Localization and Regulation of the Putative Membrane Fatty‐Acid Transporter (FAT) in the Small Intestine

Abstract

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...

CD36 Is Important for Chylomicron Formation and Secretion and May Mediate Cholesterol Uptake in the Proximal Intestine

“…The radioactive [9, H(N)] triolein (labels were on the 3 FA molecules, not on the glycerol moiety) and [4][5][6][7][8][9][10][11][12][13][14] C] cholesterol were purchased from New England Nuclear (Boston, MA). Silica gel 60 plates were purchased from Fisher Scientific (Pittsburgh, PA) and were activated before use.…”

“…In support of such a role are the high levels of CD36 and its expression pattern along the brush border membrane of the proximal intestine, which is typical of proteins implicated in lipid uptake. 6,7 A recent study by Drover et al 17 showed that CD36 knockout (KO) mice did not exhibit reduced intestinal FA uptake, but had impairments in lymph triacylglcyerol (TG) secretion and in clearance of blood chylomicrons. Whether or not CD36 plays a significant role in intestinal cholesterol uptake and transport in TG-rich lipoproteins in vivo remains unknown.…”

From the gut to the peripheral tissues: the multiple effects of butyrate

“…In the GIT, butyrate is naturally present in high concentration in the lumen of the large intestine. It is preferentially taken up by the colonic epithelium where it is actively metabolised to produce energy (3,4) . Much attention has been devoted to the anticancerous properties of butyrate in human nutrition despite numerous papers suggesting its role as a growth factor.…”

Expression of the putative membrane fatty acid transporter (FAT) in taste buds of the circumvallate papillae in rats

“…Previously, wc suggested the participation of receptor protein m the fat-sensory mechanism of intestinal epithelial cells [34.35]. In addition, selective expression of FAT in the brush border of jgjunal epithelial cells suggests lhat FAT participates in sensation or absorption of dietary fat [15]. Thus, we conclude that some dietary lat detecting system similar to that in the intestinal epithelium exists in taste cells, and that FAT participates in the sensory mechanism.…”

“…Poirier et at. [15] showed that FAT in the jejunal mucosa is expressed in the brush border of epithelial cells, and FAT mRNA in the small intestine is increased by a LCFA-rich diet, suggesting the participation of FAT in the sensation or absorption of dietary fat. We considered that if FAT or related proteins are involved in the sensation of dietary fat in the oral cavity, they must be expressed in taste organ.…”