Moderate Alcohol Consumption Inhibits Sodium-Dependent Glutamine Co-Transport in Rat Intestinal Epithelial Cells in Vitro and Ex Vivo

Abstract

Malnutrition is present in chronic alcoholics. However, how moderate alcohol consumption affects the absorption of nutrients like glutamine has not been investigated. Glutamine, an amino acid, is vital to gastrointestinal health. Glutamine is absorbed via sodium-dependent glutamine co-transport (B0AT1; SLC6A19) along the brush border membrane of absorptive villus cells. Rat intestinal epithelial cells (IEC-18) and sixteen-week-old Sprague Dawley rats were administered the equivalent of a 0.04% blood alcohol content of ethanol (8.64 mM; 2 g/kg) to investigate the effect of moderate alcohol on sodium-glutamine co-transport. Sodium-dependent 3H-glutamine uptakes were performed to measure B0AT1 activity. Inorganic phosphate was measured as a function of Na-K-ATPase activity. Protein expression was analyzed by immunohistochemical and Western blot analysis. Ethanol significantly inhibited sodium-dependent glutamine absorption and Na-K-ATPase activity in enterocytes in vitro and ex vivo. Kinetic studies suggested that the mechanism of inhibition was due to decreased maximal rate of uptake (Vmax) of the B0AT1 co-transporter, corresponding to decreased B0AT1 protein expression and secondary to an inhibited sodium-gradient at the cellular level in vitro and ex vivo. In all, moderate ethanol significantly inhibited glutamine absorption at the level of decreased B0AT1 expression at the brush border membrane and a reduced sodium gradient, which may contribute to malnutrition present in chronic alcoholics.

Impaired Glycolysis Promotes Alcohol Exposure-Induced Apoptosis in HEI-OC1 Cells via Inhibition of EGFR Signaling

“…To investigate whether the impaired glycolysis by alcohol exposure could promote cytotoxicity in HEI-OC1 cells, we first analyzed the morphological changes using 3D analyzer in HEI-OC1 cells. Moderate alcohol exposure, defined as the amount in two alcoholic beverages per day for men and one for women, equivalent to a blood alcohol content (BAC) of 0.04%, inhibited the function of intestinal epithelial cells [37]. Since it is not clear to determine the level of inner ear alcohol content by alcohol exposure in BAC of alcohol content, we used two concentrations of alcohol exposure with 0.01% (low) and 0.05% (high) in our system as low inner ear alcohol content and high inner ear alcohol content.…”

Metabolic Abnormalities Linked to Auditory Pathways in ApoE-Knockout HEI-OC1 Cells: A Transcription-Metabolism Co-Analysis

“…Thus, the increased need for glutamine is met by transporter proteins in the cell membrane [ 13 ]. The sodium-dependent neutral amino acid transporter encoded by Slc6a19 causes reduced glutamine uptake after inhibition [ 14 , 15 ] while the L-type amino acid transporter protein 2 (LAT2) encoded by the Slc7a8 gene is responsible for the transport of neutral amino acids, including glutamine: the levels of both of these proteins are reduced in KO cells. It has been shown that the overexpressed Slc7a8 gene can regulate glutamine-dependent mTOR (mammalian target of rapamycin, member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases) activation in cancer, which also requires high glutamine consumption, suggesting its role in glutamine transport [ 16 ].…”

The Influence of Alcohol Consumption on Intestinal Nutrient Absorption: A Comprehensive Review

“…A single standard alcoholic beverage per day for females and two for males, defined as moderate alcohol consumption, is a rational measure of ethanol to investigate [ 27 , 28 ]. Recent studies have shown that even smaller dosages of ethanol can have significant effects on human physiology [ 1 ], nutrient absorption, and can even affect nutrient transporters along the small intestine [ 32 , 33 ].…”

“…Ethanol’s impact on the BBM vitamin B1 transporter was further studied, which kindled interests in investigating the effects of alcohol consumption on intestinal nutrient absorption [ 11 ]. Various studies on the effects of alcohol consumption on the absorption of macronutrients, including water [ 15 , 17 ], carbohydrates, such as glucose [ 7 , 10 , 14 , 17 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ] and xylose, lipids [ 18 , 75 , 76 , 77 , 78 , 79 ], peptides [ 78 , 79 ], and amino acids, such as glutamine [ 33 ], leucine [ 72 , 80 , 81 , 82 ], and glycine, [ 70 ] have been reported ( Table 1 ). Furthermore, alcohol consumption affects the absorption of micronutrients, including water-soluble vitamins, such as vitamin B1 [ 11 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ], B2 [ 90 ], B6 [ 1 ]), B9 [ 8 , 16 , 91 , 92 , 93 , 94 ], B12 […”