The Effects of alpha-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine-Choline Deficient Diet-Induced NAFLD

Development of nonalcoholic fatty liver disease (NAFLD) occurs through initial steatosis and subsequent oxidative stress. The aim of this study was to examine the effects of -lipoic acid (LA) on methionine-choline deficient (MCD) diet-induced NAFLD in mice. Male C57BL/6 mice (n=21) were divided into three groups (n=7 per group): (1) control fed with standard chow, (2) MCD2 groupfed with MCD diet for 2 weeks, and (3) MCD2+LA group2 weeks on MCD receiving LA i.p. 100mg/kg/day. After the treatment, liver samples were taken for pathohistology, oxidative stress parameters, antioxidative enzymes, and liver free fatty acid (FFA) composition. Mild microvesicular hepatic steatosis was found in MCD2 group, while it was reduced to single fat droplets evident in MCD2+LA group. Lipid peroxidation and nitrosative stress were increased by MCD diet, while LA administration induced a decrease in liver malondialdehyde and nitrates+nitrites level. Similary, LA improved liver antioxidative capacity by increasing total superoxide dismutase (tSOD), manganese SOD (MnSOD), and copper/zinc-SOD (Cu/ZnSOD) activity as well as glutathione (GSH) content. Liver FFA profile has shown a significant decrease in saturated acids, arachidonic, and docosahexaenoic acid (DHA), while LA treatment increased their proportions. It can be concluded that LA ameliorates lipid peroxidation and nitrosative stress in MCD diet-induced hepatic steatosis through an increase in SOD activity and GSH level. In addition, LA increases the proportion of palmitic, stearic, arachidonic, and DHA in the fatty liver. An increase in DHA may be a potential mechanism of anti-inflammatory and antioxidant effects of LA in MCD diet-induced NAFLD

The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease

We used rimonabant to investigate the role of CB1 receptor on hepatic FFAs profile during NAFLD. Male mice C57BL/6 were divided into: control group fed with control diet 20 weeks (C; n = 6); group fed with HFD 20 weeks (HF; n = 6); group fed with control diet and treated with rimonabant after 18 weeks (R; n = 9); group fed with HFD and treated with rimonabant after 18 weeks (HFR; n = 10). Rimonabant (10 mg/kg) was administered daily to HFR and R group by oral gavage. Rimonabant decreased liver palmitic acid proportion in HFR group compared to HF group (p  lt  0.05). Liver stearic and oleic acid proportions were decreased in R group compared to control (p  lt  0.01 respectively). Rimonabant increased liver linoleic and arachidonic acid proportions in HFR group compared to HF group (p  lt  0.01 respectively). CB1 blockade may be useful in the treatment of HFD-induced NAFLD due to modulation of plasma lipid and hepatic FFA profile

Time-dependent Changes and Association Between Liver Free Fatty Acids, Serum Lipid Profile and Histological Features in Mice Model of Nonalcoholic Fatty Liver Disease

Background and Aims. Methionine-choline deficient (MCD) diet duration necessary for development of non-alcoholic fatty liver disease (NAFLD) and the dynamic of lipid profile and fatty acids are not completely established. The study examined dynamics and association between liver free fatty acids (FFA), serum lipid profile and liver morphological changes on MCD diet-induced NAFLD in mice. Methods. Male C57BL/6 mice (n = 28) were divided into four groups (n = 7 per group): control: fed with standard chow, MCD diet-fed groups: 2, 4 or 6 weeks. After treatment, liver and blood samples were taken for histopathology, serum lipid profile, and liver FFA composition. Results. Hepatic FFA profile showed a decrease in saturated acids, arachidonic and docosahexaenoic acid, whereas proportions of docosapentaenoic, oleic and linoleic acid were increased. Total cholesterol, HDL and triglycerides progressively decreased, whereas LDL level progressively increased. Focal fatty change in the liver appeared after 2 weeks, whereas diffuse fatty change with severe inflammation and ballooned hepatocytes were evident after 6 weeks. Conclusions. Six-week diet model may be appropriate for investigation of the role of lipotoxicity in the progression of NAFLD. Therefore, supplementation with n-3 polyunsaturated acid like DHA, rather than DPA, especially in the initial stage of fatty liver disease, may potentially have preventive effects and alleviate development of NAFLD/NASH and may also potentially reduce cardiovascular risk by moderating dyslipidemia

Myocardial Na+ K+-ATPase and SERCA: Clinical and Pathological Significance From a Cytological Perspective

Structure and functions of Na+/K+-ATPase and SERCA are described with details on their subunits, isoforms, and intracellular localization. Main regulatory mechanisms are summarized. Molecular mechanisms of cell death and heart failure are explained with the analysis of the role of Na+/K+-ATPase and SERCA in these processes. Facts are considered from a cytological, pathological, and clinical perspective with an accent to new therapeutic strategies. The aim of this contribution is an overview of functional results in a structural context.Part of the Advances in Biochemistry in Health and Disease book series (ABHD,volume 15)