Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.

• Klíčová slova
• Antioxidant enzyme, Catalytic activity, Expression, Glutathione, Metabolic dysfunction-associated steatotic liver disease,
• MeSH
• antioxidancia * metabolismus   MeSH
• játra metabolismus   patologie   MeSH
• lidé MeSH
• oxidační stres účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• ztučnělá játra * metabolismus   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia * MeSH
• reaktivní formy kyslíku MeSH

Metabolic dysfunction-associated steatotic liver disease (MASLD) occurs in subjects with obesity and metabolic syndrome. MASLD may progress from simple steatosis (i.e., hepatic steatosis) to steatohepatitis, characterized by inflammatory changes and liver cell damage, substantially increasing mortality. Lifestyle measures associated with weight loss and/or appropriate diet help reduce liver fat accumulation, thereby potentially limiting progression to steatohepatitis. As for diet, both total energy and macronutrient composition significantly influence the liver's fat content. For example, the type of dietary fatty acids can affect the metabolism of lipids and hence their tissue accumulation, with saturated fatty acids having a greater ability to promote fat storage in the liver than polyunsaturated ones. In particular, polyunsaturated fatty acids of n-3 series (omega-3), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been intensively studied for their antisteatotic effects, both in preclinical animal models of obesity and hepatic steatosis and in overweight/obese patients. Their effects may depend not only on the dose and duration of administration of omega-3, or DHA/EPA ratio, but also on the lipid class used for their supplementation. This review summarizes the available evidence from recent comparative studies using omega-3 supplementation via different lipid classes. Albeit the evidence is mainly limited to preclinical studies, it suggests that phospholipids and possibly wax esters could provide greater efficacy against MASLD compared to traditional chemical forms of omega-3 supplementation (i.e., triacylglycerols, ethyl esters). This cannot be attributed solely to improved EPA and/or DHA bioavailability, but other mechanisms may be involved. Keywords: MASLD • Metabolic dysfunction-associated steatotic liver disease • NAFLD • Non-alcoholic fatty liver disease • n-3 polyunsaturated fatty acids.

• MeSH
• játra * metabolismus   účinky léků   patologie   MeSH
• lidé MeSH
• metabolismus lipidů účinky léků   MeSH
• nealkoholová steatóza jater metabolismus   farmakoterapie   dietoterapie   patologie   MeSH
• obezita metabolismus   farmakoterapie   dietoterapie   patologie   MeSH
• omega-3 mastné kyseliny * aplikace a dávkování   metabolismus   terapeutické užití   MeSH
• potravní doplňky * MeSH
• ztučnělá játra metabolismus   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• omega-3 mastné kyseliny * MeSH

A combination of liver and heart dysfunction worsens the prognosis of human survival. The aim of this study was to investigate whether empagliflozin (a sodium-glucose transporter-2 inhibitor) has beneficial effects not only on cardiac and renal function but also on hepatic function. Adult (6-month-old) male spontaneously hypertensive rats (SHR) were fed a high-fat diet (60% fat) for four months to induce hepatic steatosis and mild heart failure. For the last two months, the rats were treated with empagliflozin (empa, 10 mg.kg-1.day-1 in the drinking water). Renal function and oral glucose tolerance test were analyzed in control (n=8), high-fat diet (SHR+HF, n=10), and empagliflozin-treated (SHR+HF+empa, n=9) SHR throughout the study. Metabolic parameters and echocardiography were evaluated at the end of the experiment. High-fat diet feeding increased body weight and visceral adiposity, liver triglyceride and cholesterol concentrations, and worsened glucose tolerance. Although the high-fat diet did not affect renal function, it significantly worsened cardiac function in a subset of SHR rats. Empagliflozin reduced body weight gain but not visceral fat deposition. It also improved glucose sensitivity and several metabolic parameters (plasma insulin, uric acid, and HDL cholesterol). In the liver, empagliflozin reduced ectopic lipid accumulation, lipoperoxidation, inflammation and pro-inflammatory HETEs, while increasing anti-inflammatory EETs. In addition, empagliflozin improved cardiac function (systolic, diastolic and pumping) independent of blood pressure. The results of our study suggest that hepatoprotection plays a decisive role in the beneficial effects of empagliflozin in preventing the progression of cardiac dysfunction induced by high-fat diet feeding.

• Klíčová slova
• Cardiac function, Kidney function, Liver steatosis, Metabolic parameters, SGLT-2 inhibition,
• MeSH
• benzhydrylové sloučeniny * farmakologie   MeSH
• dieta s vysokým obsahem tuků * škodlivé účinky   MeSH
• glifloziny * farmakologie   MeSH
• glukosidy * farmakologie   MeSH
• hypertenze farmakoterapie   MeSH
• játra * účinky léků   metabolismus   patologie   MeSH
• kardiotonika farmakologie   MeSH
• krevní glukóza metabolismus   účinky léků   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   metabolismus   patologie   MeSH
• ochranné látky farmakologie   MeSH
• potkani inbrední SHR * MeSH
• ztučnělá játra prevence a kontrola   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny * MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny * MeSH
• glukosidy * MeSH
• kardiotonika MeSH
• krevní glukóza MeSH
• ochranné látky MeSH

Fecal microbiota transfer may serve as a therapeutic tool for treating obesity and related disorders but currently, there is no consensus regarding the optimal donor characteristics. We studied how microbiota from vegan donors, who exhibit a low incidence of non-communicable diseases, impact on metabolic effects of an obesogenic diet and the potential role of dietary inulin in mediating these effects. Ex-germ-free animals were colonized with human vegan microbiota and fed a standard or Western-type diet (WD) with or without inulin supplementation. Despite the colonization with vegan microbiota, WD induced excessive weight gain, impaired glucose metabolism, insulin resistance, and liver steatosis. However, supplementation with inulin reversed steatosis and improved glucose homeostasis. In contrast, inulin did not affect WD-induced metabolic changes in non-humanized conventional mice. In vegan microbiota-colonized mice, inulin supplementation resulted in a significant change in gut microbiota composition and its metabolic performance, inducing the shift from proteolytic towards saccharolytic fermentation (decrease of sulfur-containing compounds, increase of SCFA). We found that (i) vegan microbiota alone does not protect against adverse effects of WD; and (ii) supplementation with inulin reversed steatosis and normalized glucose metabolism. This phenomenon is associated with the shift in microbiota composition and accentuation of saccharolytic fermentation at the expense of proteolytic fermentation.

• Klíčová slova
• fecal microbiota transfer, inulin, liver steatosis, proteolytic fermentation, vegan microbiota,
• MeSH
• fekální transplantace MeSH
• glukosa farmakologie   MeSH
• inulin farmakologie   MeSH
• lidé MeSH
• myši MeSH
• potravní vláknina farmakologie   MeSH
• střevní mikroflóra * MeSH
• vegani MeSH
• západní dieta MeSH
• ztučnělá játra * prevence a kontrola   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukosa MeSH
• inulin MeSH
• potravní vláknina MeSH

While fatty liver disease is a well-characterized entity, it is currently getting a completely new image. Its treatment is clearly an interdisciplinary challenge. The number of patients with fatty liver disease will be by no means negligible. The issue of fatty liver disease is not infrequently referred to in association with statin therapy instituted in an effort to treat metabolic syndrome and to reduce cardiovascular risks as part of preventive therapy. The attention focused on the increase in alanin aminotransferase levels during statin therapy is absolutely inadequate. The study includes an overview of the topic showing the induced rise in alanin aminotransferase is merely an accompanying phenomenon, mostly of no clinical relevance. An acceptable increase in alanin aminotransferase should not provide a reason for statin withdrawal in the usual spectrum of patients with metabolic syndrome and fatty liver disease. A distinct advantage is cooperation among a hepatologist, a cardiologist, and a diabetes expert.

• MeSH
• alanintransaminasa metabolismus   MeSH
• HIV infekce komplikace   MeSH
• lidé MeSH
• metabolický syndrom komplikace   farmakoterapie   MeSH
• obezita komplikace   MeSH
• statiny škodlivé účinky   farmakologie   terapeutické užití   MeSH
• ztučnělá játra farmakoterapie   etiologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alanintransaminasa MeSH
• statiny MeSH

We studied the effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activation on serum concentrations and tissue expression of resistin, adiponectin, and adiponectin receptor-1 and -2 (AdipoR1 and AdipoR2) mRNA in normal mice and mice with insulin resistance induced by lipogenic, simple-carbohydrate diet (LD). Sixteen weeks of LD feeding induced obesity with liver steatosis and increased insulin levels but did not significantly affect circulating adiponectin or resistin. Treatment with PPAR-alpha agonist fenofibrate decreased body weight and fat pad weight and ameliorated liver steatosis in LD-fed mice with concomitant reduction in blood glucose, free fatty acid, triglyceride, serum insulin levels, and homeostasis model assessment index values. Euglycemic-hyperinsulinemic clamp demonstrated the development of whole-body and liver insulin resistance in LD-fed mice, which were both normalized by fenofibrate. Fenofibrate treatment markedly increased circulating resistin levels on both diets and adiponectin levels in chow-fed mice only. Fat adiponectin mRNA expression was not affected by fenofibrate treatment. Resistin mRNA expression increased in subcutaneous but not gonadal fat after fenofibrate treatment. In addition to fat, a significant amount of adiponectin mRNA was also expressed in the muscle. This expression markedly increased after fenofibrate treatment in chow- but not in LD-fed mice. Adipose tissue expression of AdipoR1 mRNA was significantly reduced in LD-fed mice and increased after fenofibrate treatment. In conclusion, PPAR-alpha activation ameliorated the development of insulin resistance in LD-fed mice despite a major increase in serum resistin levels. This effect could be partially explained by increased AdipoR1 expression in adipose tissue after fenofibrate treatment.

• MeSH
• adiponektin krev   genetika   MeSH
• dieta MeSH
• dietní sacharidy aplikace a dávkování   MeSH
• exprese genu účinky léků   MeSH
• fenofibrát aplikace a dávkování   MeSH
• glykemický clamp MeSH
• hmotnostní úbytek účinky léků   MeSH
• inzulin krev   farmakologie   MeSH
• inzulinová rezistence * MeSH
• játra chemie   účinky léků   MeSH
• kosterní svaly chemie   MeSH
• krevní glukóza analýza   MeSH
• kyseliny mastné neesterifikované analýza   MeSH
• lipidy biosyntéza   MeSH
• messenger RNA analýza   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita krev   etiologie   patofyziologie   MeSH
• PPAR alfa agonisté   fyziologie   MeSH
• receptory adiponektinu MeSH
• receptory buněčného povrchu genetika   MeSH
• resistin krev   genetika   MeSH
• triglyceridy krev   MeSH
• tuková tkáň chemie   patologie   MeSH
• velikost orgánu účinky léků   MeSH
• ztučnělá játra krev   farmakoterapie   etiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adiponectin receptor 1, mouse MeSH Prohlížeč
• adiponectin receptor 2, mouse MeSH Prohlížeč
• adiponektin MeSH
• dietní sacharidy MeSH
• fenofibrát MeSH
• inzulin MeSH
• krevní glukóza MeSH
• kyseliny mastné neesterifikované MeSH
• lipidy MeSH
• messenger RNA MeSH
• PPAR alfa MeSH
• receptory adiponektinu MeSH
• receptory buněčného povrchu MeSH
• resistin MeSH
• triglyceridy MeSH

BACKGROUND: Steatosis of the liver is the most frequent diffuse liver disease and its detection increased markedly due to ultrasonography. The presence of lipid particles in hepatocytes alters the ultrastructure of cellular membranes. The damaged cell is unable to meet adequately the energy requirements of phospholipid synthesis, the latter being the basic component of cellular and subcellular membranes. Substitution of "essential" phospholipids plays an important role in their regeneration. OBJECTIVE: The objective of the open trial without controls was to obtain preliminary information on the effectiveness of Essentiale forte cps. in the treatment of steatosis of the liver of varying etiology in a group of 30 women, focused on changes in the ultrasonic pictures and a parallel follow-up of laboratory findings and subjective feelings, to be followed subsequently by a placebo controlled double blind trial. METHODS AND RESULTS: Ultrasonic examinations were made using a Hewlett-Packard apparatus (77065AR). The sonographic criterium of steatosis was the finding of a diffusely enhanced echogenicity of the liver parenchyma associated as a rule with varying degrees of hepatomegaly with a smooth rounded margin and readily apparent hepatic veins with a normal lumen. The preparation Essentiale forte, cps. Rhône-Poulenc Rorer Co., contains natural "essential" phospholipids, diglyceride esters of cholinephosphoric acid (enriched with unsaturated fatty acids (linolic, linoleic, oleic) 300 mg, vitamin B1 6 mg, vitamin B2 6 mg, vitamin B6 6 mg, vitamin B12 6 micrograms, nicotinamide 30 mg, vitamin E 6 mg. Six tablets per day (2 x 3 tablets) were administered for six months. The clinical, ultrasonic and laboratory examination were made at the onset of the trial and then after the second and sixth month. From the total number of 28 women who completed treatment in 29 % (8 woman) were free from sonographic signs of steatosis and only in 25 % (7 women) the finding remained unaltered. In the remainder the ultrasonic picture improved only partly, in 10 of 11 women (91 %) the non-homogeneity of the parenchyma disappeared, in 3 of 12 women (25 %) the conduction of acoustic signals improved. The authors recorded also regression of hepatomegaly from 12.9 +/- 1.5 cm to 11.4 +/- 1.0 cm (p < 0.0001). There was also a significant decline of laboratory values: ALT from 1.650 +/- 1.612 mu kat/l to 0.812 +/- 0.392 mu kat/l (p < 0.0014), AST from 1.308 +/- 1.341 mu kat/l to 0.613 +/- 0.206 mu kat/l (p < 0.0038), GMT from 2.525 +/- 3.374 mu kat/l to 0.976 +/- 0.727 mu kat/l (p < 0.0078). A statistically significant decline was also found in mean values of total bilirubin (p < 0.0316), cholesterol (p < 0.0129) and triglycerides (p < 0.001). In all patients subjective sensations improved (p < 0.05). CONCLUSIONS: The authors provided evidence than in 53.6 % of patients the effect of six-month treatment with Essentiale forte was very good (improvement of all investigated parameters), partial in 42.9 % (improvement of laboratory findings and subjective complaints) ad not quite satisfactory in 3.6 % (only improvement of subjective feelings).

• MeSH
• dospělí MeSH
• fosfatidylcholiny terapeutické užití   MeSH
• játra diagnostické zobrazování   MeSH
• lidé MeSH
• mladiství MeSH
• ultrasonografie MeSH
• ztučnělá játra diagnostické zobrazování   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• essential 303 forte MeSH Prohlížeč
• fosfatidylcholiny MeSH

• MeSH
• isoprenalin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• játra patologie   MeSH
• krysa rodu Rattus MeSH
• metabolismus lipidů * MeSH
• ztučnělá játra farmakoterapie   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• isoprenalin MeSH

• MeSH
• hypercholesterolemie farmakoterapie   MeSH
• koronární nemoc farmakoterapie   MeSH
• kyseliny nikotinové terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ztučnělá játra farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyseliny nikotinové MeSH