Background and aims: The increased lipid peroxJdation demonstrated in NASH might be related either to higher circulating levels of pro-oxidants and/or to a peculiar vulnerability of plasma lipids to oxidative stress. Insulin resistance, a common feature in NASI-I, has been associated with increased oxidative stress. The aims of our study were to establish whether the susceptibility of LDL-cholesternl particles to oxidation is increased in NASH patients and whether this could be related to insulin resistance. Methods: We studied 11 non-obese, non diabetic patients with NASH (BM1=26.6 _+ 1.6), and 5 matched controls. The following parameters were evaluated: 1) plasma lipid profile 2) total body lipid oxidation by indirect calorimetry 3) plasma LDL-cholesterol vulnerability to oxidation as assessed by the lenght of the lag-phase during copper-catalyzed LDL oxidative modifications; 4) insulin sensitivity by hyperinsulinemic (1 mU/Kg min) euglycemic clamp. Results: The basal lag-phase was significantly shorter in NASH patients compared to controls (49 +_ 11 vs 68 _+ 10 rain, respectively; p-O.01). Plasma lipid profile was comparable in the two groups, with the exception of a slightly higher triglycerides concentration in NASH (117 _+ 49 vs 71 _+ 11 mg/dL; p=O.05). A slight inverse correlation was found between plasma triglycerides and lag phase (r= - 0.43) and FFA concentrations and lag phase (r= -0.52) in NASH patients but not in controls. Total lipid oxidation was 1.13 _+ 0,25 and 1.00 _+ 0.21 i~mol/kg min in NASH and controls, respectively (p = ns) and inversely correlated with the lag-phase in both groups (r= -0.58 and -0.46). ~nsulin sensitivity was definitely reduced in NASH patients compared to controls (glucose infusion rate = 4.49 _+ 1.48 vs 7.67 _+ 0.54 mg/kg min; p<O.O01). The lag-phase did not change after the euglycemic hyperinsulinemic clamp in both groups (p=ns) and did not correlate with insulin sensitivity. Conclusions: The increased susceptibility of LDLcholesterol particles contributes to enhanced lipid peroxidation in patients with NASH, independently from lipid levels and lipid oxidation. The LDL oxidability is not affected by insulin administration and does not appear to be related to insulin resistance.
Increased LDL-cholesterol susceptibility to oxidation contributes to oxidative damage in non alcoholic steatohepatitis (NASH).
VANNI, Ester;BUGIANESI, Elisabetta;GAMBINO, Roberto;CASSADER, Maurizio;RIZZETTO, Mario
2002-01-01
Abstract
Background and aims: The increased lipid peroxJdation demonstrated in NASH might be related either to higher circulating levels of pro-oxidants and/or to a peculiar vulnerability of plasma lipids to oxidative stress. Insulin resistance, a common feature in NASI-I, has been associated with increased oxidative stress. The aims of our study were to establish whether the susceptibility of LDL-cholesternl particles to oxidation is increased in NASH patients and whether this could be related to insulin resistance. Methods: We studied 11 non-obese, non diabetic patients with NASH (BM1=26.6 _+ 1.6), and 5 matched controls. The following parameters were evaluated: 1) plasma lipid profile 2) total body lipid oxidation by indirect calorimetry 3) plasma LDL-cholesterol vulnerability to oxidation as assessed by the lenght of the lag-phase during copper-catalyzed LDL oxidative modifications; 4) insulin sensitivity by hyperinsulinemic (1 mU/Kg min) euglycemic clamp. Results: The basal lag-phase was significantly shorter in NASH patients compared to controls (49 +_ 11 vs 68 _+ 10 rain, respectively; p-O.01). Plasma lipid profile was comparable in the two groups, with the exception of a slightly higher triglycerides concentration in NASH (117 _+ 49 vs 71 _+ 11 mg/dL; p=O.05). A slight inverse correlation was found between plasma triglycerides and lag phase (r= - 0.43) and FFA concentrations and lag phase (r= -0.52) in NASH patients but not in controls. Total lipid oxidation was 1.13 _+ 0,25 and 1.00 _+ 0.21 i~mol/kg min in NASH and controls, respectively (p = ns) and inversely correlated with the lag-phase in both groups (r= -0.58 and -0.46). ~nsulin sensitivity was definitely reduced in NASH patients compared to controls (glucose infusion rate = 4.49 _+ 1.48 vs 7.67 _+ 0.54 mg/kg min; p
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