Perturbations of glucose metabolism associated with HIV infection in human intestinal epithelial cells: A multinuclear magnetic resonance spectroscopy study

Objective: To analyse the effect of HIV-1 infection on the glucose metabolism of human intestinal epithelial cells. Methods: HT-29 cells were infected with HIV-1(NDK) and studied 3 weeks (acutely infected cells) or 9 months (chronically infected cells) post-infection. Perchloric acid extracts were analysed by high-resolution H-1, P-31 and C-13 nuclear magnetic resonance spectroscopy. Metabolite concentrations and specific C-13 enrichments were quantified for chronically infected, acutely infected and control cells grown in Dulbecco's modified Eagle's medium containing natural-abundance or l-C-13-enriched glucose to determine significant differences between infected and non-infected cells. Results: Chronically HIV-infected cells showed alterations in glycerol-3-phosphate (+40%), fructose-l,6-diphosphate (-66%), uridine diphosphate glucuronic acid (-33%), lactate (+75%) and [l-(13)Clglucose (+181%) levels, and in specific lactate 3-C-13 enrichment (+19%) when compared with controls. Acutely infected cells exhibited decreased fructose-l,6-diphosphate (-58%) and increased nicotinamide adenine dinucleotide (+33%) levels relative to controls. Conclusion: HIV-1 infection results in a disturbance of glycolytic and oxidative activities in human intestinal epithelial cells. This finding supports the concept that HIV-1 may directly impair some metabolic functions of the intestinal epithelium, and that it can be considered a potential aetiological agent for HIV-associated enteropathy.