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Meldonium-induced steatosis is associated with increased delta 6 desaturation and reduced elongation of n-6 polyunsaturated fatty acids

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Liver Research 2024年第3期8卷 152-164页

作者： Bodil Bjørndal Siri Lunde Tungland Pavol Bohov magne osydnes Simon N.Dankel Lise Madsen Rolf K Berge Department of Clinical Science University of BergenBergenNorway Department of Sports Physical Activity and FoodWestern Norway University of Applied SciencesBergenNorway Department of Chemistry Bioscience and Environmental EngineeringUniversity of StavangerStavangerNorway Department of Clinical Medicine University of BergenBergenNorway Department of Heart Disease Haukeland University HospitalBergenNorway

Background and objective Metabolic associated fatty liver disease(MAFLD)is associated with abnormal lipid *** dysfunction is considered an important factor in the onset of MAFLD,whereas altered fatty acid composition has been linked to the severity of the *** acid(TTA),shown to induce mitochondrial proliferation and alter the fatty acid composition,was used to delay the accumulation of hepatic *** study aimed to evaluate how impaired mitochondrial fatty acid beta-oxidation affects fatty acid composition by incorporating meldonium into a high-carbohydrate *** C57BL/6 mice(n=40)were fed high-carbohydrate diets supplemented with meldonium,TTA,or a combination of meldonium and TTA for 21 *** levels were determined in liver samples,and fatty acid composition was measured in both liver and plasma ***,desaturase and elongase activities were *** hepatic activities and gene expression levels of enzymes involved in fatty acid metabolism were measured in liver samples,whereas carnitines,their precursors,and acylcarnitines were measured in plasma *** The meldonium-induced depletion of L-carnitine and mitochondrial fatty acid oxidation was confirmed by reduced plasma levels of L-carnitine and *** component analyses of the hepatic fatty acid composition revealed clustering dependent on meldonium and *** meldonium-induced increase in hepatic triacylglycerol levels correlated negatively with estimated activities of elongases and was associated with higher estimated activities of delta-6 desaturase(D6D;C18:4n-3/C18:3n-3 and C18:3n-6/C18:2n-6),and increased circulating levels of C18:4n-3 and C18:3n-6(gamma-linolenic acid).TTA mitigated meldonium-induced triacylglycerol levels by 80%and attenuated the estimated D6D activities,and elongation of n-6 polyunsaturated fatty acids(PUFAs).TTA also attenuated the meldonium-mediated reduction of C24:1n-

关键词： Steatosis Fatty acid composition Fatty acid oxidation Meldonium Desaturase Elongasen-6 polyunsaturated fatty acid

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