2‐Deoxy‐d‐glucose uptake and fatty acid content in fibroblast cultures from children with syndromic paucity of interlobular bile ducts (alagille syndrome)

Abstract

2-Deoxy-D-glucose (2-DOG) uptake was studied in skin fibroblast cultures from control children and children with Alagille syndrome or syndromic paucity of interlobular bile ducts (PILBD). No significant differences in uptake were observed between patients and controls. However, as the scatter of the results was larger in the fibroblasts from patients, we attempted to establish for these patients a relationship between 2-DOG uptake and some biochemical parameters. We observed an inverse relationship between this uptake and the levels of plasma cholesterol and phospholipids (r = -0.85). Compared to controls, 2-DOG uptake was significantly lower in cultures from patients who had very high levels of cholesterol (P2 group), but not in cultures from patients with moderately increased levels of cholesterol (P1 group). The level of total cellular cholesterol in cultured cells from the P1 and P2 groups was not significantly different from the control level, but we found marked differences between the concentrations of fatty acids. In the cultures from patients (especially the P2 group), we observed a significant increase in total fatty acids; among the saturated fatty acids, this increase chiefly concerned the 18:0 (14%) and among the polyunsaturated the n - 3 fatty acids (55%). The high concentrations of 20:5, 22:5 and 22:6, which enhance membrane fluidity, might explain the decrease in 2-DOG uptake found in the cultures from patients (P2 group) with PILBD. The nature of these abnormalities might be connected with the genetic origin of Alagille syndrome.

Fatty acid content in lymphocytes from children with syndromic paucity of interlobular bile ducts, Alagille syndrome

“…The increase in n-3 FA induces strong modifications in membrane structure and contributes to changes in membrane fluidity (Spector 1989). These results are consistent with our previously published results concerning fibroblast cultures from PILBD patients who displayed a decrease in 2-deoxy-o-glucose uptake and an increase in n-3 FA in comparison with control fibroblasts (Couturier and Lemonnier 1991).…”

“…The goal of this work was a comparison of the lymphocyte fatty acid concentrations obtained from control children and patients with PILBD. This was investigated under two experimental conditions, either immediately after separation of the mononuclear cells or after short-term culture, to demonstrate whether the particular fatty acid changes found previously in fibroblast cultures from these patients (Couturier and Lemonnier 1991) were also present in other tissues such as lymphocytes.…”

“…However, no defect in the LDL receptor has been detected (Kadhom et al, unpublished). Further work from this laboratory showed a decrease in 2-deoxy-D-glucose uptake and a significant increase in polyunsaturated fatty acids of the n-3 series in patient fibroblast phospholipids compared to the controls (Couturier and Lemonnier 1991). The fact that this significant n-3 fatty acid increase was observed after several cell culture passages raised the possibility that these changes might be due to some constitutive defect related to the genetic anomaly.…”