Showing papers on "Fatty acid-binding protein published in 2022"

Maternal Fatty Acid Metabolism in Pregnancy and Its Consequences in the Feto-Placental Development

Abstract: During pregnancy, maternal plasma fatty acids are critically required for cell growth and development, cell signaling, and the development of critical structural and functional aspects of the feto-placental unit. In addition, the fatty acids modulate the early stages of placental development by regulating angiogenesis in the first-trimester human placenta. Preferential transport of maternal plasma long-chain polyunsaturated fatty acids during the third trimester is critical for optimal fetal brain development. Maternal status such as obesity, diabetes, and dietary intakes may affect the functional changes in lipid metabolic processes in maternal-fetal lipid transport and metabolism. Fatty acids traverse the placental membranes via several plasma membrane fatty acid transport/binding proteins (FAT, FATP, p-FABPpm, and FFARs) and cytoplasmic fatty acid-binding proteins (FABPs). This review discusses the maternal metabolism of fatty acids and their effects on early placentation, placental fatty acid transport and metabolism, and their roles in feto-placental growth and development. The review also highlights how maternal fat metabolism modulates lipid processing, including transportation, esterification, and oxidation of fatty acids.

The Biological Functions and Regulatory Mechanisms of Fatty Acid Binding Protein 5 in Various Diseases

Abstract: In recent years, fatty acid binding protein 5 (FABP5), also known as fatty acid transporter, has been widely researched with the help of modern genetic technology. Emerging evidence suggests its critical role in regulating lipid transport, homeostasis, and metabolism. Its involvement in the pathogenesis of various diseases such as metabolic syndrome, skin diseases, cancer, and neurological diseases is the key to understanding the true nature of the protein. This makes FABP5 be a promising component for numerous clinical applications. This review has summarized the most recent advances in the research of FABP5 in modulating cellular processes, providing an in-depth analysis of the protein’s biological properties, biological functions, and mechanisms involved in various diseases. In addition, we have discussed the possibility of using FABP5 as a new diagnostic biomarker and therapeutic target for human diseases, shedding light on challenges facing future research.

Fatty acid binding protein 5 regulates lipogenesis and tumor growth in lung adenocarcinoma.

Abstract: Lung cancer is the leading cause of cancer-related death. Unfortunately, targeted-therapies have been unsuccessful for most patients with lung adenocarcinoma (LUAD). Thus, new early biomarkers and treatment options are a pressing need. Fatty acid binding protein 5 (FABP5) has been associated with various types of cancers. Its contribution to LUAD onset, progression and metabolic reprogramming is, however, not fully understood. In this study we assessed the importance of FABP5 in LUAD and its role in cancer lipid metabolism.By radioactive labeling and metabolite quantification, we studied the function of FABP5 in fatty acid metabolism using genetic/pharmacologic inhibition and overexpression models in LUAD cell lines. Flow cytometry, heterologous transplantation and bioinformatic analysis were used, in combination with other methodologies, to assess the importance of FABP5 for cellular proliferation in vitro and in vivo and in patient survival.We show that high expression of FABP5 is associated with poor prognosis in patients with LUAD. FABP5 regulates lipid metabolism, diverting fatty acids towards complex lipid synthesis, whereas it does not affect their catabolism in vitro. Moreover, FABP5 is required for de novo fatty acid synthesis and regulates the expression of enzymes involved in the pathway (including FASN and SCD1). Consistently with the changes in lipid metabolism, FABP5 is required for cell cycle progression, migration and in vivo tumor growth.Our results suggest that FABP5 is a regulatory hub of lipid metabolism and tumor progression in LUAD, placing it as a new putative therapeutic target for this disease.

Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. An update from 2017 to early 2022.

Abstract: The fatty acid binding protein 4 (FABP4) is a protein predominantly expressed in macrophages and adipose tissue, where it regulates fatty acids storage and lipolysis and is an essential mediator of inflammation. Small molecule inhibitors of FABP4 have attracted interest following the recent publications of beneficial pharmacological effects of these compounds for the treatment of metabolic syndrome and, more recently, for other pathologies. Since the synthesis of the BMS309403, one of the first selective and effective FABP4 inhibitors, hundreds of other inhibitors have been synthesized (i.e., derivatives of niacin, quinoxaline, aryl-quinoline, bicyclic pyridine, urea, aromatic compounds and other novel heterocyclic compounds). This review updates the recently reported (2017 to early 2022) molecules as adipocyte fatty acid binding protein 4 inhibitors.

Evolutionary and Association Analysis of Buffalo FABP Family Genes Reveal Their Potential Role in Milk Performance

Abstract: The fatty acid-binding protein (FABP) family gene encode a group of proteins that affect long-chain fatty acid (LCFAs) trafficking and play a crucial function in the regulation of milk fat synthesis. Nevertheless, little is known regarding the identification of members, theevolutionary background, and functional characteristics of FABP genes in buffalo. In this study, in silico analysis was performed to identify the members of FABPs in buffalo. The results revealed that a total of 17 FABP genes were identified. Based on their phylogenetic relationships, these sequences clustered into five groups with similar motif patterns and gene structures. According to positive selection analyses, all duplicated gene pairs containing FABPs in buffalo had Ka/Ks (nonsynonymous/synonymous) ratios that were less than 1, suggesting that they were under purifying selection. Association analysis showed that one SNP in LOC102401361 was found significantly associated with buffalo milk yield. The expression levels of several FABPs in buffalo mammary epithelial cells were regulated by palmitic and stearic acid treatment. The findings of this study provide valuable information for further research on the role of FABPs in regulating buffalo milk synthesis.

FABP4 in obesity-associated carcinogenesis: Novel insights into mechanisms and therapeutic implications

Abstract: The increasing prevalence of obesity worldwide is associated with an increased risk of various diseases, including multiple metabolic diseases, cardiovascular diseases, and malignant tumors. Fatty acid binding proteins (FABPs) are members of the adipokine family of multifunctional proteins that are related to fatty acid metabolism and are divided into 12 types according to their tissue origin. FABP4 is mainly secreted by adipocytes and macrophages. Under obesity, the synthesis of FABP4 increases, and the FABP4 content is higher not only in tissues but also in the blood, which promotes the occurrence and development of various cancers. Here, we comprehensively investigated obesity epidemiology and the biological mechanisms associated with the functions of FABP4 that may explain this effect. In this review, we explore the molecular mechanisms by which FABP4 promotes carcinoma development and the interaction between fat and cancer cells in obese circumstances here. This review leads us to understand how FABP4 signaling is involved in obesity-associated tumors, which could increase the potential for advancing novel therapeutic strategies and molecular targets for the systematic treatment of malignant tumors.

Fatty Acid-Binding Proteins in Psoriasis—A Review

Abstract: Psoriasis is one of the most common skin diseases in dermatological practice. It affects about 1–3% of the general population and is associated with different comorbidities, especially metabolic syndrome. Fatty-acid-binding proteins (FABPs) are a family of cytosolic proteins which are an important link in lipid metabolism and transport; moreover, they have different tissue specificity and properties. So far, ten FABPs have been discovered and seven have been investigated in psoriasis. In this review, we discuss the nature of all FABPs and their role in psoriasis. FABPs have different organ and tissue expression, and hence various functions, and may be markers of different disorders. Considering the concentration of a few of them tends to be elevated in psoriasis, it confirms the current perception of psoriasis as a multiorgan disorder associated with plenty of comorbidities. Some FABPs may be also further investigated as biomarkers of psoriasis organ complications. FABP-1 and FABP-5 may become potential markers of metabolic complications and inflammation in psoriasis. FABP-7 could perhaps be further investigated as an indicator of the neurodegenerative processes in psoriatic patients.

Structure of recombinantly expressed cockroach Lili-Mip protein in glycosylated and deglycosylated forms

Abstract: The Pacific Beetle Cockroach is the only known viviparous cockroach. The pregnant females provide nutrition to the embryos by secreting milk proteins (Lili-Mips), which crystallize in vivo. The crystals that grow in the embryo are heterogeneous in their protein sequence. It is not apparent from the structure determined what role heterogeneity and glycosylation played in crystallization. Lili-Mips are very nutritious.Here, we report the cloning of synthesized Lili-Mip genes, their expression in Saccharomyces cerevisiae as secreted proteins, purification, crystallization, and the determination of a three-dimensional structure of one glycosylated and one deglycosylated form.A 2.35 Å structure of the glycosylated form is bound to palmitoleic acid and has several Zn atom mediated interactions. A 1.45 Å structure of the deglycosylated protein reveals a binding pocket that has both oleic and palmitoleic acid bound. Mass-spectrometry shows that oleic acid and palmitoleic acid are bound to the protein. Docking studies suggest that aliphatic chains of lengths 15, 16, and 18 carbons bind well in the pocket.The recombinantly expressed and secreted protein is glycosylated, has a bound fatty acid, is homogenous in its protein sequences, and readily forms crystals. The deglycosylated protein also crystallizes readily, suggesting that the high crystallizability of this protein is independent of glycosylation.Lili-Mips belong to the ubiquitous lipocalin family of proteins that bind to a large variety of ligands. While the residues lining the barrel are essential for the affinity of the ligand, our results show the role of side-chain orientations to ligand selectivity.

Fatty Acid-Binding Proteins: Their Roles in Ischemic Stroke and Potential as Drug Targets

Abstract: Stroke is among the leading causes of death and disability worldwide. However, despite long-term research yielding numerous candidate neuroprotective drugs, there remains a lack of effective neuroprotective therapies for ischemic stroke patients. Among the factors contributing to this deficiency could be that single-target therapy is insufficient in addressing the complex and extensive mechanistic basis of ischemic brain injury. In this context, lipids serve as an essential component of multiple biological processes and play important roles in the pathogenesis of numerous common neurological diseases. Moreover, in recent years, fatty acid-binding proteins (FABPs), a family of lipid chaperone proteins, have been discovered to be involved in the onset or development of several neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. However, comparatively little attention has focused on the roles played by FABPs in ischemic stroke. We have recently demonstrated that neural tissue-associated FABPs are involved in the pathological mechanism of ischemic brain injury in mice. Here, we review the literature published in the past decade that has reported on the associations between FABPs and ischemia and summarize the relevant regulatory mechanisms of FABPs implicated in ischemic injury. We also propose candidate FABPs that could serve as potential therapeutic targets for ischemic stroke.

The Correlations of Plasma Liver-Type Fatty Acid-Binding Protein with Amyloid-β and Tau Levels in Patients with Alzheimer's Disease.

Abstract: BACKGROUND The dysregulation of lipid metabolism plays an important role in the pathogenesis of Alzheimer's disease (AD). Liver-type fatty acid-binding protein (L-FABP, also known as FABP1) is critical for fatty acid transport and may be involved in AD. OBJECTIVE To investigate whether the FABP1 level is altered in patients with AD, and its associations with levels of amyloid-β (Aβ) and tau in the plasma and cerebrospinal fluid (CSF). METHODS A cross-sectional study was conducted in a Chinese cohort consisting of 39 cognitively normal controls and 47 patients with AD. The levels of FABP1 in plasma, and Aβ and tau in CSF, were measured by enzyme-linked immunosorbent assay (ELISA). A single-molecule array (SIMOA) was used to detect plasma Aβ levels. RESULTS The level of plasma FABP1 was significantly elevated in the AD group (p = 0.0109). Further analysis showed a positive correlation of FABP1 with CSF total tau (t-tau) and phosphorylated tau (p-tau) levels. Besides, plasma FABP1/Aβ 42 (AUC = 0.6794, p = 0.0071) and FABP1/t-tau (AUC = 0.7168, p = 0.0011) showed fair diagnostic efficacy for AD. When combined with other common AD biomarkers including plasma Aβ 42, Aβ 40, and t-tau, both FABP1/Aβ 42 and FABP1/t-tau showed better diagnostic efficacy than using these biomarkers alone. Among all AUC analyses, the combination of plasma FABP1/t-tau and Aβ 42 had the highest diagnostic value (AUC = 0.8075, p < 0.0001). CONCLUSION These findings indicate that FABP1 may play a role in AD pathogenesis and be worthy of further investigation in the future.

Characterization of the fatty acid binding protein 3 (FABP3) promoter and its transcriptional regulation by cAMP response element binding protein 1 (CREB1) in goat mammary epithelial cells.

Abstract: Fatty acid binding protein 3 (FABP3) is involved in signal transduction pathways, and in the uptake and utilization of long-chain fatty acids. However, the transcriptional regulation of FABP3 in goat is unclear. In this study, the FABP3 5' flanking region was amplified from goat (Capra hircus) genomic DNA. Luciferase reporter vectors containing promoter fragments of five different lengths were constructed and transfected into dairy goat mammary epithelial cells. The region of the promoter located between -1801 and -166 bp upstream of the transcription start site (TSS) exhibited the highest luciferase activity, and contained two cAMP response elements (CREs) located at -1632 bp and -189 bp. Interference with CREB1 significantly downregulated FABP3 promoter activity. In addition, FABP3 promoter activity was significantly reduced after mutation of the CRE1 (-1632 bp) and CRE2 (-189 bp) sites. Further analysis indicated that the CRE2 site was essential for the transcriptional activity induced by CREB1. These results demonstrated that CREB1 is involved in the transcriptional regulation of FABP3 expression in the goat mammary gland via a direct mechanism, thus revealing a novel signaling pathway involved in fatty acid metabolism in goat.

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Abstract: Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.

Changes in median eminence of fatty acid–binding protein 3 in a mouse model of pain

Abstract: Fatty acid–binding protein (FABP) regulates polyunsaturated fatty acid (PUFA) intracellular trafficking and signal transduction. Our previous studies demonstrated that the alteration of PUFA in the hypothalamus is involved in pain process. However, how FABP subtypes change during pain remain unclear. Here, we examined the expression changes and localization in the hypothalamic FABP subtype in postoperative pain model mice.

Therapeutic Implications of FABP4 in Cancer: An Emerging Target to Tackle Cancer

Abstract: Metabolic reprogramming is an emerging hallmark of tumor cells. In order to survive in nutrient-deprived environment, tumor cells rewire their metabolic phenotype to provide sufficient energy and build biomass to sustain their transformed state and promote malignant behaviors. Fatty acid uptake and trafficking is an essential part of lipid metabolism within tumor cells. Fatty acid-binding proteins (FABPs), which belongs to a family of intracellular lipid-binding protein, can bind hydrophobic ligands to regulate lipid trafficking and metabolism. In particular, adipocyte fatty acid binding protein (FABP4), one of the most abundant members, has been found to be upregulated in many malignant solid tumors, and correlated with poor prognosis. In multiple tumor types, FABP4 is critical for tumor proliferation, metastasis and drug resistance. More importantly, FABP4 is a crucial driver of malignancy not only by activating the oncogenic signaling pathways, but also rewiring the metabolic phenotypes of tumor cells to satisfy their enhanced energy demand for tumor development. Thus, FABP4 serves as a tumor-promoting molecule in most cancer types, and may be a promising therapeutic target for cancer treatment.

A unique, newly discovered four-member protein family involved in extracellular fatty acid binding in Yarrowia lipolytica

Abstract: Yarrowia lipolytica, a nonconventional oleaginous yeast species, has attracted attention due to its high lipid degradation and accumulation capacities. Y. lipolytica is used as a chassis for the production of usual and unusual lipids and lipid derivatives. While the genes involved in the intracellular transport and activation of fatty acids in different cellular compartments have been characterized, no genes involved in fatty acid transport from the extracellular medium into the cell have been identified thus far. In this study, we identified secreted proteins involved in extracellular fatty acid binding.Recent analysis of the Y. lipolytica secretome led to the identification of a multigene family that encodes four secreted proteins, preliminarily named UP1 to UP4. These proteins were efficiently overexpressed individually in wild-type and multideletant strain (Q4: Δup1Δup2Δup3Δup4) backgrounds. Phenotypic analysis demonstrated the involvement of these proteins in the binding of extracellular fatty acids. Additionally, gene deletion and overexpression prevented and promoted sensitivity to octanoic acid (C8) toxicity, respectively. The results suggested binding is dependent on aliphatic chain length and fatty acid concentration. 3D structure modeling supports the proteins' role in fatty acid assimilation at the molecular level.We discovered a family of extracellular-fatty-acid-binding proteins in Y. lipolytica and have proposed to name its members eFbp1 to eFbp4. The exact mode of eFbps action remains to be deciphered individually and synergistically; nevertheless, it is expected that the proteins will have applications in lipid biotechnology, such as improving fatty acid production and/or bioconversion.

Tissue Distribution and Nutritional Regulation of Fatty Acid-Binding Proteins (fabps) in Two Marine Teleosts, Turbot (Scophthalmus maximus), and Tiger Puffer (Takifugu rubripes)

Abstract: Fatty acid-binding proteins (fabps) play important roles in lipid homeostasis. In the present study, 7 fabp isoforms, namely, fabp1, fabp2, fabp3, fabp4, fabp6, fabp7, and fabp10, in two marine teleosts, were characterized. In general, turbot and tiger puffer fabp genes showed high identity to their orthologs in other fish species and mammals, but tiger puffer Fabp6 shared the lowest identity to its known orthologs in zebrafish and human. The tissue distribution patterns of fabps were generally in accordance with their function features. However, tiger puffer fabps, in particular Fabp1, Fabp2, Fabp6 and Fabp7, may have functions distinct from other teleosts, as indicated by the phylogenetic tree and tissue distribution patterns. In both species, high dietary lipid levels downregulated the expression of fabp2, fabp3, fabp6, and fabp7a but tended to upregulate the fabp1 expression. Starvation downregulated the expression of most fabps in both fish species, but the downregulation of fabp expression in turbot was much more drastic and earlier compared to tiger puffer. Long-term (30-day) starvation increased the fabp7 expression in tiger puffer and tended to increase the fabp6 expression in turbot. Results of this study contribute to fish fabp physiology and its nutritional regulation.

Structural Insights into Mouse H-FABP

Abstract: Intracellular fatty acid-binding proteins are evolutionarily highly conserved proteins. The major functions and responsibilities of this family are the regulation of FA uptake and intracellular transport. The structure of the H-FABP ortholog from mouse (Mus musculus) had not been revealed at the time this study was completed. Thus, further exploration of the structural properties of mouse H-FABP is expected to extend our knowledge of the model animal’s molecular mechanism of H-FABP function. Here, we report the high-resolution crystal structure and the NMR characterization of mouse H-FABP. Our work discloses the unique structural features of mouse H-FABP, offering a structural basis for the further development of small-molecule inhibitors for H-FABP.

Fatty acid-binding proteins 3 and 5 are involved in the initiation of mitochondrial damage in ischemic neurons

Abstract: We have previously shown that a fatty acid-binding protein7 (FABP7) inhibitor ameliorates cerebral ischemia-reperfusion injury in mice, suggesting an association between FABPs and ischemic neuronal injury. However, the precise role of FABPs in ischemic neuronal injury remains unclear. In this study, we investigated the role of FABPs in ischemia-reperfusion neuronal injury. FABP3, FABP5, and FABP7 were upregulated in the ischemic penumbra regions in mice. However, only FABP3 and FABP5 were expressed in injured neurons. Furthermore, FABP3 and FABP5 accumulated in the mitochondria of ischemic neurons. Overexpressing either FABP3 or FABP5 aggravated the reduced mitochondrial membrane potential and induced cell death in human neuroblastoma SH-SY5Y cells during oxidative stress. This damage was mediated by the formation of BAX-containing pores in the mitochondrial membrane. Moreover, FABP5 mediates lipid peroxidation and generates toxic by-products (i.e., 4-HNE) in SH-SY5Y cells. HY11-08 (HY08), a novel FABP3 and 5 inhibitor that does not act on FABP7, significantly reduced cerebral infarct volume and blocked FABP3/5-induced mitochondrial damage, including lipid peroxidation and BAX-related apoptotic signaling. Thus, FABP3 and FABP5 are key players in triggering mitochondrial damage in ischemic neurons. In addition, the novel FABP inhibitor, HY08, may be a potential neuroprotective treatment for ischemic stroke.

Co-overexpression of CD36 and FABPpm increases fatty acid transport additively, not synergistically, within muscle.

Abstract: We aimed to determine the combined effects of over-expressing FABPpm and CD36 on skeletal muscle fatty acid transport to establish if these transport proteins function collaboratively. Electrotransfection with either FABPpm or CD36 increased their protein content at the plasma membrane (+75% and +64%), increased fatty acid transport rates +24% for FABPpm and +62% for CD36, resulting in a calculated transport efficiency of ~0.019 and ~0.053 per unit protein change for FABPpm and CD36, respectively. We subsequently used these data to determine if increasing both proteins additively or synergistically increased fatty acid transport. Co-transfection of FABPpm and CD36 simultaneously increased protein content in whole muscle (FABPpm, +46%; CD36, +45%) and at the sarcolemma (FABPpm, +41% and CD36, +42%), as well as fatty acid transport rates (+50%). Since the relative effects of changing FABPpm and CD36 content had been independently determined, we were able to a predict a change in fatty acid transport based on the overexpression of plasmalemmal transporters in the co-transfection experiments. This prediction yielded an increase in fatty acid transport of +0.984 and +1.722 pmol/mg prot/15sec for FABPpm and CD36, respectively, for a total increase of +2.96 pmol/mg prot/15sec. This calculated determination was remarkably consistent with the measured change in transport, namely +2.89 pmol/mg prot/15sec. Altogether, these data indicate that increasing CD36 and FABPpm alters fatty acid transport rates additively, but not synergistically, suggesting an independent mechanism-of-action within muscle for each transporter. This conclusion was further supported by the observation that plasmalemmal CD36 and FABPpm did not co-immunoprecipitate.

The covalent reactivity of functionalized 5-hydroxy-butyrolactams is the basis for targeting of fatty acid binding protein 5 (FABP5) by the neurotrophic agent MT-21

Abstract: Covalently acting compounds experience a strong interest within chemical biology both as molecular probes in studies of fundamental biological mechanisms and/or as novel drug candidates. In this context, the identification of new classes of reactive groups is particularly important as these can expose novel reactivity modes and, consequently, expand the ligandable proteome. Here, we investigated the electrophilic reactivity of the 3-acyl-5-hydroxy-1,5-dihydro-2H-pyrrole-2-one (AHPO) scaffold, a heterocyclic motif that is e.g. present in various bioactive natural products. Our investigations were focused on the compound MT-21 – a simplified structural analogue of the natural product epolactaene – which is known to have both neurotrophic activity and ability to trigger apoptotic cell death. We found that the central N-acyl hemiaminal group of MT-21 can function as an electrophilic centre enabling divergent reactivity with both amine- and thiol-based nucleophiles, which furthermore translated to reactivity with proteins in both cell lysates and live cells. We found that in live cells MT-21 strongly engaged the lipid transport protein fatty acid-binding protein 5 (FABP5) by direct binding to a cysteine residue in the bottom of the ligand binding pocket. Through preparation of a series of MT-21 derivatives, we probed the specificity of this interaction which was found to be strongly dependent on subtle structural changes. Our study suggests that MT-21 may be employed as a tool compound in future studies of the biology of FABP5, which remains incompletely understood. Furthermore, our study has also made clear that other natural products containing the AHPO-motif may likewise possess covalent reactivity and that this property may underlie their biological activity.

The proximal intestinal Fatty Acid-Binding Proteins liver FABP (LFABP) and intestinal FABP (IFABP) differentially modulate whole body energy homeostasis but are not centrally involved in net dietary lipid absorption: Studies of the LFABP/IFABP double knockout mouse.

Abstract: Proximal intestinal enterocytes expresses both intestinal-fatty acid binding protein (IFABP; FABP2) and liver-FABP (LFABP; FABP1). These FABPs are thought to be important in the net uptake of dietary lipid from the intestinal lumen, however their specific and potentially unique functions in the enterocyte remain incompletely understood. We previously showed markedly divergent phenotypes in LFABP-/- vs. IFABP-/- mice fed high-fat diets, with the former becoming obese and the latter remaining lean relative to wild-type (WT) mice, supporting different functional roles for each protein. Interestingly, neither mouse model displayed increased fecal lipid concentration, raising the question of whether the presence of one FABP was sufficient to compensate for absence of the other. Here, we generated an LFABP and IFABP double knockout mouse (DKO) to determine whether simultaneous ablation would lead to fat malabsorption, and to further interrogate the individual vs. overlapping functions of these proteins. Male WT, IFABP-/-, LFABP-/-, and DKO mice were fed a low-fat (10 % kcal) or high-fat (45 % kcal) diet for 12 weeks. The body weights and fat mass of the DKO mice integrated those of the LFABP-/- and IFABP-/- single knockouts, supporting the notion that IFABP and LFABP have distinct functions in intestinal lipid assimilation that result in downstream alterations in systemic energy metabolism. Remarkably, no differences in fecal fat concentrations were found in the DKO compared to WT, revealing that the FABPs are not required for net intestinal uptake of dietary lipid.