The physiological significance of the presence of GLUT2 at the food‐facing pole of intestinal cells is addressed by a study of fructose absorption in GLUT2‐null and control mice submitted to different sugar diets. Confocal microscopy localization, protein and mRNA abundance, as well as tissue and membrane vesicle uptakes of fructose were assayed. GLUT2 was located in the basolateral membrane of mice fed a meal devoid of sugar or containing complex carbohydrates. In addition, the ingestion of a simple sugar meal promoted the massive recruitment of GLUT2 to the food‐facing membrane. Fructose uptake in brush‐border membrane vesicles from GLUT2‐null mice was half that of wild‐type mice and was similar to the cytochalasin B‐insensitive component, i.e. GLUT5‐mediated uptake. A 5 day consumption of sugar‐rich diets increased fructose uptake fivefold in wild‐type tissue rings when it only doubled in GLUT2‐null tissue. GLUT5 was estimated to contribute to 100 % of total uptake in wild‐type mice fed low‐sugar diets, falling to 60 and 40 % with glucose and fructose diets respectively; the complement was ensured by GLUT2 activity. The results indicate that basal sugar uptake is mediated by the resident food‐facing SGLT1 and GLUT5 transporters, whose mRNA abundances double in long‐term dietary adaptation. We also observe that a large improvement of intestinal absorption is promoted by the transient recruitment of food‐facing GLUT2, induced by the ingestion of a simple‐sugar meal. Thus, GLUT2 and GLUT5 could exert complementary roles in adapting the absorption capacity of the intestine to occasional or repeated loads of dietary sugars.

CYP2E1 is involved in the activation of various carcinogens, including N-nitrosamines, which are believed to be important in human carcinogenesis. Humans exhibit wide interindividual variability in levels of CYP2E1 mRNA and protein, which might explain interindividual differences in susceptibility to carcinogens activated by CYP2E1. Such variability could be due either to genetic polymorphisms observed in the CYP2E1 gene (Rsa I in the 5 '-flanking region, Dra I in intron 6 and Taq I in intron 7) or to varying inducibility by xenobiotics. The aim of the present study was to establish whether, in a Caucasian population (n=93), there existed a relationship between allelic forms of the CYP2E1 gene and the phenotype determined in vitro by hepatic ability to 6-hydroxylate chlorzoxazone. Rates of chlorzoxazone- 6-hydroxylation were significantly correlated with levels of immunochemically measured CYP2E1 (p<0.001). CYP1A2,2C8,2C9,2C18,2D6,3A4 and 3A5 did not appear to be significantly involved in chlorzoxazone metabolism, whereas the participation of CYP1A1 could not be excluded. Frequencies of the rare alleles for the three polymorphism sites were 2.2% for Rsa 1,7.5% for Dra I and 8.5% for Taq I. Despite substantial interindividual variations in chlorzoxazone hydroxylase activity, no relationship between any of the three polymorphisms and CYP2E1 activity was established. Therefore, in humans, interindividual variability in CYP2E1 levels is probably due to differing induction levels as a result of environmental factors, or to genetic factors other than those studied in this work.

Enterocytes, the intestinal absorptive cells, have to deal with massive alimentary lipids upon food consumption. They orchestrate complex lipid-trafficking events that lead to the secretion of triglyceride-rich lipoproteins and/or the intracellular transient storage of lipids as lipid droplets (LDs). LDs originate from the endoplasmic reticulum (ER) membrane and are mainly composed of a triglyceride (TG) and cholesterol-ester core surrounded by a phospholipid and cholesterol monolayer and specific coat proteins. The pivotal role of LDs in cellular lipid homeostasis is clearly established, but processes regulating LD dynamics in enterocytes are poorly understood. Here we show that delivery of alimentary lipid micelles to polarized human enterocytes induces an immediate autophagic response, accompanied by phosphatidylinositol-3-phosphate appearance at the ER membrane. We observe a specific and rapid capture of newly synthesized LD at the ER membrane by nascent autophagosomal structures. By combining pharmacological and genetic approaches, we demonstrate that autophagy is a key player in TG targeting to lysosomes. Our results highlight the yet-unraveled role of autophagy in the regulation of TG distribution, trafficking, and turnover in human enterocytes.