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5 . 2014

Isomeric specific analysis of hydroxyeicosatetraenoic acid in blood samples from obese patients with non-alcoholic and alcoholic steatohepatitis

Abstract

The aim of the study was to perform isomeric analysis of hydroxyeicosatetraenoic acid (HETE) in blood samples from obese patients with non-alcoholic (NASH) and alcoholic (ASH) steatohepatitis. Sixty nine obese patients with liver steatosis according to abdominal US data and chronic ALT elevation were assign into two groups according to the evaluation of alcohol consumption by GAGE and AUDIT questionnaires: NASH – 39 patients and ASH – 30 patients. The identification and quantification of 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 15-HETE and also non-enzymatic oxidation product 11-HETE in blood plasma were carried out by HPLC-MS-TOF with using 2-hydroxyoctanoic acid as internal standard. The position of hydroxyl group in HETE was elucidated by HPLC-MS/MS. The MS/MS transitions were for 15-HETE m/z 319 → m/z 219; for 11-HETE m/z 319 → m/z 167; for 5-HETE m/z 319 → m/z 115. Patients’ body composition was evaluated by bioelectrical impedance, resting energy expenditures (REE) were assessed by indirect calorimetry and nutrition pattern was examined by food frequency questionnaire. Mean age, BMI and ALT serum level were similar in patients from ASH and NASH groups. Blood plasma 8+12-HETE concentration was also similar in both groups of patients, but concentration of 15-HETE (21,6Ѓ}20,2 vs 11,9Ѓ}13,7 μg/ml, р=0,02) and 11-HETE (20,8Ѓ}21,3 vs 11,2Ѓ}12,9 μg/ml, р=0,03) was significantly higher in NASH patients. ASH patients demonstrated higher lean body mass (68,1Ѓ}10,6 vs 57,9Ѓ}9,8 kg, p<0,001) and muscle mass (39,3Ѓ}6,1 vs 33,2Ѓ}6,8 kg, p<0,04) and higher rate of protein oxidation (98,5Ѓ}31 vs 76,2Ѓ}21,1 g/day, р=0,02) recalculated from REE. There were no differences found in blood lipids content as well as in consumption of total dietary fat, however, there was a trend to difference in saturated/unsaturated fatty acids ratio between groups (2,3Ѓ}0,2 in NASH and 1,4Ѓ}0,3 in ASH patients). In conclusion, the rate of production of eicosatetraenoic acid metabolites by lipoxygenase pathway is different in NASH and ASH overweight patients.

It means that possibly different mechanisms are responsible for formation of potentially toxic fatty acids metabolites in these two types of patients. It seems likely that differences in fatty acids consumption pattern are related to this metabolic pathway.

Keywords:non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic steatohepatitis, obesity, arachidonic acid, 5(S)-hydroxyeicosatetraenoic acid

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CHIEF EDITOR
CHIEF EDITOR
Viktor A. Tutelyan
Full Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety (Moscow, Russia)

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