study with multiple orthogonal methods","pmids":["28035674"],"is_preprint":false},{"year":2018,"finding":"Melanomas significantly overexpress FATP1/SLC27A1, which mediates transfer of adipocyte-derived lipids to melanoma cells. FATP1 expression cooperates with BRAFV600E in transgenic zebrafish to accelerate melanoma development. Pharmacologic blockade with Lipofermata (FATP inhibitor) abrogates lipid transport and reduces melanoma growth and invasion.","method":"In vitro co-culture models; in vivo zebrafish transgenic melanoma model; mouse xenograft studies; Lipofermata pharmacologic inhibition; lipid transport assays","journal":"Cancer discovery","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple in vitro and in vivo models with genetic and pharmacologic interventions","pmids":["29903879"],"is_preprint":false},{"year":2019,"finding":"ER-β (estrogen receptor β) regulates FATP1/SLC27A1 expression in breast cancer cells. Estradiol and fatty acids stimulate FATP1 expression; treatment with ER-β antagonist PHTPP reduces FATP1 expression and inhibits fatty acid uptake and cell viability in four breast cancer cell lines. FATP1 inhibition with arylpiperazine 5k interferes with fatty acid uptake and cell viability.","method":"PHTPP (ER-β antagonist) and estradiol treatment; FATP1 expression by qPCR/Western; fatty acid uptake assays; cell viability assays in four breast cancer lines","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pharmacologic gain/loss-of-function across four cell lines with pathway placement; single lab","pmids":["31575907"],"is_preprint":false},{"year":2019,"finding":"PPARα and PPARγ activation by WY14643 and pioglitazone, respectively, attenuates oleate-induced total free fatty acid and triglyceride accumulation in macrophages by suppressing Fatp1 expression, reducing fatty acid influx. TNF-α similarly alleviates oleate-induced lipid accumulation through inhibition of Fatp1.","method":"Macrophage treatment with PPAR agonists and TNF-α; untargeted metabolomics; Fatp1 mRNA quantification; fatty acid and triglyceride measurements","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pharmacologic and cytokine intervention with metabolomics readout; PPAR-FATP1 pathway axis established; single lab","pmids":["30674874"],"is_preprint":false},{"year":2022,"finding":"Withaferin A (WA) induces white adipose tissue browning via a sympathetic nerve-adipose axis requiring the adipocytic Prdm16-FATP1 pathway. WA upregulates Prdm16 and FATP1 (Slc27a1) in inguinal WAT; sympathetic denervation blocks these effects. Prdm16 or FATP1 knockdown in iWAT abrogates WA-induced WAT browning and restores weight gain.","method":"Chemical sympathetic denervation; in vivo siRNA knockdown of Prdm16 and FATP1 in iWAT; energy expenditure measurement; Western blot and qPCR; adipose browning markers","journal":"Diabetes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo pathway placement by genetic knockdown with denervation control; single lab","pmids":["34732538"],"is_preprint":false},{"year":2024,"finding":"Iron (ferric ammonium citrate) reduces FATP1 protein abundance in brain microvascular endothelial cells (hCMEC/D3) by ~20% without affecting mRNA, and this is associated with a ~33% reduction in efflux of [14C]-DHA, demonstrating that FATP1 protein at the BBB mediates DHA efflux and is post-translationally regulated by iron.","method":"Ferric ammonium citrate treatment of hCMEC/D3 cells; RT-qPCR and Western blot; [14C]-DHA and [3H]-oleic acid uptake and efflux assays","journal":"Pharmaceutical research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein and functional measurements with mechanistic link; single lab","pmids":["39044044"],"is_preprint":false},{"year":2025,"finding":"SLC27A1 knockdown in colorectal cancer cell lines (Caco-2 and T84) significantly inhibits cell migration and invasion, and the transport of LCFAs via SLC27A1 enhances intracellular synthesis of diacylglycerol-3-phosphate (DAG-3P), a pathway linked to CRC metastasis.","method":"SLC27A1 knockdown in CRC cell lines; cell migration and invasion assays; DAG-3P pathway analysis","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single loss-of-function experiment, single lab, limited mechanistic detail in abstract","pmids":["40883416"],"is_preprint":false}],"current_model":"SLC27A1/FATP1 is an integral membrane very long-chain acyl-CoA synthetase that facilitates cellular uptake of long-chain fatty acids primarily through metabolic trapping (esterification-coupled influx); it localizes to both the plasma membrane (upon insulin-stimulated translocation) and intracellular membranes including the ER and the outer mitochondrial membrane, where it cooperates with CPT1 to promote fatty acid β-oxidation; in insulin-sensitive tissues its insulin-driven translocation to the plasma membrane is required for postprandial LCFA uptake, and its acyl-CoA synthetase activity generates AMP that activates AMPK; in the retina it interacts with RPE65 and LRAT to inhibit the visual cycle, and at the blood-brain barrier it mediates bidirectional DHA transport regulated by insulin translocation."},"narrative":{"mechanistic_narrative":"SLC27A1/FATP1 is an integral membrane very long-chain acyl-CoA synthetase that drives cellular uptake of long-chain fatty acids through esterification-coupled metabolic trapping [PMID:10593920, PMID:23024797]. Its enzymatic activity preferentially activates very long-chain substrates such as C24:0 and requires two conserved catalytic domains, and the same protein supports both fatty acid transport and acyl-CoA synthetase function as established by complementation of the yeast fat1Δ strain [PMID:10593920, PMID:10880966]. In insulin-responsive adipocytes and skeletal muscle, FATP1 translocates from an intracellular compartment to the plasma membrane upon insulin stimulation, and its loss abolishes insulin-stimulated fatty acid uptake, redistributes dietary lipid to the liver, and protects against diet-induced obesity and insulin resistance [PMID:16611988]. Imported fatty acids are channeled toward triacylglycerol synthesis or, via FATP1 at the outer mitochondrial membrane/intermembrane space where it cooperates with CPT1, toward β-oxidation [PMID:12235169, PMID:19429947, PMID:24858472]. The acyl-CoA synthetase reaction generates AMP that raises the AMP/ATP ratio and activates AMPK and acetyl-CoA carboxylase in response to insulin and adiponectin [PMID:19560442, PMID:20667975]. FATP1 also has tissue-specific roles: it transports DHA bidirectionally across the blood-brain barrier under insulin and iron regulation [PMID:28035674, PMID:39044044], interacts via its cytosolic C-terminus with the visual-cycle proteins RPE65 and LRAT to inhibit 11-cis retinol production [PMID:20356843], shapes macrophage substrate use and inflammatory phenotype [PMID:27408776], and is exploited by melanoma and other cancers to acquire fatty acids and promote growth and invasion [PMID:29903879, PMID:31575907].","teleology":[{"year":1999,"claim":"Established that FATP1 is itself an enzyme — a very long-chain acyl-CoA synthetase — rather than a passive carrier, defining esterification-coupled influx as the proposed uptake mechanism.","evidence":"Acyl-CoA synthetase assays with C24:0/C16:0 and active-site mutagenesis of FATP1-Myc/His expressed in COS1 cells","pmids":["10593920"],"confidence":"High","gaps":["Did not resolve whether transport occurs by direct membrane translocation or solely metabolic trapping","No structural model of the catalytic domains"]},{"year":2000,"claim":"Demonstrated that a single FATP1 protein carries both fatty acid transport and acyl-CoA synthetase/β-oxidation functions, conserved with yeast Fat1p, with chain-length selectivity.","evidence":"Genetic complementation of S. cerevisiae fat1Δ with murine FATP1 plus transport, synthetase, and β-oxidation assays","pmids":["10880966"],"confidence":"High","gaps":["Did not separate transport from synthetase activity mechanistically","Mammalian tissue context untested"]},{"year":2000,"claim":"Defined the human SLC27A1 gene structure, chromosomal locus, and tissue expression bias toward muscle and adipose, framing where FATP1 acts.","evidence":"cDNA/genomic cloning, FISH mapping to 19p13.1, and Northern blot expression","pmids":["10873384"],"confidence":"Medium","gaps":["Expression survey is descriptive, not functional","No protein-level tissue quantification"]},{"year":2005,"claim":"Showed that FATP isoforms divide transport versus synthetase roles, and that FATP1 can stimulate fatty acid uptake and divert it to TG synthesis even from intracellular membranes, challenging a strict plasma-membrane transporter model.","evidence":"Six-isoform yeast complementation; adenoviral EGFP-FATP1 in human myotubes with localization and transport/oxidation/esterification assays","pmids":["15699031","15897321"],"confidence":"High","gaps":["Localization in primary myotubes may differ from native tissue","Mechanism reconciling intracellular localization with surface uptake unresolved"]},{"year":2006,"claim":"Established FATP1 as the insulin-sensitive fatty acid transporter in vivo: insulin drives its translocation to the plasma membrane, and its loss abolishes insulin-stimulated uptake and protects against metabolic disease.","evidence":"FATP1-null mice with insulin-stimulated uptake, translocation fractionation, and diet-induced obesity phenotyping","pmids":["16611988"],"confidence":"High","gaps":["Molecular machinery of insulin-driven translocation not identified","Compensation by other FATP/ACSL isoforms in muscle not fully resolved"]},{"year":2009,"claim":"Placed FATP1 at the mitochondrion as a partner of CPT1, linking fatty acid import to β-oxidation, and showed FATP1 can also stimulate glucose oxidation via PDH.","evidence":"Co-IP of FATP1 with CPT1 from myotubes and rat muscle, etomoxir-sensitive oxidation assays, and subcellular fractionation/PDH activity measurements","pmids":["19429947","19361580"],"confidence":"High","gaps":["Reciprocal Co-IP and stoichiometry of the FATP1–CPT1 interaction not defined","Mechanism by which FATP1 activates PDH-E1β unknown"]},{"year":2010,"claim":"Identified FATP1 acyl-CoA synthetase activity as the source of AMP that activates AMPK signaling downstream of insulin and adiponectin.","evidence":"shRNA/siRNA knockdown of FATP1 (with ACSL1) in adipocytes, AMP/ATP ratio measurement, and phospho-AMPK/ACC immunoblots","pmids":["19560442","20667975"],"confidence":"Medium","gaps":["Relative contribution of FATP1 versus ACSL1 to the AMP pool not separated","Single lab"]},{"year":2010,"claim":"Revealed a non-metabolic moonlighting role: FATP1 binds RPE65 and LRAT via its cytosolic C-terminus to inhibit the retinal visual cycle.","evidence":"Yeast two-hybrid with RPE65, dose-dependent interaction with native RPE65/LRAT, and 11-cis retinol production assays in RPE","pmids":["20356843"],"confidence":"Medium","gaps":["Physiological significance in vivo not established by this study","Whether inhibition depends on FATP1 enzymatic activity unknown"]},{"year":2011,"claim":"Confirmed in vivo that FATP1 can channel muscle fatty acids toward oxidation rather than storage without worsening insulin resistance, distinguishing FATP1 from lipotoxic transporters.","evidence":"Muscle-specific Mck/Fatp1 transgenic mice with palmitate transport/oxidation, in vivo BMIPP uptake, and glucose tolerance tests","pmids":["21442160"],"confidence":"High","gaps":["Does not address adipose-specific functions","Mechanism directing flux to oxidation vs esterification not defined"]},{"year":2012,"claim":"Resolved that FATP1 facilitates uptake by metabolic trapping from the ER rather than direct plasma-membrane transport, and refined its retinal phenotype.","evidence":"Retroviral FATP1 overexpression in 3T3-L1 with ER co-localization/fractionation and uptake assays; Fatp1-/- retinal ERG and EM","pmids":["23024797","23166839"],"confidence":"Medium","gaps":["Apparent conflict with insulin-driven plasma-membrane translocation not fully reconciled","Retinal aging mechanism (vascular vs metabolic) unresolved"]},{"year":2014,"claim":"Localized FATP1 specifically to the mitochondrial outer membrane and intermembrane space and showed it channels muscle fatty acids to β-oxidation while sparing ketone bodies.","evidence":"Differential fractionation plus immunogold EM of FATP1-GFP, with in vivo adenoviral overexpression and isolated muscle oxidation assays","pmids":["24858472"],"confidence":"High","gaps":["Mechanism of FATP1 targeting to the outer mitochondrial membrane unknown","How soluble IMS pool functions unclear"]},{"year":2016,"claim":"Extended FATP1 function to immune cells, showing its acyl-CoA synthetase activity sets macrophage substrate preference and restrains pro-inflammatory activation.","evidence":"Reciprocal Fatp1-/- BMDM and FATP1-overexpressing RAW264.7 with Seahorse bioenergetics, metabolomics, and HFD bone-marrow chimeras","pmids":["27408776"],"confidence":"High","gaps":["Lipid mediators responsible for the inflammatory phenotype not pinpointed","Link to the glucose/PDH axis not directly tested"]},{"year":2017,"claim":"Demonstrated FATP1 mediates insulin-regulated bidirectional DHA transport at the blood-brain barrier, extending its insulin-translocation behavior to endothelium.","evidence":"FATP1 overexpression/knockdown in HEK293 and hCMEC/D3 with [14C]-DHA uptake/efflux, insulin translocation, and mouse microvessel immunohistochemistry","pmids":["28035674"],"confidence":"High","gaps":["Mechanism of efflux versus influx directionality not defined","Whether DHA transport requires synthetase activity untested"]},{"year":2018,"claim":"Implicated FATP1 in cancer by showing it imports adipocyte-derived lipids to fuel melanoma growth and is druggable with Lipofermata.","evidence":"Co-culture lipid transfer, BRAFV600E zebrafish melanoma model, mouse xenografts, and Lipofermata inhibition","pmids":["29903879"],"confidence":"High","gaps":["Downstream lipid signaling driving invasion not detailed","Selectivity of pharmacologic inhibition for FATP1 not fully addressed"]},{"year":2019,"claim":"Defined upstream transcriptional control of FATP1 by nuclear receptors — ER-β driving and PPARα/γ plus TNF-α suppressing expression — tying its fatty acid uptake to hormonal and inflammatory cues.","evidence":"ER-β antagonist/estradiol in breast cancer lines and PPAR agonist/TNF-α metabolomics in macrophages, with FATP1 expression and uptake readouts","pmids":["31575907","30674874"],"confidence":"Medium","gaps":["Direct transcriptional binding to the SLC27A1 promoter not shown","Single-lab pharmacologic interventions"]},{"year":2022,"claim":"Positioned FATP1 within an adipose browning program downstream of sympathetic Prdm16 signaling.","evidence":"In vivo iWAT siRNA knockdown of Prdm16/FATP1 with sympathetic denervation and energy expenditure measures in Withaferin A-treated mice","pmids":["34732538"],"confidence":"Medium","gaps":["Mechanistic link between FATP1 fatty acid handling and browning not defined","Single lab"]},{"year":2024,"claim":"Showed FATP1 protein at the BBB is post-translationally downregulated by iron, reducing DHA efflux.","evidence":"Ferric ammonium citrate treatment of hCMEC/D3 with RT-qPCR, Western blot, and [14C]-DHA efflux assays","pmids":["39044044"],"confidence":"Medium","gaps":["Mechanism of iron-dependent protein turnover unknown","Physiological relevance in vivo untested"]},{"year":2025,"claim":"Linked FATP1-mediated LCFA transport to colorectal cancer migration/invasion via DAG-3P synthesis.","evidence":"SLC27A1 knockdown in Caco-2 and T84 cells with migration/invasion and DAG-3P pathway analysis","pmids":["40883416"],"confidence":"Low","gaps":["Single loss-of-function experiment without rescue or in vivo validation","Mechanistic detail limited"]},{"year":null,"claim":"The molecular machinery that reconciles FATP1's intracellular (ER/mitochondrial) localization with its insulin-stimulated plasma-membrane translocation, and the structural basis of its dual transport/synthetase activity, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of FATP1","Translocation trafficking partners unidentified","Whether moonlighting (RPE65/LRAT) and cancer roles require catalytic activity unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[0,1,4,13,16]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[6,17]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[3,5,17]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[6,17]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[5,13]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[7,8,15]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0,3,6,7,15]},{"term_id":"R-HSA-382551","term_label":"Transport of small molecules","supporting_discovery_ids":[6,17]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[9,10]}],"complexes":[],"partners":["CPT1","RPE65","LRAT","ACSL1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6PCB7","full_name":"Long-chain fatty acid transport protein 1","aliases":["Arachidonate--CoA ligase","Fatty acid transport protein 1","FATP-1","Long-chain-fatty-acid--CoA ligase","Solute carrier family 27 member 1","Very long-chain acyl-CoA synthetase"],"length_aa":646,"mass_kda":71.1,"function":"Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport at the plasma membrane (PubMed:12556534, PubMed:20530735, PubMed:21395585, PubMed:28178239). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake. May act directly as a bona fide transporter, or alternatively, in a cytoplasmic or membrane-associated multimeric protein complex to trap and draw fatty acids towards accumulation. Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis. May be involved in regulation of cholesterol metabolism (By similarity). 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crystallization of intact F-ATP synthase isolated from bovine heart mitochondria.","date":"2013","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/24316832","citation_count":6,"is_preprint":false},{"pmid":"30791207","id":"PMC_30791207","title":"The structural features of Acetobacterium woodii F-ATP synthase reveal the importance of the unique subunit γ-loop in Na+ translocation and ATP synthesis.","date":"2019","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/30791207","citation_count":6,"is_preprint":false},{"pmid":"26613566","id":"PMC_26613566","title":"Stoichiometry and deletion analyses of subunits in the heterotrimeric F-ATP synthase c ring from the acetogenic bacterium Acetobacterium woodii.","date":"2015","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/26613566","citation_count":6,"is_preprint":false},{"pmid":"21328100","id":"PMC_21328100","title":"Association between polymorphisms in the SLC27A1 gene and milk production traits in Chinese Holstein 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Active-site mutants M1 (6-aa substitution at residues 249-254) and M2 (59-aa deletion at residues 464-523) were both catalytically inactive, demonstrating two conserved domains are required for enzymatic function. The proposed mechanism for fatty acid uptake is esterification-coupled influx.\",\n      \"method\": \"Expression of FATP1-Myc/His in COS1 cells, acyl-CoA synthetase activity assays with C24:0 and C16:0 substrates, active-site mutagenesis, nickel-affinity partial purification\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic assay combined with active-site mutagenesis in a single rigorous study\",\n      \"pmids\": [\"10593920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Murine FATP1 functionally complements the yeast fat1Δ deletion, restoring long-chain fatty acid transport (chain-length specific: myristate, palmitate, oleate, but not octanoate), very long chain acyl-CoA synthetase activity (lignoceryl-CoA), and β-oxidation of exogenous fatty acids. This establishes FATP1 and yeast Fat1p as functional orthologues with dual transport and acyl-CoA synthetase activities.\",\n      \"method\": \"Genetic complementation in S. cerevisiae fat1Δ strain; fluorescent fatty acid analogue accumulation assay; radiolabelled fatty acid transport and β-oxidation assays; acyl-CoA synthetase biochemical assay\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis complementation with multiple orthogonal biochemical readouts, replicated across activities\",\n      \"pmids\": [\"10880966\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The human FATP1/SLC27A1 gene is organized in 12 exons spanning >13 kb, maps to chromosome 19p13.1 by FISH, and is most highly expressed in muscle and adipose tissue with barely detectable levels in liver.\",\n      \"method\": \"cDNA/genomic cloning, fluorescence in situ hybridization (FISH), Northern blot expression analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct structural characterization and chromosomal localization by FISH; single lab\",\n      \"pmids\": [\"10873384\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"FATP1 stably expressed in 293 cells channels exogenous fatty acids preferentially into triacylglycerol (TG) biosynthesis, associated with increased diacylglycerol acyltransferase activity, while down-regulating de novo sphingomyelin and cholesterol synthesis. FATP1 expression increased both short-term FA uptake and long-term TG incorporation.\",\n      \"method\": \"Stable transfection of 293 cells; radiolabelled fatty acid incorporation assays ([14C]acetate, [3H]oleic acid, [14C]lignoceric acid); BODIPY fatty acid uptake; enzyme activity assays\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function cell model with multiple lipid metabolite readouts; single lab\",\n      \"pmids\": [\"12235169\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Among six murine FATP isoforms expressed in yeast, FATP1, -2, and -4 complemented defects in both fatty acid transport and very long chain fatty acid activation (C18:1, C20:4, C24:0). FATP3, -5, and -6 did not complement the transport deficiency despite plasma membrane localization, demonstrating isoform-specific division of transport versus acyl-CoA synthetase functions.\",\n      \"method\": \"Expression of each mmFATP isoform in defined yeast fat1Δ faa1Δ strain; fatty acid transport assays; acyl-CoA synthetase activity assays; subcellular localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic genetic complementation with six isoforms, multiple orthogonal functional assays\",\n      \"pmids\": [\"15699031\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"In cultured human skeletal muscle cells, FATP1 localizes to intracellular membranes in a reticular/perinuclear pattern partly overlapping with Golgi (GM-130 marker), distinct from FAT/CD36 which is on the plasma membrane. Despite its intracellular localization, FATP1 overexpression stimulates palmitate and oleate transport and channels imported fatty acids away from complete oxidation toward triacylglyceride synthesis.\",\n      \"method\": \"Adenoviral gene delivery to primary human myotubes; EGFP fusion protein confocal microscopy; Golgi co-localization; radiolabelled fatty acid transport, oxidation, and esterification assays\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization with functional readout; single lab\",\n      \"pmids\": [\"15897321\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"FATP1 is an insulin-sensitive fatty acid transporter: in adipocytes and skeletal muscle, FATP1 translocates from an intracellular compartment to the plasma membrane in response to insulin. FATP1-null mice show complete abolition of insulin-stimulated fatty acid uptake in adipocytes and greatly reduced uptake in skeletal muscle, while basal uptake is unaffected. Loss of FATP1 redistributes dietary lipids to the liver and fully protects against diet-induced obesity and insulin resistance.\",\n      \"method\": \"FATP1 knockout mouse model; insulin-stimulated fatty acid uptake assays in adipocytes and skeletal muscle; subcellular fractionation/translocation assays; metabolic phenotyping including serum LCFA, tissue lipid distribution, diet-induced obesity\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo knockout with multiple orthogonal mechanistic readouts and direct translocation assay; single rigorous study\",\n      \"pmids\": [\"16611988\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"FATP1 localizes to mitochondria in L6E9 myotubes and skeletal muscle in vivo, and co-immunoprecipitates with CPT1 (carnitine palmitoyltransferase 1). Adenoviral overexpression of FATP1 increases fatty acid oxidation and palmitate esterification. Co-overexpression of FATP1 and CPT1 further enhanced mitochondrial fatty acid oxidation, and all effects were blocked by the CPT1 inhibitor etomoxir, establishing FATP1 as a collaborator with CPT1 for mitochondrial fatty acid import.\",\n      \"method\": \"Adenoviral overexpression in L6E9 myotubes; immunocytochemistry; co-immunoprecipitation from myotubes and rat skeletal muscle; fatty acid oxidation and esterification assays; etomoxir inhibitor experiments\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP from native tissue plus cell-based functional assays with pharmacological inhibitor validation; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"19429947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"FATP1 localizes to mitochondria in cultured myotubes (shown by subcellular fractionation immunoblot and FATP1-GFP immunocytology). FATP1 overexpression strongly stimulates CO2 production from glucose and activates the pyruvate dehydrogenase (PDH) complex and its PDH-E1 catalytic subunit, increasing E1β protein content without changing E2, E3BP, or E1α.\",\n      \"method\": \"Subcellular fractionation and immunoblot; FATP1-GFP immunocytology in myotubes; PDH complex activity and subunit protein quantification; CO2 production metabolic assay\",\n      \"journal\": \"Mitochondrion\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct mitochondrial localization and biochemical activity measurements; single lab\",\n      \"pmids\": [\"19361580\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"In 3T3-L1 adipocytes, insulin-stimulated fatty acid influx mediated by FATP1 increases AMP/ATP ratio, which activates AMPK and its downstream target acetyl-CoA carboxylase. Knockdown of FATP1 by shRNA attenuates fatty acid-induced AMPK activation, demonstrating that FATP1-mediated acyl-CoA synthetase activity generates the AMP that signals to AMPK.\",\n      \"method\": \"shRNA knockdown of FATP1 in 3T3-L1 adipocytes; AMPK and ACC phosphorylation by immunoblot; intracellular AMP/ATP ratio measurement; palmitate/arachidonate uptake assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined biochemical signaling readout; single lab\",\n      \"pmids\": [\"19560442\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"FATP1 mediates AMPK activation by adiponectin and insulin in adipocytes. Knockdown of FATP1 (and ACSL1) abolished the ~2-fold increase in AMP/ATP ratio and AMPK activation induced by adiponectin, and abrogated the 5-fold AMP/ATP increase and AMPK activation by insulin at 40 min. FATP1 and ACSL1 are also required for stimulation of long-chain fatty acid uptake by both hormones.\",\n      \"method\": \"siRNA knockdown of FATP1 and Acsl1 in mouse adipocytes; AMP/ATP ratio measurement; AMPK activation (phospho-AMPK immunoblot); long-chain fatty acid uptake assays\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with biochemical mechanistic readout; replicates and extends the AMPK finding; single lab\",\n      \"pmids\": [\"20667975\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"FATP1 (SLC27A1) interacts with visual cycle proteins RPE65 (retinoid isomerase) and LRAT in the retinal pigment epithelium, identified by yeast two-hybrid screening with full-length human RPE65. The cytosolic C-terminal sequence of FATP1 mediates dose-dependent interaction with native RPE65 and LRAT. FATP1 markedly inhibits 11-cis retinol production by reducing all-trans retinyl ester production and RPE65 isomerase activity.\",\n      \"method\": \"Yeast two-hybrid screen; dose-dependent interaction assays with native RPE65 and LRAT; cellular reconstitution; 11-cis retinol production assay; colocalization in RPE\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus cellular reconstitution with functional readout; single lab\",\n      \"pmids\": [\"20356843\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Muscle-specific overexpression of FATP1 (Mck/Fatp1 transgenic mice) increases palmitate transport by 24% and oxidation by 35% in soleus muscle without altering triacylglycerol esterification or intrinsic mitochondrial oxidation rate. In vivo, FATP1 overexpression does not exacerbate diet-induced insulin resistance or intramuscular triacylglycerol accumulation, channeling LCFA toward oxidation rather than storage.\",\n      \"method\": \"Muscle-specific Fatp1 transgenic mice (Mck promoter); radiolabelled palmitate transport and oxidation assays in isolated soleus; in vivo LCFA uptake (BMIPP scintigraphy); glucose tolerance tests; intramuscular lipid quantification\",\n      \"journal\": \"Diabetologia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo transgenic model with multiple orthogonal functional metabolic assays\",\n      \"pmids\": [\"21442160\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Overexpressed FATP1 localizes to the endoplasmic reticulum (not the plasma membrane) in 3T3-L1 adipocytes as shown by confocal microscopy and subcellular fractionation. Despite intracellular localization, FATP1 overexpression increases acyl-CoA synthetase activity and fatty acid uptake, suggesting that the mechanism of facilitated uptake is metabolic trapping rather than direct plasma membrane transport.\",\n      \"method\": \"Retroviral stable overexpression in 3T3-L1 adipocytes; confocal microscopy co-localization with ER markers; subcellular fractionation; acyl-CoA synthetase activity assay; fatty acid uptake assay; insulin stimulation\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct subcellular localization by two orthogonal methods with functional consequence; single lab\",\n      \"pmids\": [\"23024797\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Fatp1 deficiency in retina leads to decreased electroretinogram response to light and delayed recovery of the b-wave amplitude after bleaching, but without change in visual cycle speed. In 2-year-old Fatp1-/- mice, retinal aging is accelerated with choroid vascularization anomalies, Bruch membrane thickening, and photoreceptor outer segment disorganization.\",\n      \"method\": \"Fatp1-/- mouse model; electroretinography; b-wave bleaching/recovery kinetics; fatty acid pattern analysis; transmission electron microscopy of aged retina\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo knockout with electrophysiology and structural readouts; single lab\",\n      \"pmids\": [\"23166839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"FATP1 protein is most abundant in the mitochondrial fraction of mouse gastrocnemius muscle, specifically in outer membrane and soluble intermembrane space subfractions but not in the inner membrane plus matrix. FATP1 overexpression in mouse skeletal muscle reduces circulating fatty acid levels, lowers intramuscular triglyceride content, and enhances palmitate oxidation to CO2 while inhibiting β-hydroxybutyrate oxidation, suggesting FATP1 channels fatty acids to mitochondrial β-oxidation and spares ketone body utilization.\",\n      \"method\": \"Differential centrifugation subcellular fractionation; immunogold electron microscopy of FATP1-GFP in C2C12 myotubes; adenovirus-mediated in vivo overexpression in mouse gastrocnemius; serum metabolite measurements; isolated muscle strip oxidation assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mitochondrial localization by two orthogonal methods (fractionation + immunogold EM) combined with in vivo functional metabolic assays\",\n      \"pmids\": [\"24858472\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"FATP1 displays acyl-CoA synthetase activity for long-chain fatty acids in macrophages and controls macrophage substrate metabolism. Loss of FATP1 shifts macrophages toward enhanced glucose metabolism and exaggerates pro-inflammatory (classically activated) phenotype. Gain of FATP1 function in RAW 264.7 macrophages decreases glucose metabolism, diminishes pro-inflammatory activation, and modulates lipid mediator metabolism.\",\n      \"method\": \"Fatp1-/- bone marrow-derived macrophage isolation; FATP1-overexpressing RAW 264.7 cell line; bioenergetics assays (Seahorse); metabolomics; inflammatory marker quantification; bone marrow transplant chimeric mouse model with HFD challenge\",\n      \"journal\": \"Molecular metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal gain- and loss-of-function models with multiple orthogonal metabolic and inflammatory readouts in vitro and in vivo\",\n      \"pmids\": [\"27408776\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"FATP1/SLC27A1 at the blood-brain barrier mediates DHA transport: FATP1-expressing HEK293 cells show significantly greater [14C]-DHA uptake than controls; FATP1 knockdown in hCMEC/D3 cells reduces DHA uptake by 59–73%. FATP1 also mediates efflux of DHA, taurine, and biotin. Insulin treatment for 30 min induces translocation of FATP1 to the plasma membrane of brain endothelial cells and enhances DHA uptake. Immunohistochemistry localizes FATP1 to the basal membrane of mouse brain microvessels.\",\n      \"method\": \"FATP1-expressing HEK293 cells; siRNA knockdown in hCMEC/D3 cells; [14C]-DHA uptake and efflux assays; insulin translocation assay; immunohistochemistry of mouse brain sections\",\n      \"journal\": \"Journal of neurochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — gain- and loss-of-function with direct transport measurement, translocation experiment, and in vivo localization; single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"28035674\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Melanomas significantly overexpress FATP1/SLC27A1, which mediates transfer of adipocyte-derived lipids to melanoma cells. FATP1 expression cooperates with BRAFV600E in transgenic zebrafish to accelerate melanoma development. Pharmacologic blockade with Lipofermata (FATP inhibitor) abrogates lipid transport and reduces melanoma growth and invasion.\",\n      \"method\": \"In vitro co-culture models; in vivo zebrafish transgenic melanoma model; mouse xenograft studies; Lipofermata pharmacologic inhibition; lipid transport assays\",\n      \"journal\": \"Cancer discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple in vitro and in vivo models with genetic and pharmacologic interventions\",\n      \"pmids\": [\"29903879\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ER-β (estrogen receptor β) regulates FATP1/SLC27A1 expression in breast cancer cells. Estradiol and fatty acids stimulate FATP1 expression; treatment with ER-β antagonist PHTPP reduces FATP1 expression and inhibits fatty acid uptake and cell viability in four breast cancer cell lines. FATP1 inhibition with arylpiperazine 5k interferes with fatty acid uptake and cell viability.\",\n      \"method\": \"PHTPP (ER-β antagonist) and estradiol treatment; FATP1 expression by qPCR/Western; fatty acid uptake assays; cell viability assays in four breast cancer lines\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pharmacologic gain/loss-of-function across four cell lines with pathway placement; single lab\",\n      \"pmids\": [\"31575907\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PPARα and PPARγ activation by WY14643 and pioglitazone, respectively, attenuates oleate-induced total free fatty acid and triglyceride accumulation in macrophages by suppressing Fatp1 expression, reducing fatty acid influx. TNF-α similarly alleviates oleate-induced lipid accumulation through inhibition of Fatp1.\",\n      \"method\": \"Macrophage treatment with PPAR agonists and TNF-α; untargeted metabolomics; Fatp1 mRNA quantification; fatty acid and triglyceride measurements\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pharmacologic and cytokine intervention with metabolomics readout; PPAR-FATP1 pathway axis established; single lab\",\n      \"pmids\": [\"30674874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Withaferin A (WA) induces white adipose tissue browning via a sympathetic nerve-adipose axis requiring the adipocytic Prdm16-FATP1 pathway. WA upregulates Prdm16 and FATP1 (Slc27a1) in inguinal WAT; sympathetic denervation blocks these effects. Prdm16 or FATP1 knockdown in iWAT abrogates WA-induced WAT browning and restores weight gain.\",\n      \"method\": \"Chemical sympathetic denervation; in vivo siRNA knockdown of Prdm16 and FATP1 in iWAT; energy expenditure measurement; Western blot and qPCR; adipose browning markers\",\n      \"journal\": \"Diabetes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo pathway placement by genetic knockdown with denervation control; single lab\",\n      \"pmids\": [\"34732538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Iron (ferric ammonium citrate) reduces FATP1 protein abundance in brain microvascular endothelial cells (hCMEC/D3) by ~20% without affecting mRNA, and this is associated with a ~33% reduction in efflux of [14C]-DHA, demonstrating that FATP1 protein at the BBB mediates DHA efflux and is post-translationally regulated by iron.\",\n      \"method\": \"Ferric ammonium citrate treatment of hCMEC/D3 cells; RT-qPCR and Western blot; [14C]-DHA and [3H]-oleic acid uptake and efflux assays\",\n      \"journal\": \"Pharmaceutical research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein and functional measurements with mechanistic link; single lab\",\n      \"pmids\": [\"39044044\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SLC27A1 knockdown in colorectal cancer cell lines (Caco-2 and T84) significantly inhibits cell migration and invasion, and the transport of LCFAs via SLC27A1 enhances intracellular synthesis of diacylglycerol-3-phosphate (DAG-3P), a pathway linked to CRC metastasis.\",\n      \"method\": \"SLC27A1 knockdown in CRC cell lines; cell migration and invasion assays; DAG-3P pathway analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single loss-of-function experiment, single lab, limited mechanistic detail in abstract\",\n      \"pmids\": [\"40883416\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLC27A1/FATP1 is an integral membrane very long-chain acyl-CoA synthetase that facilitates cellular uptake of long-chain fatty acids primarily through metabolic trapping (esterification-coupled influx); it localizes to both the plasma membrane (upon insulin-stimulated translocation) and intracellular membranes including the ER and the outer mitochondrial membrane, where it cooperates with CPT1 to promote fatty acid β-oxidation; in insulin-sensitive tissues its insulin-driven translocation to the plasma membrane is required for postprandial LCFA uptake, and its acyl-CoA synthetase activity generates AMP that activates AMPK; in the retina it interacts with RPE65 and LRAT to inhibit the visual cycle, and at the blood-brain barrier it mediates bidirectional DHA transport regulated by insulin translocation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SLC27A1/FATP1 is an integral membrane very long-chain acyl-CoA synthetase that drives cellular uptake of long-chain fatty acids through esterification-coupled metabolic trapping [#0, #13]. Its enzymatic activity preferentially activates very long-chain substrates such as C24:0 and requires two conserved catalytic domains, and the same protein supports both fatty acid transport and acyl-CoA synthetase function as established by complementation of the yeast fat1\\u0394 strain [#0, #1]. In insulin-responsive adipocytes and skeletal muscle, FATP1 translocates from an intracellular compartment to the plasma membrane upon insulin stimulation, and its loss abolishes insulin-stimulated fatty acid uptake, redistributes dietary lipid to the liver, and protects against diet-induced obesity and insulin resistance [#6]. Imported fatty acids are channeled toward triacylglycerol synthesis or, via FATP1 at the outer mitochondrial membrane/intermembrane space where it cooperates with CPT1, toward \\u03b2-oxidation [#3, #7, #15]. The acyl-CoA synthetase reaction generates AMP that raises the AMP/ATP ratio and activates AMPK and acetyl-CoA carboxylase in response to insulin and adiponectin [#9, #10]. FATP1 also has tissue-specific roles: it transports DHA bidirectionally across the blood-brain barrier under insulin and iron regulation [#17, #22], interacts via its cytosolic C-terminus with the visual-cycle proteins RPE65 and LRAT to inhibit 11-cis retinol production [#11], shapes macrophage substrate use and inflammatory phenotype [#16], and is exploited by melanoma and other cancers to acquire fatty acids and promote growth and invasion [#18, #19].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established that FATP1 is itself an enzyme \\u2014 a very long-chain acyl-CoA synthetase \\u2014 rather than a passive carrier, defining esterification-coupled influx as the proposed uptake mechanism.\",\n      \"evidence\": \"Acyl-CoA synthetase assays with C24:0/C16:0 and active-site mutagenesis of FATP1-Myc/His expressed in COS1 cells\",\n      \"pmids\": [\"10593920\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve whether transport occurs by direct membrane translocation or solely metabolic trapping\", \"No structural model of the catalytic domains\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Demonstrated that a single FATP1 protein carries both fatty acid transport and acyl-CoA synthetase/\\u03b2-oxidation functions, conserved with yeast Fat1p, with chain-length selectivity.\",\n      \"evidence\": \"Genetic complementation of S. cerevisiae fat1\\u0394 with murine FATP1 plus transport, synthetase, and \\u03b2-oxidation assays\",\n      \"pmids\": [\"10880966\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not separate transport from synthetase activity mechanistically\", \"Mammalian tissue context untested\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Defined the human SLC27A1 gene structure, chromosomal locus, and tissue expression bias toward muscle and adipose, framing where FATP1 acts.\",\n      \"evidence\": \"cDNA/genomic cloning, FISH mapping to 19p13.1, and Northern blot expression\",\n      \"pmids\": [\"10873384\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Expression survey is descriptive, not functional\", \"No protein-level tissue quantification\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Showed that FATP isoforms divide transport versus synthetase roles, and that FATP1 can stimulate fatty acid uptake and divert it to TG synthesis even from intracellular membranes, challenging a strict plasma-membrane transporter model.\",\n      \"evidence\": \"Six-isoform yeast complementation; adenoviral EGFP-FATP1 in human myotubes with localization and transport/oxidation/esterification assays\",\n      \"pmids\": [\"15699031\", \"15897321\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Localization in primary myotubes may differ from native tissue\", \"Mechanism reconciling intracellular localization with surface uptake unresolved\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Established FATP1 as the insulin-sensitive fatty acid transporter in vivo: insulin drives its translocation to the plasma membrane, and its loss abolishes insulin-stimulated uptake and protects against metabolic disease.\",\n      \"evidence\": \"FATP1-null mice with insulin-stimulated uptake, translocation fractionation, and diet-induced obesity phenotyping\",\n      \"pmids\": [\"16611988\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular machinery of insulin-driven translocation not identified\", \"Compensation by other FATP/ACSL isoforms in muscle not fully resolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Placed FATP1 at the mitochondrion as a partner of CPT1, linking fatty acid import to \\u03b2-oxidation, and showed FATP1 can also stimulate glucose oxidation via PDH.\",\n      \"evidence\": \"Co-IP of FATP1 with CPT1 from myotubes and rat muscle, etomoxir-sensitive oxidation assays, and subcellular fractionation/PDH activity measurements\",\n      \"pmids\": [\"19429947\", \"19361580\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Reciprocal Co-IP and stoichiometry of the FATP1\\u2013CPT1 interaction not defined\", \"Mechanism by which FATP1 activates PDH-E1\\u03b2 unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified FATP1 acyl-CoA synthetase activity as the source of AMP that activates AMPK signaling downstream of insulin and adiponectin.\",\n      \"evidence\": \"shRNA/siRNA knockdown of FATP1 (with ACSL1) in adipocytes, AMP/ATP ratio measurement, and phospho-AMPK/ACC immunoblots\",\n      \"pmids\": [\"19560442\", \"20667975\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relative contribution of FATP1 versus ACSL1 to the AMP pool not separated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Revealed a non-metabolic moonlighting role: FATP1 binds RPE65 and LRAT via its cytosolic C-terminus to inhibit the retinal visual cycle.\",\n      \"evidence\": \"Yeast two-hybrid with RPE65, dose-dependent interaction with native RPE65/LRAT, and 11-cis retinol production assays in RPE\",\n      \"pmids\": [\"20356843\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological significance in vivo not established by this study\", \"Whether inhibition depends on FATP1 enzymatic activity unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Confirmed in vivo that FATP1 can channel muscle fatty acids toward oxidation rather than storage without worsening insulin resistance, distinguishing FATP1 from lipotoxic transporters.\",\n      \"evidence\": \"Muscle-specific Mck/Fatp1 transgenic mice with palmitate transport/oxidation, in vivo BMIPP uptake, and glucose tolerance tests\",\n      \"pmids\": [\"21442160\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not address adipose-specific functions\", \"Mechanism directing flux to oxidation vs esterification not defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolved that FATP1 facilitates uptake by metabolic trapping from the ER rather than direct plasma-membrane transport, and refined its retinal phenotype.\",\n      \"evidence\": \"Retroviral FATP1 overexpression in 3T3-L1 with ER co-localization/fractionation and uptake assays; Fatp1-/- retinal ERG and EM\",\n      \"pmids\": [\"23024797\", \"23166839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Apparent conflict with insulin-driven plasma-membrane translocation not fully reconciled\", \"Retinal aging mechanism (vascular vs metabolic) unresolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Localized FATP1 specifically to the mitochondrial outer membrane and intermembrane space and showed it channels muscle fatty acids to \\u03b2-oxidation while sparing ketone bodies.\",\n      \"evidence\": \"Differential fractionation plus immunogold EM of FATP1-GFP, with in vivo adenoviral overexpression and isolated muscle oxidation assays\",\n      \"pmids\": [\"24858472\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of FATP1 targeting to the outer mitochondrial membrane unknown\", \"How soluble IMS pool functions unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extended FATP1 function to immune cells, showing its acyl-CoA synthetase activity sets macrophage substrate preference and restrains pro-inflammatory activation.\",\n      \"evidence\": \"Reciprocal Fatp1-/- BMDM and FATP1-overexpressing RAW264.7 with Seahorse bioenergetics, metabolomics, and HFD bone-marrow chimeras\",\n      \"pmids\": [\"27408776\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Lipid mediators responsible for the inflammatory phenotype not pinpointed\", \"Link to the glucose/PDH axis not directly tested\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrated FATP1 mediates insulin-regulated bidirectional DHA transport at the blood-brain barrier, extending its insulin-translocation behavior to endothelium.\",\n      \"evidence\": \"FATP1 overexpression/knockdown in HEK293 and hCMEC/D3 with [14C]-DHA uptake/efflux, insulin translocation, and mouse microvessel immunohistochemistry\",\n      \"pmids\": [\"28035674\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of efflux versus influx directionality not defined\", \"Whether DHA transport requires synthetase activity untested\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Implicated FATP1 in cancer by showing it imports adipocyte-derived lipids to fuel melanoma growth and is druggable with Lipofermata.\",\n      \"evidence\": \"Co-culture lipid transfer, BRAFV600E zebrafish melanoma model, mouse xenografts, and Lipofermata inhibition\",\n      \"pmids\": [\"29903879\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream lipid signaling driving invasion not detailed\", \"Selectivity of pharmacologic inhibition for FATP1 not fully addressed\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined upstream transcriptional control of FATP1 by nuclear receptors \\u2014 ER-\\u03b2 driving and PPAR\\u03b1/\\u03b3 plus TNF-\\u03b1 suppressing expression \\u2014 tying its fatty acid uptake to hormonal and inflammatory cues.\",\n      \"evidence\": \"ER-\\u03b2 antagonist/estradiol in breast cancer lines and PPAR agonist/TNF-\\u03b1 metabolomics in macrophages, with FATP1 expression and uptake readouts\",\n      \"pmids\": [\"31575907\", \"30674874\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct transcriptional binding to the SLC27A1 promoter not shown\", \"Single-lab pharmacologic interventions\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Positioned FATP1 within an adipose browning program downstream of sympathetic Prdm16 signaling.\",\n      \"evidence\": \"In vivo iWAT siRNA knockdown of Prdm16/FATP1 with sympathetic denervation and energy expenditure measures in Withaferin A-treated mice\",\n      \"pmids\": [\"34732538\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between FATP1 fatty acid handling and browning not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed FATP1 protein at the BBB is post-translationally downregulated by iron, reducing DHA efflux.\",\n      \"evidence\": \"Ferric ammonium citrate treatment of hCMEC/D3 with RT-qPCR, Western blot, and [14C]-DHA efflux assays\",\n      \"pmids\": [\"39044044\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of iron-dependent protein turnover unknown\", \"Physiological relevance in vivo untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked FATP1-mediated LCFA transport to colorectal cancer migration/invasion via DAG-3P synthesis.\",\n      \"evidence\": \"SLC27A1 knockdown in Caco-2 and T84 cells with migration/invasion and DAG-3P pathway analysis\",\n      \"pmids\": [\"40883416\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single loss-of-function experiment without rescue or in vivo validation\", \"Mechanistic detail limited\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular machinery that reconciles FATP1's intracellular (ER/mitochondrial) localization with its insulin-stimulated plasma-membrane translocation, and the structural basis of its dual transport/synthetase activity, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of FATP1\", \"Translocation trafficking partners unidentified\", \"Whether moonlighting (RPE65/LRAT) and cancer roles require catalytic activity unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [0, 1, 4, 13, 16]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [6, 17]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [3, 5, 17]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [6, 17]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [5, 13]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [7, 8, 15]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0, 3, 6, 7, 15]},\n      {\"term_id\": \"R-HSA-382551\", \"supporting_discovery_ids\": [6, 17]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [9, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CPT1\", \"RPE65\", \"LRAT\", \"ACSL1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}