Molecular cloning of fatty acid-transport protein cDNA from rat

Schaap, Frank G.; Hamers, Lars; Vusse, Ger J.; Glatz, Jan F. C.

doi:10.1016/s0167-4781(97)00121-8

Cited by 37 publications

(24 citation statements)

References 13 publications

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“…The family of FATPs (gene name: solute carrier family 27, Slc27) is comprised of six related members in humans and mice (FATP1 to FATP6) that differ widely in their tissue expression patterns (FIGURE 2B N-terminus facing the outside of the cell and an intracellular C-terminus (52,74). Based on overall sequence similarity (83,85), it is likely that these basic characteristics will hold true for other FATP family members as well.…”

Section: Fatpsmentioning

confidence: 99%

Protein-Mediated Fatty Acid Uptake: Novel Insights from In Vivo Models

Doege¹,

2006

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Long-chain fatty acids (LCFAs) are vital components of our diet and contribute to a plethora of processes including metabolic energy generation and storage, plasma membrane synthesis, and protein anchoring. In addition, LCFAs have hormone-like properties since they can profoundly affect gene expression via nuclear receptors such as HNF4 and the PPAR family (reviewed in Ref. 45), trigger insulin release through activation of the G-protein-coupled receptor (GPCR) GPR40 by ␤-cells (89), affect the innate immune response by modulating toll-like receptor (TLR) signaling in a number of cell types (reviewed in Ref. 53), and suppress food intake by inhibiting the release of neuropeptide Y (NPY) and Agouti-related protein (AgRP) in a subpopulation of hypothalamic neurons (reviewed in Refs. 51, 78). Because of the physiological significance of LCFAs, chronic imbalances in lipid fluxes and metabolism often cause a variety of (metabolic) abnormalities and pathologies, including hyperlipidemia, obesity, Type 2 diabetes mellitus, nonalcoholic fatty liver disease, heart disease, and cancer (16,37,50,54,56,57,64,73).Although in some tissues and cell types LCFAs can signal through GPCRs or TLRs (53, 89), they typically have to first cross the plasma membrane to elicit their effects. In general, the uptake of fatty acids from the circulation into cells include the sequence of 1) localized generation of free fatty acids through hydrolysis of triglyceride (TG)-rich lipoproteins by lipases inside the endothelial lumen and binding of fatty acids to albumin, 2) fatty acid dissociation from albumin followed by binding to plasma membrane proteins or integration into the lipid bilayer, 3) their transport across the plasma membranes, and 4) their intracellular association with fatty acid binding and acyl-CoA binding proteins (FABPs and ACBPs, respectively) (1, 33, 91), as illustrated in FIGURE 1A. The mechanism by which fatty acids cross the plasma membrane has been debated for several years. Because fatty acids are predominantly lipophilic, it was initially proposed that they traverse the lipid bilayer by diffusion (passive flip-flop) without the involvement of protein mediators (35,68). However, many organs and cell types display a rapid, saturable, substrate-specific, and hormonally regulated LCFA uptake mechanism indicative of protein-mediated processes (8,10,83). Although the occurrence of both LCFA uptake processes are now widely accepted, during the past years considerable data have demonstrated that protein-mediated transport accounts for the majority of fatty acid uptake by tissues with high LCFA metabolism and storage such as skeletal muscle (99), adipose tissue (75), liver (22,24,26,82,93,95), and heart (81, 94). Particularly, at physiological concentrations and serum-to-albumin ratios, the concentration of unbound fatty acids is low (7.5 nM) and >90% of LCFA uptake occurs via the protein-mediated pathway (71). The crucial role of proteins for efficient LCFA uptake has been underscored by a number of knockout (KO) model systems...

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Section: Fatpsmentioning

confidence: 99%

Protein-Mediated Fatty Acid Uptake: Novel Insights from In Vivo Models

Doege¹,

2006

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“…Based on the primary amino acid sequence, models with one to four transmembrane domains have been proposed [21,32]. The exact number of transmembrane domains, however, is difficult to predict due to the hydrophobic nature of a protein that interacts strongly with fatty acids.…”

Section: Fatp Structure and Substratesmentioning

confidence: 99%

“…3A), six FATP genes have been identified in human and mouse genomes (FATP1-6) [2,3,11,17,32,33,36,39,46]. The phylogenetic relationship among the six human and murine family members is shown as an unrooted tree in Fig.…”

Section: Introductionmentioning

confidence: 99%

A current review of fatty acid transport proteins (SLC27)

Stahl

2004

Pfl�gers Archiv European Journal of Physiology

257

201

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Long-chain fatty acids (LCFAs) are not only important metabolites but contribute to many cellular functions including activation of protein kinase C (PKC) isoforms and nuclear transcription factors such as peroxisome proliferator-activated receptors (PPAPs). To assert their diverse effects LCFAs have first to traverse the plasma membrane, a process that can occur either through diffusion or be mediated by proteins. Considerable evidence has accumulated to show that in addition to a diffusional component, the intestine, heart, adipose tissue, and the liver express a saturable and specific LCFA transport system. Identifying the postulated fatty acid transporters is of considerable importance, since both increased and decreased fatty acid uptake have been implicated in diseases such as type-2 diabetes and acute liver failure. Fatty acid transport proteins (FATPs/solute carrier family 27) are integral transmembrane proteins that enhance the uptake of long-chain and very long chain fatty acids into cells. In humans FATPs comprise a family of six highly homologous proteins, hsFATP1-6, which are found in all fatty acid-utilizing tissues of the body. This review will focus on a brief discussion of FATP expression patterns, regulation, structure, and mechanism of transport.

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“…Based on the primary amino acid sequence, models with one to four transmembrane domains have been proposed (Schaap et al, 1997;Lewis et al, 2001). The exact number of transmembrane domains, however, is difficult to predict due to the hydrophobic nature of a protein that interacts strongly with fatty acids.…”

Section: Analysis Of the Deduced Amino Acid Sequencementioning

confidence: 99%

Structural and functional characterization of the bovine solute carrier family 27 member 1 <i>(SLC27A1)</i> gene

Ordovás¹,

Roy²,

Zaragoza³

et al. 2006

Cytogenet Genome Res

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The Solute Carrier Family 27 Member 1 (SLC27A1) is an evolutionarily conserved protein involved in regulating the long chain fatty acid uptake into cells. It has been shown to be expressed in tissues undergoing rapid fatty acid metabolism such as heart, skeletal muscle and adipose tissues, but no expression is detected in liver. Here we report the molecular characterization of the bovine SLC27A1 gene and draw a comparison with orthologous genes of some monogastric species. The bovine SLC27A1 gene is organized in 13 exons and extends over more than 40 kb of genomic DNA. It codes for a protein of 646 amino acids with a predicted molecular weight of 71 kDa which has 92%, 88% and 88% similarity with the human, mouse and rat SLC27A1 proteins respectively. The bovine SLC27A1 RNA expression was high in heart, testis, nervous tissue and muscle and very low in liver. Surprisingly, adipose tissues showed very low RNA expression levels contrary to the results described for both human and mouse genes. On the other hand, discordances observed between the bovine SLC27A1 RNA and protein expression patterns suggest that complex regulation mechanisms may be involved in determining the final SLC27A1 protein levels in each tissue. Finally, we have identified an alternative transcript generated by exon skipping of exon 3 to 7 which could encode a cytosolic SLC27A1 isoform of ∼37 kDa.

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Molecular cloning of fatty acid-transport protein cDNA from rat

Cited by 37 publications

References 13 publications

Protein-Mediated Fatty Acid Uptake: Novel Insights from In Vivo Models

Protein-Mediated Fatty Acid Uptake: Novel Insights from In Vivo Models

A current review of fatty acid transport proteins (SLC27)

Structural and functional characterization of the bovine solute carrier family 27 member 1 <i>(SLC27A1)</i> gene

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