Basolateral presence of the proinflammatory cytokine tumor necrosis factor -α and secretions from adipocytes and macrophages reduce intestinal sugar transport

We have previously demonstrated in Caco-2 cells that tumor necrosis factor- (TNF-) inhibits sugar uptake, acting from the apical membrane, by decreasing the expression of the Na+-glucose cotransporter SGLT1 in the brush border membrane. The goal was to investigate the hypothesis that TNF- from abdominal adipose tissue (adipocytes and macrophages) would decrease sugar and amino acid transport acting from the basolateral membrane of the enterocytes. TNF- placed in the basal compartment of Caco-2 cells decreased -methyl- d-glucose (MG) and glutamine uptake. The apical medium derived from these Caco-2 cells apically placed in another set of cells, also reduced sugar and glutamine transport. Reverse-transcription polymerase chain reaction analysis demonstrated upregulation of TNF-, IL-1, and MCP1 expression in Caco-2 cells exposed to basal TNF-. Similarly, MG uptake was inhibited after Caco-2 cells were incubated, in the basal compartment, with medium from visceral human mesenchymal stem cells-derived adipocytes of overweight individuals. The apical medium collected from those Caco-2 cells, and placed in the upper side of other set of cells, also decreased sugar uptake. Basal presence of medium derived from lipopolysaccharide-activated macrophages and nonactivated macrophages decreased MG uptake as well. Diet-induced obese mice showed an increase in the visceral adipose tissue surrounding the intestine. In this physiological condition, there was a reduction on MG uptake in jejunal everted rings. Altogether, these results suggest that basolateral TNF-, which can be produced by adipocytes and macrophages during obesity, would be able to activate TNF- and other proinflammatory proteins expression in the small intestine and diminish intestinal sugar and amino acids transport.