Liver sinusoidal endothelial cells (LSECs) play a crucial role in regulating the hepatic function. Endoglin (ENG), a transmembrane glycoprotein, was shown to be related to the development of endothelial dysfunction. In this study, we hypothesized the relationship between changes in ENG expression and markers of liver sinusoidal endothelial dysfunction (LSED) during liver impairment. Male C57BL/6J mice aged 9-12 weeks were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet (intrahepatic cholestasis) or choline-deficient l-amino acid defined high-fat diet (CDAA-HFD) (non-alcoholic steatohepatitis (NASH)). Significant increases in liver enzymes, fibrosis, and inflammation biomarkers were observed in both cholestasis and NASH. Decreased p-eNOS/eNOS and VE-cadherin protein expression and a significant increase in VCAM-1 and ICAM-1 expression were detected, indicating LSED in both mouse models of liver damage. A significant reduction of ENG in the DDC-fed mice, while a significant increase of ENG in the CDAA-HFD group was observed. Both DDC and CDAA-HFD-fed mice showed a significant increase in MMP-14 protein expression, which is related to significantly increased levels of soluble endoglin (sENG) in the plasma. In conclusion, we demonstrated that intrahepatic cholestasis and NASH result in an altered ENG expression, predominantly in LSECs, suggesting a critical role of ENG expression for the proper function of liver sinusoids. Both pathologies resulted in elevated sENG levels, cleaved by MMP-14 expressed predominantly from LSECs, indicating sENG as a liver injury biomarker.
- MeSH
- acetamidy * MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- endoglin metabolismus MeSH
- endoteliální buňky metabolismus MeSH
- intrahepatální cholestáza * MeSH
- matrixová metaloproteinasa 14 MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nealkoholová steatóza jater * patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH. METHODS: We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers. Patients underwent laboratory assessment and liver biopsy for metabolic dysfunction-associated steatotic liver disease. Based on 12 lipids, body mass index, aspartate aminotransferase, and alanine aminotransferase, the MASEF score was developed to identify at-risk MASH and compared to the FibroScan-AST (FAST) score. We further compared the performance of a FIB-4 + MASEF algorithm to that of FIB-4 + liver stiffness measurements (LSM) by vibration-controlled transient elastography (VCTE). RESULTS: The diagnostic performance of the MASEF score showed an area under the receiver-operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.76 (95% CI 0.72-0.79), 0.69, 0.74, 0.53, and 0.85 in the derivation cohort, and 0.79 (95% CI 0.75-0.83), 0.78, 0.65, 0.48, and 0.88 in the validation cohort, while FibroScan-AST performance in the validation cohort was 0.74 (95% CI 0.68-0.79; p = 0.064), 0.58, 0.79, 0.67, and 0.73, respectively. FIB-4+MASEF showed similar overall performance compared with FIB-4 + LSM by VCTE ( p = 0.69) to identify at-risk MASH. CONCLUSION: MASEF is a promising diagnostic tool for the assessment of at-risk MASH. It could be used alternatively to LSM by VCTE in the algorithm that is currently recommended by several guidance publications.
Transplantace jater je více než 40 let považována za standardní léčebnou metodu pacientů s život ohrožujícím jaterním onemocněním. V počátečním období byla indikována především u pacientů s jasně infaustní prognózou. Delší přežívání příjemců díky zlepšení chirurgické techniky, intenzivní péče a imunosuprese vedlo k cílení na nemocné s perspektivou dlouhodobého přežití, tedy k odklonu od onkologických indikací k pacientům s cirhózami. Narůstající nepoměr mezi potřebou transplantace a počtem dárcovských orgánů přinesl nutnost přísnějšího výběru, do kterého krom ryze medicinských úvah přicházejí i etické otázky ohledně rovného přístupu k transplantaci a nutnosti docílit s omezenými zdroji co největší transplantační benefit pro co nejširší okruh příjemců. Do vývoje indikací zasáhly jak změny v epidemiologii jaterních nemocí, tak i pokroky v jejich léčbě. Došlo k významnému poklesu zastoupení dříve dominantní virové hepatitidy C. Celosvětově pak narůstá počet pacientů transplantovaných pro nealkoholovou steatohepatitidu i alkoholovou jaterní cirhózu. Velký vývoj byl v poslední dekádě zaznamenán v oblasti nádorových onemocnění jater, především u indikací hepatocelulárního karcinomu, který v současnosti představuje v mnoha programech nejčastější indikaci. Přibližně jednu dekádu se transplantace jater standardně provádí pro hilový cholangiocelulární karcinom a omezeně pro neresekovatelné jaterní metastázy kolorektálního karcinomu. Uvedené indikace těsně souvisejí s dynamikou lokální čekací listiny.
Liver transplantation has been considered the standard treatment method for patients with life-threatening liver disease for more than 40 years. In the initial period, it was mainly indicated for patients with a clearly unfavorable prognosis. Longer survival of recipients was thanks to the improvement in surgical techniques, intensive care, and immunosuppression leading to the targeting of patients with the perspective of long-term survival, i.e. shift away from oncological indications to patients with cirrhosis. The growing disparity between the need for transplantation and the number of donor organs has brought about the necessity of a stricter selection, which, in addition to purely medical considerations, also includes ethical issues of equal access to transplantation and the need to achieve the greatest possible transplant benefit for the widest possible range of recipients while utilizing limited resources. Changes in the epidemiology of liver diseases as well as advances in their treatment affected the development of indications. There has been a significant decrease in the representation of previously dominant viral hepatitis C. Worldwide, the number of patients transplanted for non-alcoholic steatohepatitis and alcoholic liver cirrhosis is increasing. Great development has been noted in the last decade in the field of liver cancer, especially for the indications of hepatocellular carcinoma, which is currently the most common indication in many programs. For about a decade, liver transplantation has been performed standardly for hilar cholangiocellular carcinoma and experimentally for unresectable liver metastases of colorectal cancer. These indications are closely related to the dynamics of the local waiting list.
- MeSH
- lidé MeSH
- nádory jater patologie terapie MeSH
- nealkoholová steatóza jater patologie terapie MeSH
- transplantace jater * MeSH
- výběr pacientů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Non-alcoholic fatty liver disease (NAFLD), encompassing fatty liver and its progression into nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), is one of the rapidly rising health concerns worldwide. SIRT6 is an essential nuclear sirtuin that regulates numerous pathological processes including insulin resistance and inflammation, and recently it has been implicated in the amelioration of NAFLD progression. SIRT6 overexpression protects from formation of fibrotic lesions. However, the underlying molecular mechanisms are not fully delineated. Moreover, new allelic variants of SIRT6 (N308K/A313S) were recently associated with the longevity in Ashkenazi Jews by improving genome maintenance and DNA repair, suppressing transposons and killing cancer cells. Whether these new SIRT6 variants play different or enhanced roles in liver diseases is currently unknown. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect liver metabolism and associated diseases. We present evidence that overexpression of centenarian-associated SIRT6 variants dramatically altered the metabolomic and secretomic profiles of unchallenged immortalized human hepatocytes (IHH). Most amino acids were increased in the SIRT6 N308K/A313S overexpressing IHH when compared to IHH transfected with the SIRT6 wild-type sequence. Several unsaturated fatty acids and glycerophospholipids were increased, and ceramide tended to be decreased upon SIRT6 N308K/A313S overexpression. Furthermore, we found that overexpression of SIRT6 N308K/A313S in a 3D hepatic spheroid model formed by the co-culture of human immortalized hepatocytes (IHH) and hepatic stellate cells (LX2) inhibited collagen deposition and fibrotic gene expression in absence of metabolic or dietary challenges. Hence, our findings suggest that novel longevity associated SIRT6 N308K/A313S variants could favor the prevention of NASH by altering hepatocyte proteome and lipidome.
- MeSH
- hepatocelulární karcinom * metabolismus patologie MeSH
- hepatocyty metabolismus patologie MeSH
- kolagen metabolismus MeSH
- lidé MeSH
- nádory jater * metabolismus patologie MeSH
- nealkoholová steatóza jater * genetika metabolismus patologie MeSH
- senioři nad 80 let MeSH
- sirtuiny * genetika metabolismus MeSH
- století lidé MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats. METHODS: SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated. RESULTS: Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group. CONCLUSIONS: Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats.
- MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- ateroskleróza * farmakoterapie MeSH
- dieta s vysokým obsahem tuků MeSH
- febuxostat farmakologie terapeutické užití MeSH
- inhibitory enzymů MeSH
- krysa rodu rattus MeSH
- kyselina močová MeSH
- lipidy MeSH
- nealkoholová steatóza jater * farmakoterapie patologie MeSH
- potkani inbrední SHR MeSH
- xanthinoxidasa MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Úvod: Nealkoholová steatóza pečene (non-alcoholic fatty liver disease – NAFLD) predstavuje narastajúci klinický problém už v detstve a v adolescencii. Súčasné poznatky o NAFLD naznačujú dôležitú úlohu genetických a environmentálnych rizikových faktorov v patogenéze tohto ochorenia. Väčšina pacientov s NAFLD je obéznych, NAFLD sa vyskytuje ale aj u neobéznych jedincov a naopak, u obéznych pacientov môže absentovať. V klinickej praxi je transabdominálna ultrasonografia najvyužívanejšia skríningová zobrazovacia metóda NAFLD. Cieľ: Cieľom práce bolo posúdenie vplyvu najrizikovejšieho faktora, ktorým je detská obezita, na vznik a rozvoj NAFLD. Materiál a metodika: V priebehu ultrasonografického vyšetrenia sme kvantitatívne hodnotili stupeň stukovatenia pečene (vyjadreného hepatorenálnym indexom) a následne aj tuhosť pečeňového tkaniva (vyjadrenú indexom pečeňovej fibrózy) celkovo u 240 probandov v rôznych skupinách podľa vekových a hmotnostných kritérií. Výsledky ultrasonografického vyšetrenia sme následne korelovali s vybranými antropometrickými a laboratórnymi parametrami. Výsledky: Zdraví donosení novorodenci s normálnou pôrodnou hmotnosťou mali signifikantne nižšie hodnoty hepatorenálneho indexu (hepato renal index – HRI) a indexu pečeňovej fibrózy (liver fibrosis index – LFI) v porovnaní so zdravou kontrolnou pediatrickou skupinou probandov vo vekovom rozmedzí od 10. do ukončeného 18. roku života s normálnou hmotnosťou (p < 0,001). V kontrolnej skupine pubertálnych a adolescentných pacientov sme nezaznamenali vplyv pohlavia na zmeny ultrasonografických hodnôt HRI (p = 0,332) a LFI (p = 0,339). Fyziologické hodnoty hepatorenálneho indexu sa bez ohľadu na pohlavie pohybovali v kontrolnej pediatrickej skupine v rozmedzí 1,02–1,23 (10. až 90. percentil), resp. 1,02–1,26 (5. až 95. percentil). V skupine obéznych pediatrických pacientov vo vekovom rozmedzí od 10. do ukončeného 18. roku života bola preukázaná štatisticky signifikantne vyššia hodnota HRI aj LFI v porovnaní s kontrolnou pediatrickou skupinou s normálnou hmotnosťou. V skupine obéznych pacientov sa so zvyšujúcou hodnotou BMI znižovala elasticita pečene (p = 0,005; rs = 0,310), avšak stupeň steatózy sa nemenil (p = 0,357). U obéznych pacientov sa elasticita pečeňového tkaniva znižovala aj s rastúcim obvodom pása (p < 0,01). Záver: Výsledky našej práce poukazujú na významnú asociáciu obezity a NAFLD v pediatrickej populácii. Ultrasonografické metódy stanovovania hepatorenálneho indexu a elasticity pečene majú uplatnenie v diagnostike skorých stupňov pečeňového poškodenia u obéznych pubertálnych a adolescentných pacientov s rizikom vzniku NAFLD. Okrem skorého záchytu týchto zmien sme schopní neinvazívne a v reálnom čase hodnotiť dynamiku ochorenia a efekt podávanej terapie, čím sa zlepšuje kontrola nad ochorením.
Rationale: Non-alcoholic fatty liver disease (NAFLD) is emerging clinical issue in childhood and adolescent age. Present knowledge of NAFLD suggests an important role of genetic and environmental risk factors in the pathogenesis of the disease. Most of the patients are obese, however, NAFLD also occurs in the non-obese group and interestingly, in obese individuals it may be absent. The transabdominal ultrasound examination is the most widely used imaging method for NAFLD screening. Aim: The aim of the study was to assess the impact of paediatric obesity as the main risk factor in NAFLD development. Materials and methods: The degree of steatosis (represented by hepatorenal index) and hepatic parenchyma stiffness (represented by fibrosis liver index) were quantitatively evaluated using ultrasound device in a total of 240 paediatric and adolescent patients divided in subgroups according to age and weight criteria. Results from ultrasound examination were subsequently correlated with anthropometric and laboratory parameters. Results: Hepatorenal index (HRI) and liver fibrosis index (LFI) in healthy term neonates with normal birth weight was significantly lower compared to the control group of healthy normal weight children aged 10–18 years (p <0.001). We did not observe an effect of gender on changes in HRI (p = 0.332) and LFI (p = 0.339) in teenage and adolescent controls. Regardless of gender, normal HRI values in paediatric heathy control group ranged from 1.02–1.23 (10th–90th percentile). The group of obese children aged 10–18 years had HRI and LFI values significantly higher in contrast with healthy normal weight controls. Obese individuals had liver stiffness proportional to BMI (p = 0.005, rs = 0.310), however, the steatosis degree remained unchanged (p = 0.357). Hepatic parenchyma stiffness also increased with waist circumference gain in corpulent patients (p <0.01). Conclusion: Results of this study point to a significant association of obesity and NAFLD in paediatric population. The assessment of HRI and liver stiffness using ultrasound methods have been employed in the diagnosis of early stages of hepatic changes in obese children and adolescent patients at risk of NAFLD development. In addition to the early detection in these changes, ultrasound determination enables non-invasive and real-time assessment of dynamics of the disease and the effect of the administered therapy, which improves control over the disease.
The search for non-invasive, fast, and low-cost diagnostic tools has gained significant traction among many researchers worldwide. Dielectric properties calculated from microwave signals offer unique insights into biological tissue. Material properties, such as relative permittivity (εr) and conductivity (σ), can vary significantly between healthy and unhealthy tissue types at a given frequency. Understanding this difference in properties is key for identifying the disease state. The frequency-dependent nature of the dielectric measurements results in large datasets, which can be postprocessed using artificial intelligence (AI) methods. In this work, the dielectric properties of liver tissues in three mouse models of liver disease are characterized using dielectric spectroscopy. The measurements are grouped into four categories based on the diets or disease state of the mice, i.e., healthy mice, mice with non-alcoholic steatohepatitis (NASH) induced by choline-deficient high-fat diet, mice with NASH induced by western diet, and mice with liver fibrosis. Multi-class classification machine learning (ML) models are then explored to differentiate the liver tissue groups based on dielectric measurements. The results show that the support vector machine (SVM) model was able to differentiate the tissue groups with an accuracy up to 90%. This technology pipeline, thus, shows great potential for developing the next generation non-invasive diagnostic tools.
- MeSH
- jaterní cirhóza MeSH
- játra patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nealkoholová steatóza jater * diagnóza patologie MeSH
- strojové učení MeSH
- umělá inteligence MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: U pacientů s nealkoholovou tukovou chorobou jater (NAFLD), jejímž typickým znakem je inzulinová rezistence (IR), bylo popsáno horší dlouhodobé přežívání a častější výskyt chronického onemocnění ledvin (CKD) než u pacientů bez NAFLD. Cílem naší studie bylo zhodnotit, zda má NAFLD a IR vliv na přežívání a renální funkci u pacientů po transplantaci jater (LT – liver transplantation). Metody: Naše prospektivní studie zahrnula 96 kandidátů LT, kteří byli sledováni po LT. Hodnotili jsme přežívání pacientů a výskyt CKD (definované jako odhadovaná glomerulární filtraci [eGFR] ≤ 1,00 ml/s/1,73 m2 nebo zjevná proteinurie) 5 let po LT a ke konci sledování. U pacientů bylo provedeno klinické, laboratorní, MR a elastografické vyšetření před LT a 1 rok po LT a biopsie jater 1 rok po LT. Výsledky: Z faktorů přítomných 1 rok po LT zvyšovaly riziko úmrtí ke konci sledování vyšší ALT (p = 0,021), ALP (p = 0,012), léčba everolimem (p = 0,025), hraničně významné byly vyšší obvod pasu (p = 0,058), AST (p = 0,059), HOMA-IR (p = 0,056) a fibróza stupně ≥ 3 v biopsii (p = 0,055). Kromě přítomnosti CKD již 1 rok po LT (p < 0,001) patřila mezi potransplantační nezávislé rizikové faktory CKD 5 let po LT přítomnost IR definované jako HOMA-IR ≥ 3 (odds ratio [OR] 4,33; 95% konfidenční interval [CI] 1,25–15,04; p = 0,021) a vyšší sérový vysokomolekulární (HMW) adiponektin (OR 1,25; 95% CI 1,03–1,50; p = 0,021). Z faktorů 1 rok po LT byly s nižšími hodnotami eGFR ke konci sledování spojeny diabetes léčený antidiabetiky (p = 0,008), vyšší sérové hladiny triglyceridů (p = 0,031), C-peptidu (p = 0,022) a leptinu (p = 0,002) a nižší celkový bilirubin (p = 0,006). U pacientů léčených everolimem jsme pozorovali trend k vyšším hodnotám eGFR (p = 0,055). Stupeň steatózy nebo přítomnost steatohepatitidy v biopsii 1 rok po LT neměly vliv na přežívání nebo renální funkce. Závěr: Přítomnost IR 1 rok po LT nezávisle zvyšovala riziko CKD 5 let po LT. Pacienti s vyšším HOMA-IR 1 rok po LT vykazovali trend k horšímu přežívání ke konci sledování.
Introduction: Insulin resistance (IR) is a hallmark of non-alcoholic fatty liver disease (NAFLD), which has been associated with worse long-term survival and more frequent occurrence of chronic kidney disease (CKD) than in patients without NAFLD. The aim of our study was to evaluate the impact of NAFLD and IR on survival and renal function in patients after liver transplantation (LT). Methods: Our prospective study included 96 LT candidates who were observed after LT. We evaluated patient survival and occurrence of CKD (defined as estimated glomerular filtration [eGFR] ≤1.00 mL/s/1.73 m2 or overt proteinuria) 5 years after LT and at the end of follow-up. Clinical, laboratory, MR and elastographic evaluation before and 1 year after LT were performed as well as liver biopsy 1 year after LT. Results: Of the factors present 1 year after LT, higher ALT (P = 0.021), ALP (P = 0.012) and everolimus treatment (P = 0.025) increased the risk of death at the end of follow-up, borderline significance was found also for higher waist circumference (P = 0.058), AST (P = 0.059), HOMA-IR (P = 0.056) and presence of fibrosis stage ≥3 in biopsy (P = 0.055). In addition to the presence of CKD 1 year after LT (P <0.001), other independent posttransplant risk factors of CKD 5 years after LT included presence of IR defined as HOMA-IR ≥3 (OR 4.33; 95% CI 1.25–15.04; P = 0.021) and higher serum high-molecular-weight (HMW) adiponectin (OR 1.25; 95% CI 1.03–1.50; P = 0.021). Of the factors present 1 year after LT, diabetes treated by antidiabetics (P = 0.008), higher serum levels od triglycerides (P = 0.031), C-peptide (P = 0.022) and leptin (P = 0.002) and lower total bilirubin (P = 0.006) were associated with lower eGFR at the end of follow-up. We observed a trend towards higher eGFR levels in patients treated with everolimus (P = 0.055). We did not observe an impact of grade of steatosis and presence of steatohepatitis on biopsy 1 year after LT on survival or renal functions. Conclusion: Presence of IR 1 year after LT independently increased the risk of CKD 5 year after LT. Patients with higher HOMA-IR 1 year after LT had a trend towards worse survival at the end of follow-up.
Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats trying to elucidate the underlying mechanisms. Animals were assigned into control rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric measures and biochemical analyses were performed to assess metabolic and liver function changes. The inflammatory and oxidative stress markers and the histopathology of rat liver tissues were also investigated. Groups with T2DM showed increased body weight, serum glucose, and insulin resistance. They exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and deterioration of liver function. Fasudil administration reduced body weight, insulin resistance, and raised liver enzymes. It improved the disturbed lipid profile and attenuated liver inflammation. Moreover, it slowed down the progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 expression. The present study demonstrated beneficial amelioration effect of fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving mitochondrial architecture, and inhibiting apoptosis.
- MeSH
- diabetes mellitus 2. typu * komplikace farmakoterapie MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- experimentální diabetes mellitus * komplikace farmakoterapie metabolismus MeSH
- inzulinová rezistence * MeSH
- játra metabolismus MeSH
- kinázy asociované s rho metabolismus MeSH
- krysa rodu rattus MeSH
- lipidy MeSH
- nealkoholová steatóza jater * farmakoterapie patologie MeSH
- tělesná hmotnost MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
