Fatty acid transport protein family (FATP family) (FATP)

The Fatty acid transport protein (FATP) family, also known as the Solute carrier family 27 (SLC27), consists of six transmembrane proteins (FATP1–6) that facilitate the cellular uptake of long-chain fatty acids (LCFAs) (Stahl et al., 2001, Trends Endocrinol Metab). These proteins are unique bifunctional transporters that also possess intrinsic very long-chain acyl-CoA synthetase (VLCAS) activity, which activates fatty acids into thioesters to prevent their efflux from the cell (Anderson and Stahl, 2013, Mol Aspects Med). FATP members are expressed in a tissue-specific manner, with FATP1 prominent in adipose tissue and muscle, FATP2 and FATP5 in the liver, and FATP4 in the intestine and skin (Schaffer and Lodish, 1994, Cell). Dysregulation of FATP expression is closely linked to metabolic disorders such as obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD), where excessive fatty acid uptake leads to lipotoxicity (Pei et al., 2017, JCI Insight). Pharmacological inhibition of FATP2 has shown promise in reducing hepatic steatosis and improving glucose tolerance, while also emerging as a novel strategy in oncology to suppress myeloid-derived suppressor cell activity (Veglia et al., 2019, Nature). However, therapeutic targeting must account for potential safety concerns, such as the skin barrier defects observed in FATP4 deficiency, which causes Ichthyosis Prematurity Syndrome (Khnykin et al., 2011, J Lipid Res). Overall, the FATP family represents a critical node in lipid metabolism with significant potential for treating metabolic and inflammatory diseases.

Other names

Solute carrier family 27SLC27 familyVery long-chain acyl-CoA synthetaseVLCAS

Inhibition of long-chain fatty acid transport across the plasma membrane and suppression of very long-chain acyl-CoA synthetase (VLCAS) enzymatic activity, thereby reducing intracellular lipid accumulation and lipotoxicity (Pei et al., 2017, JCI Insight).