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1.
Int J Mol Sci ; 22(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199317

RESUMO

Empagliflozin, an established treatment for type 2 diabetes (T2DM), has shown beneficial effects on liver steatosis and fibrosis in animals and in humans with T2DM, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). However, little is known about the effects of empagliflozin on liver function in advanced NASH with liver fibrosis and without diabetes. This study aimed to assess the effects of empagliflozin on hepatic and metabolic outcomes in a diet-induced obese (DIO) and insulin-resistant but non-diabetic biopsy-confirmed mouse model of advanced NASH. Male C57BL/6JRj mice with a biopsy-confirmed steatosis and fibrosis on AMLN diet (high fat, fructose and cholesterol) for 36-weeks were randomized to receive for 12 weeks: (a) Empagliflozin (10 mg/kg/d p.o.), or (b) vehicle. Metabolic outcomes, liver pathology, markers of Kupffer and stellate cell activation and lipidomics were assessed at the treatment completion. Empagliflozin did not affect the body weight, body composition or insulin sensitivity (assessed by intraperitoneal insulin tolerance test), but significantly improved glucose homeostasis as assessed by oral glucose tolerance test in DIO-NASH mice. Empagliflozin improved modestly the NAFLD activity score compared with the vehicle, mainly by improving inflammation and without affecting steatosis, the fibrosis stage and markers of Kupffer and stellate cell activation. Empagliflozin reduced the hepatic concentrations of pro-inflammatory lactosylceramides and increased the concentrations of anti-inflammatory polyunsaturated triglycerides. Empagliflozin exerts beneficial metabolic and hepatic (mainly anti-inflammatory) effects in non-diabetic DIO-NASH mice and thus may be effective against NASH even in non-diabetic conditions.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Antígenos CD/metabolismo , Compostos Benzidrílicos/farmacologia , Biópsia , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Glucose/metabolismo , Glucosídeos/farmacologia , Homeostase/efeitos dos fármacos , Resistência à Insulina , Lactosilceramidas/metabolismo , Lipidômica , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/metabolismo
2.
J Agric Food Chem ; 69(28): 7884-7897, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34251802

RESUMO

This study investigated the effects of oleanolic acid (OA) on hepatic lipid metabolism and gut-liver axis homeostasis in an obesity-related non-alcoholic fatty liver disease (NAFLD) nutritional animal model and explored possible molecular mechanisms behind its effects. The results revealed that OA ameliorated the development of metabolic disorders, insulin resistance, and hepatic steatosis in obese rats. Meanwhile, OA restored high-fat-diet (HFD)-induced intestinal barrier dysfunction and endotoxin-mediated induction of toll-like-receptor-4-related pathways, subsequently inhibiting endotoxemia and systemic inflammation and balancing the homeostasis of the gut-liver axis. OA also reshaped the composition of the gut microbiota of HFD-fed rats by reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of butyrate-producing bacteria. Our results support the applicability of OA as a treatment for obesity-related NAFLD through its anti-inflammatory, antioxidant, and prebiotic integration responses mediated by the gut-liver axis.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Ácido Oleanólico , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ratos
5.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208774

RESUMO

Bile acids (BA) play a significant role in the pathophysiology of nonalcoholic steatohepatitis (NASH). The present study evaluates the modulation of bile acid metabolomics by atorvastatin, a cholesterol-lowering agent commonly used to treat cardiovascular complications accompanying NASH. NASH was induced in mice by 24 weeks of consuming a high-saturated fat, high-fructose, and high-cholesterol diet (F), with atorvastatin administered orally (20 mg/kg/day) during the last three weeks. Biochemical and histological analyses confirmed the effectiveness of the F diet in inducing NASH. Untreated NASH animals had significantly reduced biliary secretion of BA and increased fecal excretion of BA via decreased apical sodium-dependent bile salt transporter (Asbt)-mediated reabsorption. Atorvastatin decreased liver steatosis and inflammation in NASH animals consistently with a reduction in crucial lipogenic enzyme stearoyl-coenzyme A (CoA) desaturase-1 and nuclear factor kappa light chain enhancer of activated B-cell pro-inflammatory signaling, respectively. In this group, atorvastatin also uniformly enhanced plasma concentration, biliary secretion and fecal excretion of the secondary BA, deoxycholic acid (DCA). However, in the chow diet-fed animals, atorvastatin decreased plasma concentrations of BA, and reduced BA biliary secretions. These changes stemmed primarily from the increased fecal excretion of BA resulting from the reduced Asbt-mediated BA reabsorption in the ileum and suppression of synthesis in the liver. In conclusion, our results reveal that atorvastatin significantly modulates BA metabolomics by altering their intestinal processing and liver synthesis in control and NASH mice.


Assuntos
Atorvastatina/farmacologia , Ácidos e Sais Biliares/metabolismo , Homeostase , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Biomarcadores , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado/metabolismo , Camundongos , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/biossíntese
6.
J Med Food ; 24(6): 635-644, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34161164

RESUMO

Capsanthin is the main carotenoid compound in red paprika (Capsicum annuum L.). However, little is known about the beneficial effects of capsanthin in nonalcoholic fatty liver disease (NAFLD). In this study, the hepatoprotective activity of capsanthin was investigated in a mouse model of NAFLD. Apolipoprotein-E knockout mice were fed with normal diet, Western-type diet (WD, NAFLD model), WD with capsanthin (0.5 mg/kg of body weight/day, CAP), WD with capsanthin-rich extract (25 mg/kg of body weight/day; CRE), or WD with red paprika powder (25 mg/kg of body weight/day, RPP) for 12 weeks. The carotenoid content in CRE or RPP was analyzed using ultraperformance liquid chromatography. The capsanthin concentration in CRE was 2067 mg/100 g of dry weight, which was 63% of total carotenoids. The oral administration of CRE or capsanthin significantly reduced the WD-induced increase in body weight and lipid accumulation in the liver (vs. the RPP group). In addition, CRE or capsanthin significantly inhibited the WD-induced increase in cholesterol and low-density lipoprotein levels. Furthermore, CRE or capsanthin showed reduced levels of plasma alanine and aspartate aminotransferase (ALT and AST, respectively), suggesting a steatohepatitis protective effect. Capsanthin regulated mRNA levels of peroxisome proliferator-activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), acyl-CoA oxidase 1 (Acox1), and sterol regulatory element binding protein-1c (Srebp1c), which are associated with hepatic fatty acid metabolism. Overall, our results suggest that the capsanthin of red paprika plays a protective role against hepatic steatosis/steatohepatitis in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Xantofilas , Animais , Dieta Hiperlipídica , Fígado , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras
7.
J Transl Med ; 19(1): 235, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078383

RESUMO

BACKGROUND AND AIMS: The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro. METHODS: Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs. RESULTS: We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-ß, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways. CONCLUSION: Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.


Assuntos
Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Exenatida/farmacologia , Células Hep G2 , Humanos , Fígado , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , RNA Longo não Codificante/genética
8.
Nutrients ; 13(5)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065444

RESUMO

Resveratrol and its 2-methoxy derivative pterostilbene are two phenolic compounds that occur in foodstuffs and feature hepato-protective effects. This study is devoted to analysing and comparing the metabolic effects of pterostilbene and resveratrol on gut microbiota composition in rats displaying NAFLD induced by a diet rich in saturated fat and fructose. The associations among changes induced by both phenolic compounds in liver status and those induced in gut microbiota composition were also analysed. For this purpose, fifty Wistar rats were distributed in five experimental groups: a group of animals fed a standard diet (CC group) and four additional groups fed a high-fat high-fructose diet alone (HFHF group) or supplemented with 15 or 30 mg/kg bw/d of pterostilbene (PT15 and PT30 groups, respectively) or 30 mg/kg bw/d of resveratrol (RSV30 group). The dramatic changes induced by high-fat high-fructose feeding in the gut microbiota were poorly ameliorated by pterostilbene or resveratrol. These results suggest that the specific changes in microbiota composition induced by pterostilbene (increased abundances of Akkermansia and Erysipelatoclostridium, and lowered abundance of Clostridum sensu stricto 1) may not entirely explain the putative preventive effects on steatohepatitis.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Resveratrol/farmacologia , Estilbenos/farmacologia , Animais , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Frutose/administração & dosagem , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Ratos , Ratos Wistar
9.
Liver Int ; 41 Suppl 1: 112-118, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34155794

RESUMO

Non-alcoholic steatohepatitis (NASH) is a result of inflammation and hepatocyte injury in the presence of hepatic steatosis which can progress to cirrhosis. NASH is the most rapidly growing aetiology for liver failure and indication for liver transplantation in the United States. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Because of the absence of approved pharmacotherapy, weight loss and lifestyle modifications remain the safest and most effective first-line treatment. However, this may not be effective in patients with advanced fibrosis or cirrhosis and long-term adherence is difficult to achieve. Therefore, effective drugs are urgently needed for the treatment of NASH. Drug development targeting pathological pathways in NASH have exploded in the past decade, with numerous new drugs under investigation. This review summarizes the results of pivotal finalized phase 2 studies and provides an outline of key active studies with trial data of drugs under development.


Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Preparações Farmacêuticas , Humanos , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
10.
BMC Gastroenterol ; 21(1): 245, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074270

RESUMO

BACKGROUND: Several trend analyses on liver transplantation (LT) indications have been published in the U.S. and in other countries, but there are limited data on LT indication trends in Saudi Arabia (SA), especially since the availability of direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV). This study aimed to analyze trends in the frequency of LT indications among LT recipients in SA over a 19-year period and examine associations between etiologic-specific trends and clinicodemographic characteristics. METHODS: This retrospective study analyzed clinical and surgical data of adult patients (n = 1009) who underwent LT at the King Faisal Specialist Hospital & Research Center (Riyadh, SA) between 2001 and 2019. Spearman's rank correlation, Poisson regression, and Joinpoint regression analysis were employed to assess changes in LT etiologic trends. RESULTS: In the first period (2001-2010), the main LT indications were HCV (41.9%) and hepatitis B virus (HBV) (21.1%), but nonalcoholic steatohepatitis (NASH) (29.7%) surpassed HCV (23.7%) as the leading LT indication in the second period (2011-2019); and the trends were significant in correlation analyses [incidence rate ratio (IRR) = 1.09 (1.06-1.13) for NASH; IRR = 0.93 (0.91-0.95) for HCV]. In the Joinpoint regression analysis, increases in NASH from 2006 to 2012 (+ 32.1%) were statistically significant, as were the decreases in HCV from 2004 to 2007 (- 19.6%) and from 2010 to 2019 (- 12.1%). Similar patterns were observed in LT etiological comparisons before and after the availability of DAAs and within hepatocellular carcinoma stratifications. CONCLUSIONS: Trends in the epidemiology of LT indications among LT recipients in SA have changed over a 19-year period. Most notably, NASH has eclipsed HCV in the country due to the effective treatment strategies for HCV. These trends in NASH now need an aggressive public health response to minimize and avert future onset of additional clinical and economic strains on health care systems and LT centers in SA.


Assuntos
Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Adulto , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/cirurgia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Estudos Retrospectivos , Arábia Saudita/epidemiologia
11.
Medicine (Baltimore) ; 100(19): e25358, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106587

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which ranks only second to viral hepatitis and poses an increasingly serious challenge to global public health and economy. NAFLD has attracted more and more attention, but there is no drugs with exact curative effects are available. The commonly used drugs for the treatment of NAFLD in clinical practice are statins, such drugs, inevitably increase the burden on the live. Compared to statins, traditional Chinese medicines are believed to be "all natural" with fewer side effects, are associated with strong patient compliance. Accordingly, a great deal of clinical studies have shown that Xuefu Zhuyu decoction (XFZYD) can significantly improve the clinical symptoms and enhance the therapeutic effect. Meanwhile, a system review and meta-analysis are conducted by us to further clarify the effectiveness and safety of XFZYD for NAFLD. METHODS: We will apply to database mainly range from the English literature searches Cochrane Library, PubMed, excerpt medica database, and Web of Science to the Chinese literature China national knowledge infrastructure, Chinese biomedical literature database, VIP, and Wanfang database, randomized controlled trials (RCTs) are enrolled to evaluate the effectiveness and safety of XFZYD in the treatment of NAFLD, the enrollment of RCTs is from the establishment of the database to February 01, 2021. Simultaneously we will retrieval clinical registration tests and grey literatures. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is expressed in terms of relative risk, the continuous is represented by mean difference or standard mean difference, whether there is heterogeneity is the factor that determines the synthesis of data in fixed effect model or random effect model. Alanine aminotransferase (ALT) or Aspartic acid aminotransferase (AST) coupled with Glutamyltransferase (GGT) is considered as one of the main indicators of the NAFLD, while the pathology, imaging and diagnosis of metabolic syndrome are also auxiliary results. The last, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will provide evidence for treatment of NAFLD with XFZYD in terms of effectiveness and safety. CONCLUSION: This systematic review aims to confirm the efficacy and safety of XFZYD in the treatment of NAFLD. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/7CWRK.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Humanos
12.
Zhonghua Gan Zang Bing Za Zhi ; 29(5): 456-461, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34107584

RESUMO

Objective: To study the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on free fatty acid (FFA)-induced hepatocyte steatosis, and to explore its autophagic role in this process. Methods: Human hepatocytes were cultured in vitro to induce NAFLD cell model. Liraglutide (LRG) concentration gradient was added to observe the effect on cell survival rate and fatty degeneration of liver cells. The relationship between liraglutide and autophagy was investigated with chloroquine inhibition and rapamycin (RAPA) activation in hepatocyte steatosis. Experimental group: control group: a certain concentration of BSA was added to cells cultured in DMEM complete medium; FFA model group: fatty degeneration of hepatocytes was induced by 1mmol/L FFA (OA : PA=2 : 1); LRG group: FFA (1 mmol/L) and LRG (100 nmol/L) were added to the cells at the same time; autophagy inhibition group: FFA (1 mmol/L), LRG (100 nmol/L), and chloroquine (20 µmol/L) were added to the cells at the same time; autophagy activated group: FFA (1 mmol/L) and RAPA (1 µmol/L) were added to the cells at the same time. Oil red O staining and fully automated biochemistry analyzer were used to observe the intracellular lipidosis condition. Western blotting was used to detect the levels of autophagy-related proteins (Beclin1, P62, and LC3B). One-way analysis of variance was used to compare the means between multiple groups. Results: Within a certain concentration range, with the increase of LRG concentration, the hepatocytes survival rate was increased and the degree of intracellular lipidosis had continued to decrease. The best effect was achieved when LRG concentration reached 100nmol/L, and the difference was statistically significant when compared with the FFA group (P < 0.01). During the exploration of the relationship between the degree of hepatic steatosis and autophagy, LRG group intracellular triglyceride content was significantly lower than FFA group (P < 0.01), and the levels of Beclin1, LC3B-II/LC3B-I were higher than FFA group. Additionally, FFA group had reduced P62 level, and enhanced autophagy. Compared with the LRG group, autophagy inhibition group intracellular triglyceride content was increased (P < 0.01), while the levels of Beclin1, LC3B-II/LC3B-I was decreased, and P62 level was increased. Autophagy activated group RAPA had significantly reduced FFA-induced intrahepatic triglyceride deposition, and the changes in autophagy-related protein levels were consistent with the effect of LRG. Conclusion: GLP-1RAs can alleviates FFA-induced lipotoxic liver cell damage, and promote autophagy to improve fatty degeneration of hepatocytes in NAFLD.


Assuntos
Liraglutida , Hepatopatia Gordurosa não Alcoólica , Autofagia , Hepatócitos , Humanos , Liraglutida/farmacologia , Fígado , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
13.
Zhonghua Gan Zang Bing Za Zhi ; 29(5): 462-467, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34107585

RESUMO

Objective: To investigate the effect of baicalein in improving non-alcoholic fatty liver disease caused by high fat-induced oxidative damage in mice. Methods: Male C57BL/6J mice weighing 18-20 g were randomly divided into 4 groups: normal control group (C, 10% fat for energy), high-fat group (H, 60% fat for energy), high-fat + scutellaria baicalein group (H+B, baicalein: 400 mg·kg(-1)·bw(-1)), and baicalein control group (B, baicalein: 400 mg·kg(-1)·bw(-1)). After 12 weeks, mice were sacrificed, and the tissue samples were collected. Liver pathological changes were observed by hematoxylin and eosin staining. Mitochondrial morphology was examined by ultramicropathology. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and mitochondrial membrane potential (MMP) changing levels in the liver were determined by kit. Sestrin2 and protein carbonylation (PCOS) levels were detected by Western blotting. Small interfering RNA (siRNA) was used to knock-down the Sestrin2 protein expression in HepG2 cells. Intramyocellular lipid changes in HepG2 cells was detected by fluorescent dye BODIPY493/503. One way ANOVA was used LSD pairwise comparison method was used to test the statistical difference. Results: Compared with the normal control group, high-fat fed caused significant fatty degeneration, decreased GSH and SOD levels (P ​​< 0.05), increased MDA and protein carbonylation levels, and increased Sestrin2 expression (P < 0.05) in mice. Mitochondrial shape changes, swelling, lack of cristae, and MMP was down-regulated by 33.3% (t = 13.456, P ​​< 0.001). Baicalein intervention had effectively inhibited hepatic steatosis and oxidative damage caused by high-fat fed, and further up-regulated Sestrin2 expression, MMP (t = 10.104, P ​​< 0.001), and significantly alleviated liver damage in mice. Sestrin2 expression knock-down had further increased the intracellular lipid deposition and PCOs expression (P ​​< 0.05), and reduced baicalein ability to antagonize lipid deposition and antioxidant capacity in Hep2 cells. Conclusion: Baicalein alleviate non-alcoholic fatty liver by regulating Sestrin2 expression and high-fat fed-induced liver oxidative damage.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica/efeitos adversos , Flavanonas , Hepatócitos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo
14.
Wiad Lek ; 74(4): 957-760, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34156011

RESUMO

OBJECTIVE: The aim: To evaluate the efficiency of the proposed therapy, which included recommendations for nutrition, physical activity and treatment with rosuvastatin, omega-3 PUFA and ursodeoxycholic acid, on the indicators of the lipid profile in patients with NAFLD and prediabetes. PATIENTS AND METHODS: Materials and methods: 78 patients with impaired glucose tolerance were examined. According to the inclusion and exclusion criteria, 55 patients with prediabetes and concomitant NAFLD were included in the study. All patients underwent a comprehensive clinical examination, which included anthropometric data collection, objective examination, and venous blood sampling for laboratory tests. RESULTS: Results: The data obtained after 12 months of proposed treatment revealed a statistically significant improvement of indicators lipid profile in patients with prediabetes and NAFLD. Moreover, no significant difference between mean values of HDLC, LDLC, TG and atherogenic coefficient of almost healthy individuals and the corresponding indicators of treated patients detected. CONCLUSION: Conclusions: therapy which included recommendations for nutrition, physical activity and treatment with rosuvastatin, omega-3 PUFA and ursodeoxycholic acid significantly improved lipid metabolism in patients with prediabetes and NAFLD.


Assuntos
Ácidos Graxos Ômega-3 , Hepatopatia Gordurosa não Alcoólica , Estado Pré-Diabético , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Metabolismo dos Lipídeos , Lipídeos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estado Pré-Diabético/complicações , Estado Pré-Diabético/tratamento farmacológico
15.
Wiad Lek ; 74(4): 986-991, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34156017

RESUMO

OBJECTIVE: The aim: Of this research is to evaluate laboratory changes in the liver blood tests, carbohydrate and lipid metabolism in NAFLD patients with concomitant pre-diabetes, and to study the feasibility of their complex treatment with the inclusion of omega-3 polyunsaturated fatty acids and essential phospholipids. PATIENTS AND METHODS: Materials and methods: We have examined 55 patients with non-alcoholic fatty liver disease on the background of pre-diabetes aged 40 to 75 years. Modification of lifestyle was recommended to all patients as a basic treatment. In addition, the patients were prescribed essential phospholipids in 2 capsules 3 times a day and omega-3 polyunsaturated fatty acids 1000 mg per day for 28 patients (group 1) or rosuvastatin 10 mg per day for 27 persons (group 2). The effectiveness of the treatment was evaluated in 3 months, and the long-term outcomes were evaluated in 12 months. RESULTS: Results: Under the influence of the prescribed treatment, a hypolipidemic effect was observed in both groups, but a significant decline in the activity of alanine aminotransferase and aspartate aminotransferase occurred only under the influence of a combination of essential phospholipids and omega-3 polyunsaturated fatty acids. CONCLUSION: Conclusions: Thus, the described results allow to recommend this combination of medicines to patients with non-alcoholic fatty liver disease and concomitant pre-diabetes.


Assuntos
Ácidos Graxos Ômega-3 , Hepatopatia Gordurosa não Alcoólica , Estado Pré-Diabético , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estado Pré-Diabético/complicações , Estado Pré-Diabético/tratamento farmacológico
16.
J Biomed Nanotechnol ; 17(5): 942-951, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082879

RESUMO

Naringenin (NGN) can be used to inhibit the progression of nonalcoholic fatty liver disease (NAFLD) in mice, but its poor water solubility limits its applications. Nanostructured lipid carriers (NLCs) have recently attracted much attention in the field of nanodrug delivery systems because they increase the drug loading capacity and impressively enhance the solubility of indissolvable drugs. Herein, a thin-film dispersion method was used to prepare naringenin-loaded nanostructured lipid carriers (NGN-NLCs). These NGN-NLCs have a narrow size distribution of 171.9 ±2.0 nm, a high drug loading capacity of 23.7 ± 0.3%, a high encapsulation efficiency of 99.9 ± 0.0% and a drug release rate of 86.2 ± 0.4%. NGN- NLCs elevated the pharmacokinetic parameters (Cmax and AUC0→t) of NGN, accelerated NGN transepithelial transport in MDCK cells and intestinal absorption in the jejunum and ileum, and reduced hepatic lipid accumulation in an oleic acid (OA) plus lipopolysaccharide (LPS)-induced lipid deposition cell model in primary hepatocytes and in a methionine/choline deficient (MCD) diet-induced NAFLD mouse model. A detailed study of the mechanism showed that this NLC formulation elevated the drug release rate in simulated intestinal solutions in vitro, the transepithelial transport in MDCK cells, the oral absorption in mice and the ex vivo intestinal absorption of NGN. Thus, NGN-NLCs significantly enhanced the inhibitory effects of NGN on MCD diet induced mouse NAFLD.


Assuntos
Nanoestruturas , Hepatopatia Gordurosa não Alcoólica , Administração Oral , Animais , Portadores de Fármacos , Flavanonas , Lipídeos , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley
17.
FASEB J ; 35(6): e21458, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33948987

RESUMO

Porphyran and its derivatives possess a variety of biological activities, such as ameliorations of oxidative stress, inflammation, hyperlipemia, and immune deficiencies. In this study, we evaluated the potential efficacy of porphyran-derived oligosaccharides from Porphyra yezoensis (PYOs) in alleviating nonalcoholic fatty liver disease (NAFLD) and preliminarily clarified the underlying mechanism. NAFLD was induced by a high-fat diet for six months in C57BL/6J mice, followed by treatment with PYOs (100 or 300 mg/kg/d) for another six weeks. We found that PYOs reduced hepatic oxidative stress in mice with NAFLD, which plays a critical role in the occurrence and development of NAFLD. In addition, PYOs could markedly decrease lipid accumulation in liver by activating the IRS-1/AKT/GSK-3ß signaling pathway and the AMPK signaling pathway in mice with NAFLD. PYOs also apparently relieved the hepatic fibrosis induced by oxidative stress via downregulation of TGF-ß and its related proteins, so that liver injury was markedly alleviated. Furthermore, PYOs treatment relieved cecal microbiota dysbiosis (such as increasing the relative abundance of Akkermansia, while decreasing the Helicobacter abundance), which could alleviate oxidative stress, inflammation, and lipid metabolism, and protect the liver to a certain degree. In summary, PYOs treatment remarkably improved NAFLD via a specific molecular mechanism and reshaped the cecal microbiota.


Assuntos
Ceco/efeitos dos fármacos , Modelos Animais de Doenças , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Oligossacarídeos/farmacologia , Sefarose/análogos & derivados , Animais , Ceco/microbiologia , Disbiose/complicações , Disbiose/microbiologia , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Oligossacarídeos/química , Estresse Oxidativo , Sefarose/química , Transdução de Sinais
19.
Int J Biol Macromol ; 183: 1379-1392, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33992651

RESUMO

Gut microbiota and intestinal permeability have been demonstrated to be the key players in the gut-liver cross talk in nonalcoholic fatty liver disease (NAFLD). Lycium barbarum polysaccharides (LBPs), which seem to be a potential prebiotic, and aerobic exercise (AE) have shown protective effects on NAFLD. However, their combined effects on intestinal microecology remain unclear. This study evaluated the effects of LBP, AE, and its combination (LBP + AE) on gut microbiota composition, intestinal barrier, and hepatic inflammation in NAFLD. LBP + AE showed high abundance and diversity of gut microbiota, restored the gut microbiota composition, increased some Bacteroidetes, short chain fatty acids, but decreased Proteobacteria and the ratio of Firmicutes/Bacteroidetes. Simultaneously, LBP, AE, and LBP + AE could restore the colonic and ileum tight junctions by increasing the expression of zonula occludens-1 and occludin. They also downregulated gut-derived lipopolysaccharides (LPSs), hepatic LPS-binding proteins, inflammatory factors, and related indicators of the LPS/TLR4/NF-κB signaling pathway for the liver. Our results implied that LBP could be considered a prebiotic agent, and LBP + AE might be a promising treatment for NAFLD because it could maintain gut microbiota balance, thereby restoring intestinal barrier and exerting hepatic benefits.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/terapia , Condicionamento Físico Animal/métodos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Inflamação/terapia , Mucosa Intestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Prebióticos
20.
Free Radic Biol Med ; 171: 156-168, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33974978

RESUMO

BACKGROUND AND AIM: Obesity is a major risk factor for several diseases, including metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). The use of natural products, such as astaxanthin (ASX), a potent antioxidant compound produced by the freshwater green microalga Haematococcus pluvialis, has gained particular interest to reduce oxidative stress and inflammation, and to improve redox status, often associated with obesity. A systematic review and meta-analysis was performed to comprehensively examine the effects of ASX in animal models of diet induced obesity-associated diseases in order to inform the design of future human clinical studies for ASX use as supplement or nutraceutical. METHODS: Cinahl, Cochraine, MEDLINE, Scopus and Web of Science were searched for English-language manuscripts published between January 2000 and April 2020 using the following key words: astaxanthin, obesity, non-alcoholic fatty liver disease, diabetes mellitus type 2, NAFLD and metabolic. RESULTS: Seventeen eligible articles, corresponding to 21 animal studies, were included in the final quantitative analysis. ASX, at different concentrations and administered for different length of time, induced a significant reduction in adipose tissue weight (P = 0.05) and systolic blood pressure (P < 0.0001) in control animals. In animal models of T2D, ASX significantly reduced serum glucose levels (P = 0.04); whereas it improved several disease biomarkers in the blood (e.g. cholesterol, triglycerides, ALT and AST, P < 0.10), and reduced liver (P = 0.0002) and body weight (P = 0.11), in animal models of NAFLD. CONCLUSIONS: Supplementation of ASX in the diet has positive effects on symptoms associated with obesity related diseases in animals, by having lipid-lowering, hypo-insulin and hypoglycaemic capacity, protecting organs from oxidative stress and mitigating the immune system, as suggested in this review.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Modelos Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade , Xantofilas
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