Disease relevance of SLC27A1

• In the liver, where FA oxidation is decreased during sepsis but the uptake of peripherally derived FA is increased to support reesterification, LPS decreased FATP mRNA expression by 70-80% but increased FAT mRNA levels by four- to fivefold [1].
• Fatty acid transport by the lipophilic bacterium Nocardia asteroides [2].
• Other transport processes across the mitochondrial membrane are also changed by hyperthyroidism, e.g. long chain fatty acid transport via carnitine acyl transferase, and oxaloacetate transport via substrate shuttles [3].
• Fatty acid transport is an important process in cellular energy distribution and storage in both normal and pathological states, especially obesity-linked type 2 diabetes mellitus [4].
• Fatty acid transport in multiple carboxylase deficiency fibroblasts [5].

High impact information on SLC27A1

• Here, we show that fatty acid transport protein (FATP)1 is expressed on the plasma membrane of BAT and is upregulated in response to cold stimuli, concomitant with an increase in the rate of fatty acid uptake [6].
• Stimulation of fatty uptake by isoproterenol required both protein kinase A and mitogen-activated kinase signaling and is completely dependent on FATP1 expression, as small-hairpin RNA-mediated knock down of FATP1 abrogated the effect [6].
• Fatty Acid transport protein 1 is required for nonshivering thermogenesis in brown adipose tissue [6].
• Similarly, FATP1 is expressed by the BAT-derived cell line HIB-1B upon differentiation, and both fatty acid uptake and FATP1 protein levels are rapidly elevated following isoproterenol stimulation [6].
• As a consequence, FATP1 knockout (KO) animals display smaller lipid droplets in BAT and fail to defend their core body temperature at 4 degrees C, despite elevated serum free fatty acid levels [6].

Chemical compound and disease context of SLC27A1

• Conduction disorders and atrial tachycardias were observed in patients with defects of long-chain fatty acid transport across the inner mitochondrial membrane (carnitine palmitoyl transferase type II deficiency and carnitine acylcarnitine translocase deficiency) and in patients with trifunctional protein deficiency [7].

Biological context of SLC27A1

• The FATP gene maps to chromosome 19p13.1 by fluorescence in situ hybridization, a region previously suggested to be implicated in the determination of small dense low-density lipoprotein (LDL) [8].
• The human FATP-1 gene has 12 exons and extends over more than 13 kb of genomic DNA [8].
• These findings suggest that through regulation of NEFA trafficking, FATP1 might play a role in post-prandial lipid metabolism and development of cardiovascular disease [9].
• The protein levels of the cardiac fatty acid transporters were reduced in the infarcted rat heart; FAT/CD36 by 36%, FABPpm by 12%, FATP6 by 21% and FATP1 by 26%, and the cytosolic fatty acid binding protein (cFABP) was 47% lower than in sham-operated rat hearts [10].
• PPAR-alpha activators increase hepatic uptake and the esterification of free fatty acids by stimulating the fatty acid transport protein and acyl-CoA synthetase expression [11].

Anatomical context of SLC27A1

• We have demonstrated, for the first time, that transcripts of all three putative LCFA transporters (FAT mRNA, FATP mRNA, and mAspAT/FABPpm mRNA) are present in human skeletal muscle [12].
• Muscle and adipose tissue have the highest levels of FATP-1 mRNA, small intestine has intermediate levels, and FATP-1 mRNA is barely detectable in liver [8].
• Fatty acid transport was also measured in vitro over 20 to 120 s in isolated adipocytes and cardiomyocytes obtained from SHR and from a congenic line (SHRchr4) that incorporates a piece of chromosome 4 containing wild-type CD36 [13].
• The fatty acid transport protein (FATP) family has been named according to its proposed function in mediating this process at the plasma membrane [14].
• However, the mRNA expression of FATP-1 and FATP-4 in placenta was correlated with DHA in both maternal plasma and placental phospholipids, although only FATP-4 expression was significantly correlated with DHA in cord blood phospholipids [15].

Associations of SLC27A1 with chemical compounds

• FATP1 channels exogenous FA into 1,2,3-triacyl-sn-glycerol and down-regulates sphingomyelin and cholesterol metabolism in growing 293 cells [16].
• Enhanced myocardial glucose use in patients with a deficiency in long-chain fatty acid transport (CD36 deficiency) [17].
• Toward that end, we determined the activities of key enzymes in the pathway of TG synthesis, the rates of uptake of fatty acids by adipocytes, mRNA and protein levels of the fatty acid-transporting proteins FAT/CD36 and FATP, and mRNA and protein levels of PPARgamma in omental fat of AAW and CAW [18].
• It is proposed that FATP indirectly enhance LCFA uptake by activating VLCFA to their CoA esters, which are required to maintain the typical structure of lipid rafts in cellular membranes [19].
• The effects of LPS on FATP and FAT mRNA levels in liver were observed as early as 4 h after administration and were maximal by 16 h [1].

Other interactions of SLC27A1

• Biosynthesis of lipids was investigated in growing 293 cells stably expressing fatty acid (FA) transport protein 1 (FATP1), a bifunctional polypeptide with FA transport as well as fatty acyl-CoA synthetase activity [16].
• CONCLUSIONS: Correlation of the mRNA expression of the membrane placental proteins FATP-1 and especially of FATP-4 with maternal and cord DHA leads us to conclude that these lipid carriers are involved in placental transfer of long-chain polyunsaturated fatty acids [15].
• Released into circulation as non-esterified fatty acids by lipoprotein lipase, those are taken up by adipose tissue via specific plasma fatty acid transporters (CD36, FATP, FABPpm) and used for triacylglycerol synthesis [20].
• TNF and IL-1 mimicked the effect of LPS on FATP and FAT mRNA levels in both liver and adipose tissue [1].
• On the basis of fine mapping of a quantitative trait loci region of BTA3 for milk fat content, an examination of the comparative map between cattle and human indicates that the annexin 9 protein gene (ANXA9) and the fatty acid transport protein type 3 gene (SLC27A3) are two strong candidate genes [21].

References