The expression of the putative membrane fatty-acid transporter (FAT) was investigated in the small intestine. The FAT mRNA level was higher in the jejunum than in the duodenum and was lower in the ileum, as observed for cytosolic fatty-acid-binding proteins (FABP) expressed in this tissue. No FAT transcript was found in the stomach or colon. FAT mRNA was constitutively expressed i n the epithelial cells located in the upper two thirds of villi, while it was undectectable in the crypt cells and submucosal cells. In jejunal mucosa, immunochemical studies showed that FAT protein was limited to the brush border of enterocytes. No fluorescence was found in the goblet cells. To determine whether FAT responded to changes in fat intake, as reported for FABP, the effect of two high-fat diets, which essentially contained either medium-chain fatty acids or long-chain fatty acids (sunflower-oil diet), was investigated. The sunflower-oil diet greatly increased FAT mRNA abundance throughout the small intestine. In contrast, a weak effect of medium-chain fatty acids was observed only in the jejunum. As found for FABP expression, treatment with the hypolipidemic drug bezafibrate affected FAT expression. These data demonstrate that FAT and FABP are co-expressed in enterocytes, as has been shown in adipocytes, myocytes and mammary cells. The data suggest that these membrane and cytosolic proteins might have complementary functions during dietary-fat absorption.Keywords: fatty-acid transporter ; fatty-acid-binding protein ; small intestine ; gene regulation ; lipid.How long-chain fatty acids (LCFA) move across the biological membranes is subject to controversy. Because of their lipophilic character, they were expected to diffuse freely through the plasma membrane of cells [I]. However, this concept was challenged by the finding of a rapid and saturable uptake, which was reduced by prior heat denaturation or protease treatment of cells 121, and by the isolation and characterization of several plasma-membrane proteins that showed high affinity for LCFA [2-51. The small intestine might express at least two of these proteins: the plasma-membrane fatty-acid-binding protein (FABP) and the fatty-acid transporter (FAT) [6]. The plasmamembrane FABP is a 40-kDa protein postulated to mediate fatty acid uptake through an active sodium-dependent process in the gut 17, 81. The regulation of this protein is unknown since it has not been cloned. FAT is a 88-kDa membrane protein, which was cloned recently in adipocytes, where it might be involved in the sequestration and uptake of fatty acids 191. This protein, which is similar to the CD36 glycoprotein [lo], was detected by means of Northern blot analysis in various tissues including the small intestine [9].Once within the cell, LCFA bind to 14-1 5-kDa cytosolic proteins termed fatty-acid-binding proteins (FABP), which are thought to be involved in facilitation of LCFA desorption from the plasma membrane and diffusion of LCFA through the cytosol [ll]. Several recent reports showed that the express...