Maud Lemoine

Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease.

Aims: The aim of this study was to determine whether serum levels of adipokines, including the ratio of serum adiponectin to leptin (A/L) levels could predict the severity of liver injury in patients with non‐alcoholic fatty liver disease (NAFLD).

Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: A meta-analysis

BACKGROUND & AIMS Recent studies suggested that SVR rates might be lower in HCV patients with insulin resistance (IR) than in patients without IR, but the extent of the impact of IR on treatment response has not been established. We aimed to confirm the role of IR assessed by the homoeostasis model assessment (HOMA-IR) on SVR and to determine its magnitude. METHODS We performed meta-analysis of studies evaluating the impact of IR in HCV patients treated with pegylated interferon and ribavirin. RESULTS Fourteen studies involving 2732 patients were included. SVR was less frequent in patients with IR than in patients without IR (mean difference: -19.6%, 95% CI: -29.9% to -9.4%, p<0.001). In sensitivity analyses according to HCV-1 patients, patients with IR also less frequently attained a SVR than patients without IR (mean difference: -13.0%, 95% CI: -22.6% to -3.4%, p=0.008). In addition, the baseline HOMA-IR index was lower in responders than in non-responders (mean difference: -0.92, 95% CI: -1.53 to -0.32, p<0.001). In sensitivity analyses restricted to HCV-1 patients, the baseline HOMA-IR index remained lower in responders than in non-responders (mean difference: -0.63, 95% CI: -1.13 to -0.14, p<0.001). CONCLUSIONS HCV patients with IR have a 20% lower SVR than patients without IR. The baseline HOMA-IR index is a major determinant of SVR.

Physical state of κ-carrageenan modulates the mode of action of κ-carrageenase from Pseudoalteromonas carrageenovora

Pseudoalteromonas carrageenovora kappa-carrageenase is a glycoside hydrolase involved in the bioconversion of carrageenans. Carrageenans are sulfated galactans that are densely packed in red algal cell walls. Previous crystallographic investigations revealed that the active site of kappa-carrageenase has a tunnel-shaped topology, suggesting a processive mode of action for this enzyme. To biochemically characterize the enzymatic depolymerization of kappa-carrageenan, soluble and solid substrates (in both gel and powder forms) were incubated with P. carrageenovora kappa-carrageenase. The average molecular mass of soluble carrageenan decreased rapidly, and all possible degradation products were observed, suggesting random degradation of kappa-carrageenan. In contrast, as expected for a processive-type carrageenase, the average molecular mass of solid carrageenan decreased very slowly, and tetrasaccharide production was high. Interestingly, experimentally determined processivity was similar for gel and powder, suggesting that, in addition to an adapted catalytic site, the substrate must be in the solid state for kappa-carrageenase processivity to operate, whatever the level of carrageenan ordering.

Enzymatic degradation of κ-carrageenan in aqueous solution.

Enzymatic degradation of standard κ-carrageenan and the low-gelling hybrid κ-/μ-carrageenan were conducted using recombinant Pseudoalteromonas carrageenovora κ-carrageenase. The initial velocity of the enzyme was determined as a function of varying Tris or NaI concentrations and at constant 200 mM cosolutes concentration, adjusting NaI and Tris concentrations accordingly. In both cases, we observed strong inhibition of the enzyme with increasing amounts of iodide. The characterization of the κ- and κ-/μ-carrageenan ordering by optical rotation and the visualization of iodide binding on carrageenan by (127)I NMR revealed that inhibition was not caused by the disordered-ordered transition of carrageenan in NaI, but by iodide binding. These results were confirmed by analysis of the degradation products by gel permeation chromatography. Degradation of carrageenan in the disordered state led to a rapid decrease in molecular mass and the production of all possible neo-κ-carrabiose oligomers. In the ordered conformation, the degradation kinetics, the decrease of average molecular weight, and the chain population distribution of degradation products varied with iodide concentration. These observations were interpreted to be the result of increasing amounts of bound iodide on carrageenan helices that, in turn, impede enzyme catalysis. Based on these results, we propose a single-helix ordered conformation state for κ-carrageenan and reject the previously advocated double-helix model.