SLC27A1 Membrane Protein Introduction

Introduction of SLC27A1

SLC27A1 is encoded by the SLC27A1 or FATP1 gene and is also known as Long-chain fatty acid transport protein 1, FATP-1 and Fatty acid transport protein 1. It is a member of the FATP/SLC27 protein family, enhances the cellular uptake of long-chain fatty acids (LCFAs) and is expressed in several insulin-sensitive tissues. Six FATP genes are found in human and mouse genomes (FATP1 through -6, Slc271 to -6). SLC27A1 was the first family member identified and is thus far the best studied. Human SLC27A1 is a 71-kDa transmembrane protein and is the major FATP in adipose tissue.

Function of SLC27A1 Membrane Protein

SLC27A1 is an ideal candidate for limiting pro-inflammatory activation: SLC27A1 is an acyl-CoA synthetase with affinity for long and very long chain fatty acids lending specificity to its function, which is important because some macrophage fatty acid transporters, such as CD36, are promiscuous. SLC27A1 expression levels are highest in tissues characterized by active fatty acid uptake and lipid metabolism, such as adipose, heart, and skeletal muscle and is primarily localized to the plasma membrane, mitochondria, and peroxisomes. In adipocytes, SLC27A1 activity is regulated by insulin-mediated translocation that increases fatty acid uptake. Studies of total-body Fatp1 knockout mice demonstrated that loss of SLC27A1 protected mice from the effects of HFD-induced obesity, insulin resistance, and intramuscular lipid accumulation. Functional characterization of SLC27A1 and activation of fatty acids through its ACSL activity have been conducted in these tissues and cell types, but, to date, not in macrophages. Due to its complex expression pattern, the contribution of FATP1 to the development of insulin resistance is likely to be tissue- and cell-type specific.

Fig.1 SLC27A1 is a novel regulator of macrophage activation. (Johnson, 2016)

Application of SLC27A1 Membrane Protein in Literature

1. Johnson A.R., et al. Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. Molecular Metabolism. 2016, 5(7):506-526. PubMed ID: 27408776
   
   

   This article demonstrates that SLC27A1 is involved in regulating the inflammatory tone of adipose and systemic metabolism for the first time. The data of this article point out SLC27A1 may be a novel regulator of macrophage activation through control of substrate metabolism.

2. Wu Q., et al. FATP1 Is an Insulin-Sensitive Fatty Acid Transporter Involved in Diet-Induced Obesity. Mol. Cell. Biol. 2016, 26(9):3455-3467. PubMed ID: 16611988
   
   

   This article reveals that the SLC27A1 activation can regulate the uptake of LCFA by tissues via insulin and the tissue distribution of dietary lipids is also related to SLC27A1 for the first time. In the SLC27A1-null mice, the strong protection against diet-induced obesity and insulin desensitization are observed, suggesting SLC27A1 as a novel antidiabetic target.

3. Cubizolle A., et al. Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina. PLoS ONE. 2017, 12(7):e0180148. PubMed ID: 28672005
   
   

   The data in this article show that SLC27A1 mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development for the first time.

4. Nishiyama K., et al. Fatty acid transport protein 1 enhances the macrophage inflammatory response by coupling with ceramide and c-Jun N-terminal kinase signaling. Int. Immunopharmacol. 2018, 55:205-215. PubMed ID: 29272817
   
   

   This article reports that SLC27A1 and the inflammatory response signaling pathway are linked in the macrophage. Fatty acid uptake through SLC27A1 regulates the inflammatory cytokines through ceramide and JNK signaling in the macrophages. Meanwhile, an inhibitor of SLC27A1 attenuated the production of inflammatory cytokines in an LPS-induced lung injury in vivo mouse model.

5. Zhao L., et al. Lack of myeloid Fatp1 increases atherosclerotic lesion size in Ldlr^-/- mice. Atherosclerosis. 2017, 266:182-189. PubMed ID: 29035781
   
   

   Authors in this article transplant bone marrow collected from Fatp1^+/+ or Fatp1^-/- mice into Ldlr^-/- mice and these mice exhibited significantly larger lesion area and elevated oxidative stress and inflammation in the atherosclerotic plaque, suggesting that macrophage SLC27A1 limits atherogenesis and may be a viable target to metabolically reprogram macrophages.

SLC27A1 Preparation Options

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Reference

1. Johnson A R., et al. (2016) Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. Molecular Metabolism. 5(7):506-526.

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