Protective effect of rimonabant, a canabinoid receptor 1 antagonist, on nonalcoholic fatty liver disease in a rat model through modulation of the hepatic expression of activin A and follistatin

2017 ◽  
Vol 95 (12) ◽  
pp. 1433-1441 ◽  
Author(s):  
Noha I. Hussien ◽  
Hanan I. El-kerdasy ◽  
Mohammad El-tantawy Ibrahim
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Activin A ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Tgf Β1

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality, and there is still no proven effective therapy. The endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. This study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced with a choline-deficient (CD) diet in rats, as well as to detect whether it can alter the hepatic expression of activin A and follistatin. Forty rats were distributed among 4 groups: the control group, the rimonabant treatment group (normal rats that received rimonabant); the CD diet group (NAFLD induced with a CD diet); and the CD diet + rimonabant group (NAFLD treated with rimonabant). It was found that the CD diet caused significant increase in liver index, serum levels of liver enzymes, malondialdehyde (MDA), TGF-β1, activin A, and CB1 expression in liver tissue, with a significant decrease in glutathione peroxidase (GSH-Px) and follistatin mRNA expression in liver tissues. The administration of rimonabant significantly improved all of the studied parameters compared with the group fed the CD diet alone. Histopathological examination supported these results. We concluded that rimonabant significantly counteracted NAFLD induced with the CD diet by decreasing oxidative stress and hepatic expression of TGF-β1, and modulating the hepatic expression of activin A and follistatin.

Non-Alcoholic Fatty Liver Disease in Overweight Children and its Relationship with Retinol Serum Levels

2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Fatty Liver Disease ◽  
Thiobarbituric Acid ◽  
Serum Levels ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.

scholarly journals Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takuya Kawamura ◽  
Hiroaki Tanaka ◽  
Ryota Tachibana ◽  
Kento Yoshikawa ◽  
Shintaro Maki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fetal Growth ◽  
Fetal Programming ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Control Group ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractWe aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.

scholarly journals High-fructose feeding does not induce steatosis or non-alcoholic fatty liver disease in pigs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nikolaj H. Schmidt ◽  
Pia Svendsen ◽  
Julián Albarrán-Juárez ◽  
Søren K. Moestrup ◽  
Jacob Fog Bentzon
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Histopathological Examination ◽  
De Novo Lipogenesis ◽  
Large Animal ◽  
Alcoholic Fatty Liver ◽  
High Fructose ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition that has been linked to high-fructose corn syrup consumption with induction of hepatic de novo lipogenesis (DNL) as the suggested central mechanism. Feeding diets very high in fructose (> 60%) rapidly induce several features of NAFLD in rodents, but similar diets have not yet been applied in larger animals, such as pigs. With the aim to develop a large animal NAFLD model, we analysed the effects of feeding a high-fructose (HF, 60% w/w) diet for four weeks to castrated male Danish Landrace-York-Duroc pigs. HF feeding upregulated expression of hepatic DNL proteins, but levels were low compared with adipose tissue. No steatosis or hepatocellular ballooning was seen on histopathological examination, and plasma levels of transaminases were similar between groups. Inflammatory infiltrates and the amount of connective tissue was slightly elevated in liver sections from fructose-fed pigs, which was corroborated by up-regulation of macrophage marker expression in liver homogenates. Supported by RNA-profiling, quantitative protein analysis, histopathological examination, and biochemistry, our data suggest that pigs, contrary to rodents and humans, are protected against fructose-induced steatosis by relying on adipose tissue rather than liver for DNL.

Relationship of serum vaspin, nafld fibrosis score to ultrasonographic detection and quantification of steatosis in nonalcoholic fatty liver disease patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Essam Mohamed Byoumy ◽  
Moataz Mohamed Sayed ◽  
Shereen Abo Baker Abd El-Rahman ◽  
Sara Abd Elkader Al-Nakib ◽  
Mohamed Magdy Salama ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Control Group ◽  
P Value ◽  
Fibrosis Score ◽  
Alcoholic Fatty Liver ◽  
Nafld Fibrosis Score ◽  
Detection And Quantification

Abstract Background Ectopic hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of non-alcoholic fatty liver disease (NAFLD). The aim of the study was to evaluate and validate the diagnostic value of serum vaspin, NAFLD Fibrosis Score and sonograghic parameters in detection and quantification of liver steatosis and determining further need for liver biopsy or other means to establish NAFLD diagnosis. Methods This study was carried out on 60 patients having bright liver in ultrasonography and 30 healthy persons as controls. The subjects were divided into the following groups; group A: 30 age and sex matched healthy volunteers (control group), group B: 20 patients with fatty liver grade I, group C: 20 patients with fatty liver grade II and group D: 20 patients with fatty liver grade III. Results serum vaspine levels and NAFLD fibrosis score, were significantly higher in patients than in controls with p-value:&lt;0.001. There was a significant positive correlation between NAFLD fibrosis score and serum vaspin and ultrasonographic findngs of NAFLD with p-value: &lt;0.001. Conclusion Vaspin seem to be the most suitable non-invasive biomarker in predicting both intrahepatic lipid contents in NAFLD group.

scholarly journals Non alcoholic fatty liver disease is a predictor of subclinical Carotid Atherosclerosis in the presence of Metabolic Syndrome

2019 ◽  
Vol 16 (1) ◽  
pp. 39-45
Author(s):  
Cemal Kemaloglu ◽  
Melek Didem Kemaloglu
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Carotid Atherosclerosis ◽  
Controlled Study ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Alcoholic Fatty Liver Disease

Objective: The aim of this study is to identify the relationship between carotid intima-media thickness (c-imt) and non-alcoholic fatty liver disease (NAFLD), and to determine whether NAFLD is an independent predictor for the progression of atherosclerosis.  Method: This is a prospective randomized controlled study. 103 NAFLD patients who have hepatosteatosis with grade II and above were enrolled in this study. Patients were divided into NAFLD with metabolic syndrome (MS) and NAFLD without MS groups and compared with 50 healthy people. Basal demographic characteristics and C-imt of all patients and control group were measured.  Results: C-imt and carotid cross sectional area rates in the NAFLD groups were significantly higher than those in the control group. The mean and max. c-imt levels were significantly higher in the NAFLD group with metabolic syndrome (p<0,001). Homeostatic Model of Assessment-Insulin Resistance (HOMA-IR) levels were increased in the group with metabolic syndrome than those in the group without metabolic syndrome, with statistical significance (p<0.001). There was no difference in c-imt levels between HOMA-IR positive and negative groups (p=0.254) in patients with NAFLD and without metabolic syndrome. There was only a mild positive corelation between c-imt levels and high sensitive C-Reactive protein (hs-CRP) levels in metabolic syndrome positive group (p=0.026 r=0.30).  Conclusion: NAFLD was a significant predictor to determine the increased risk of carotid atherosclerosis. 

scholarly journals Biochemical changes in Non-alcoholic fatty liver disease (NAFLD): A study in Nepalese Population

2017 ◽  
Vol 2 (2) ◽  
pp. 15-20
Author(s):  
Pooja Maharjan ◽  
Puspa Raj Khanal ◽  
Narayan Prasad Parajuli ◽  
Govardhan Joshi ◽  
Hridaya Parajuli ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Biochemical Parameters ◽  
Developed Countries ◽  
Western World ◽  
Control Group ◽  
P Value ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common liver problem in the western world and is a clinicopathologic entity increasingly recognized as a major health burden in developed countries. Different laboratory tests are extremely useful in achieving a better understanding of diseases, and thereby, allow making decision for better management. The examination of different biochemical parameters usually provides excellent clues to the cause of the disease. The present study was conducted with the aim to assess the biochemical markers in Non alcoholic fatty liver disease (NAFLD) patients in Nepalese population.Methods: The biochemical parameters were investigated in 75 NAFLD patients, and 70 normal participants. The diagnosis of hepatic steatosis was established by abdominal ultrasound examination. All patients diagnosed as NAFLD were investigated for biochemical parameters and see the relationship between NAFLD and control was studied.Results: The findings of all biochemical parameters were raised in NAFLD patients in comparison with non-fatty liver control group and the differences were found to be statistically (P value less than 0.005) significant.Conclusions: NAFLD is associated with changes in biochemical parameters in cases of NAFLD. Its early detection will help in modifying the disease course, delaying complications and will also play a major role in preventive cardiology.Ann. Clin. Chem. Lab. Med. 2016:2(2);15-20

scholarly journals Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals

2010 ◽  
Vol 47 (2) ◽  
pp. 165-169 ◽  
Author(s):  
Ana Lúcia Farias de Azevedo Salgado ◽  
Luciana de Carvalho ◽  
Ana Claudia Oliveira ◽  
Virgínia Nascimento dos Santos ◽  
Jose Gilberto Vieira ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Resistance Index ◽  
Control Group ◽  
Oral Glucose ◽  
Healthy Individuals ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistance Index ◽  
Alcoholic Fatty Liver Disease

CONTEXT: Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. OBJECTIVE: To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. METHODS: One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (µU/L) x fasting glucose (nmol/L)/22.5. RESULTS: NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95%), sensitivity (Se): 85%, specificity (Sp): 83%] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72%, Sp = 94%]. CONCLUSION: HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals.

scholarly journals Simple Resistance Exercise for 24 Weeks Decreases Alanine Aminotransferase Levels in Patients with Non-Alcoholic Fatty Liver Disease

2017 ◽  
Vol 01 (01) ◽  
pp. E2-E7 ◽  
Author(s):  
Atsushi Takahashi ◽  
Hiromichi Imaizumi ◽  
Manabu Hayashi ◽  
Ken Okai ◽  
Kazumichi Abe ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Resistance Exercise ◽  
Exercise Therapy ◽  
Alanine Aminotransferase ◽  
Fatty Liver Disease ◽  
Exercise Group ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Exercise therapy is effective and recommended for non-alcoholic fatty liver disease (NAFLD) based on the efficacy of hepatic fat reduction. However, the efficacies of exercise therapy are based on short-term intervention. Moreover, no reports have examined whether significant reductions in serum levels of alanine aminotransferase (ALT) are achieved with exercise therapy in patients with NAFLD. The aim of this study is to assess the effects of simple resistance exercise for 24 weeks in NAFLD. 59 patients with NAFLD were assigned to a resistance exercise group (n=28) or a control group (n=31). The resistance exercise group performed 2 exercises (push-ups and squats) 3 times a week on nonconsecutive days for a trial periods of 24 weeks. Patients in the control group proceeded with regular physical activities under a restricted diet throughout the study. The effects of exercise were compared between groups after 24 weeks.Mean ALT level, homeostasis model assessment-estimated insulin resistance index and hepatic steatosis grade were all decreased in the resistance exercise group. Changes in ALT levels correlated negatively with changes in muscle:body weight ratio in the exercise group.These data demonstrate that 24 weeks of simple resistance exercise comprising squats and push-ups represents an effective treatment for NAFLD.

HEPATIC EXPRESSION OF CYCLOOXYGENASE-2 IN NON-ALCOHOLIC FATTY LIVER DISEASE

2008 ◽  
Vol 19 ◽  
pp. S42
Author(s):  
L. Giannitrapani ◽  
S. Ingrao ◽  
M. Soresi ◽  
S. Petta ◽  
A.M. Florena ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cyclooxygenase 2 ◽  
Alcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Alcoholic Fatty Liver Disease

scholarly journals Early cardiac electrical and structural changes in patients with non-obese non-alcoholic fatty liver disease

Kardiologiia ◽  
2021 ◽  
Vol 61 (5) ◽  
pp. 51-58
Author(s):  
Ekrem Aksu ◽  
Abdullah Sokmen ◽  
Murat Ispiroglu ◽  
Kadir Gisi ◽  
Enes Celik ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Patient Group ◽  
Fatty Liver Disease ◽  
Structural Changes ◽  
Left Ventricular ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

Background    Obese non-alcoholic fatty liver disease (NAFLD) was found to increase the risk of developing atrial fibrillation (AF) regardless of the metabolic syndrome subgroups that may accompany it. In this study, the effect of NAFLD on the structural and electrical functions of the heart was investigated using tissue Doppler echocardiography (TDE) in non-obese NAFLD patients without any known risk factors for AF.Material and methods    The study included 43 female patients (31.3±3.8 years), who had stage 2–3 hepatosteatosis detected by liver ultrasonography and diagnosed as non-obese NAFLD (patient group), and 31 healthy women (control group, 32.5±3.6 years). In addition to standard echocardiographic parameters, inter- and intra-atrial electromechanical delay (EMD) were evaluated by TDE.Results    Interatrial EMD (PA lateral – PA tricuspid) and intraatrial EMD (PA septum – PA tricuspid) were significantly longer in patient group (16.1±3.4 vs. 12.5±2.3 ms, p<0.001, and 8.4±1.6 vs. 6.6±1.6 ms, p<0.001, respectively). At the subclinical level. atrial size, left ventricular diastolic function, and left ventricular wall thickness measurements were greater in the patient group.Conclusion    Inter-atrial and intra-atrial EMD were detected in young women with non-obese NAFLD. In addition, at the subclinical level, structural and functional impairment was detected However, large-volume prospective studies are required to cobfirm these findings regarding the development of AF in non-obese NAFLD patients. 

Sign in / Sign up

Export Citation Format

Share Document