Rapid upregulation of the basolateral glucose transporter, GLUT2, following short-chain fatty acid administration in rats receiving total parenteral nutrition

The regulation of intestinal function is poorly understood despite a need to increase nutrient uptake in many clinical settings. Total parenteral nutrition results in gastrointestinal mucosat atrophy. TPN-induced atrophy can be reduced with systemic short-chain fatty acid (SCFA) administration, however the effect of these nutrients on mucosal nutrient transport is largely unknown. The purpose of this study was to determine time-dependent effects of SCFAs on glucose transporter abundance using a parenteral nutrition model. Male Sprague Dawley rats (246±2g; n=38) received continuous nutrient infusions for 72h following jugular catheterization as either standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous formulation containing SCFA (TPN+SCFA; 36 mmol/L acetate, 15 mmol/L propionate and 9 mmol/L butyrate). Animals were randomly assigned to 1 of 5 treatments: standard TPN for 72h; TPN+SCFA for 72h, or; standard TPN followed by TPN+SCFA for the final 6, 12 or 24h. Northern blot analysis confirmed that jejunal mRNA abundance of the basolateral glucose transporter, GLUT2, was increased (p=0.0001) in the TPN+SCFA groups at all time points compared to the control TPN group. GLUT2 protein abundance, measured using Western blot analysis, tended to increase (p=0.1) in the jejunum following 6, 12 and 24h of TPN+SCFA, and increased (p<0.05) at these time points in the ileum. Jejunal and ileal mRNA and protein abundance of SGLT-l, the brush border sodium/glucose cotransporter, did not differ among groups. These results suggest that intravenous SCFAs upregulate nutrient uptake independent of luminal stimuli by increasing basolateral nutrient transport. The addition of SCFAs to current TPN formulations may be warranted to improve functional characteristics of the gastrointestinal tract.