scholarly journals PO-103 The mechanism of long-term regular exercise intervention on liver injury in patients with NAFLD based on miR-146a regulation of TLR4/NF-KB signaling pathway

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Qi Peng ◽  
Jiaqin Chen ◽  
Wei Chen ◽  
Chang Feng Shao ◽  
Afang Yuan

Objective To investigate the effects of long-term regular exercise on hepatic function in patients with non-alcoholic fatty liver (NAFLD) using blood biochemistry and liver fibrosis markers, and to compare the differential expression of cytokines related to TLR4/NF-KB signaling pathway. A preliminary discussion was made on its regulation mechanism. Methods Forty patients with NAFLD diagnosed in the Hunan Normal University School of Medicine, according to the degree of steatosis and exercise intervention, the patients were divided into control group (NAFLD group) 20 cases and long-term regular exercise group 20 cases, and the same time in our hospital Twenty patients with physical examination were normal controls; general data of all subjects, ALT, AST, GGT, serum type III procollagen (PCIII), hyaluronan (HA), and type IV collagen (CIV) were examined; Fluorescent quantitative PCR was used to detect the differential expression of TLR4/NF-KB signaling pathway-related cytokines and miR-146a in the blood of each group of subjects, revealing the effects and possible mechanisms of long-term regular exercise on liver fibrosis. Results Compared with the normal group, the levels of serum ALT, AST, GGT, PCIII, HA, and CIV in the non-alcoholic fatty liver patients were significantly lower in the long-term regular exercise group than in the control group; blood TLR4, NF-KB, MY-D88 Compared with the control group, the gene expression level was significantly downregulated in the long-term regular exercise group.  Conclusions Long-term regular exercise can effectively reduce nonalcoholic inflammatory liver injury and has a clear anti-fibrotic effect. Its mechanism may be related to long-term regular exercise through regulating the TLR4/NF-KB signaling pathway related factors and the regulation of molecular miR-146a, reducing inflammation and preventing the formation of fibrosis.

2017 ◽  
Vol 01 (01) ◽  
pp. E2-E7 ◽  
Author(s):  
Atsushi Takahashi ◽  
Hiromichi Imaizumi ◽  
Manabu Hayashi ◽  
Ken Okai ◽  
Kazumichi Abe ◽  
...  

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.


Imaging ◽  
2021 ◽  
Author(s):  
Natalia M. Zhelezniakova ◽  
Anastasiia O. Rozhdestvenska ◽  
Olha V. Stepanova

Abstract Background and aim Non-alcoholic fatty liver disease (NAFLD) is closely linked to hypertension (HT). An important issue remains the search for non-invasive tests to NAFLD detection in the early stages of liver fibrosis. The objective of the study was to evaluate the diagnostic and prognostic value of kallistatin in assessing the liver fibrosis progression in NAFLD and HT patients. Patients and methods One hundred fifteen patients with NAFLD with and without HT were examined, the control group consisted of 20 relatively healthy volunteers. Plasma kallistatin level measurement, ultrasound steatometry and elastography were performed in all patients. Results Kallistatin level was 65.03 ng mL−1 (95% CI 61.38; 68.68), 83.42 ng mL−1 (95% CI 81.89; 84.94) and 111.70 ng mL−1 (95% CI 106.14; 113.22) in patients with NAFLD and HT, isolated NAFLD and control group, respectively. There were significant differences in the liver parenchyma condition between groups. Kallistatin levels strongly inversely correlated with the attenuation coefficient and the mean liver stiffness in NAFLD and HT (rs = −0.70) and in the isolated NAFLD patients (rs = −0.56; rs = −0.68, respectively). Kallistatin level was 71.82 ng mL−1 (95% CI 70.16; 79.51) and 58.62 ng mL−1 (95% CI 55.81; 64.45) in patients with HT stage I and HT stage II, respectively (P < 0.001). Conclusions Concomitant HT in NAFLD patients is associated with greater severity of fatty and fibrotic liver changes. The course of NAFLD is accompanied by decrease in kallistatin level. Increased degree of liver steatosis and fibrosis, inflammation activity, increased BMI and increased stage of HT lead to inhibition of kallistatin activity. Kallistatin may be considered as a biomarker for progression assessment of NAFLD with or without HT.


2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  

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.


Choonpa Igaku ◽  
2020 ◽  
Vol 47 (6) ◽  
pp. 241-248
Author(s):  
Hirohito TAKEUCHI ◽  
Katsutoshi SUGIMOTO ◽  
Hisashi OSHIRO ◽  
Kunio IWATSUKA ◽  
Shin KONO ◽  
...  

2018 ◽  
Vol 69 (4) ◽  
pp. 961-964
Author(s):  
Andrei Vasile Olteanu ◽  
Georgiana Emmanuela Gilca Blanariu ◽  
Gheorghe Gh. Balan ◽  
Dana Elena Mitrica ◽  
Elena Gologan ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) has become of major interest worldwide, it is estimated that more than 20% of the general population suffer from liver steatosis. NAFLD is highly associated with metabolic risk factors like type 2 diabetes mellitus, obesity and dyslipidemia, the patients diagnosed with NAFLD should adopt a high fiber low calorie diet, with reduced saturated fat and carbohydrates content, leading to weight loss and improvement of metabolic profile. Our study is aiming to shape the profile of the patient interested in being informed related to food quality and chemical composition and to evaluate the aspects on the food products label which are important for the customer. Between June 2017 and December 2017, 83 patients diagnosed with NASH were included in the study, representing the study group, while 33 subjects, without metabolic syndrome or digestive diseases, selected from patient list belonging to two general practitioners, constituted the control group. Related to the interest of being informed about the chemical composition and nutritional value of the products bought, the study showed a low interest for the provided information on nutritional value. lack of confidence in the provided information and complexity of the information are understandable, the high number of subject reasoning through lack of immediate clinical benefit is surprising. Among the healthy population the willingness to pay attention to this aspect is extremely low.


2016 ◽  
Vol 3 (5) ◽  
pp. 143
Author(s):  
Fatemeh Almasi ◽  
Mozafar Khazaei ◽  
Shima Chehrei ◽  
Ali Ghanbari

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n = 6). Animals in experimental groups were received high fructose diet (70%) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1,000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey’s post-hoc multiple comparison test and P < 0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P < 0.05) and serum lipid profiles (P < 0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P < 0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.


2019 ◽  
Vol 22 (3) ◽  
pp. 194-200 ◽  
Author(s):  
Xiang Liu ◽  
Zhi-Hong Xie ◽  
Chen-Yuan Liu ◽  
Ying Zhang

Background: Chinese herbal monomer hairy Calycosin is a flavonoid extracted from Radix astragali. Aims and Scope: The aim of the research was to investigate the effect and mechanism of Hairy Calycosin on Non-Alcoholic Fatty Liver Dieases (NAFLD) in rats. Materials and Methods: 60 rats were randomly divided into 6 groups, then NAFLD rat models were prepared and treated with different doses of Hairy Calycosin (0.5, 1.0, 2.0 mg/kg) or Kathyle relatively. Results: Both 1.0 mg/kg and 2.0 mg/kg Hairy Calycosin treatment could significantly increase the serum Superoxide Dismutase (SOD) content of the model rats and reduce the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Free Fatty Acid (FFA), IL-6, tumor necrosis factor-alpha (TNF-α) and liver homogenate malondialdehyde (MDA), while 2.0 mg/kg Hairy Calycosin can down-regulate liver tissue cytochrome p450 2E1 (CYP2E1). In the electron microscope, compared with the model control group, the mitochondrial swelling in the hepatocytes of Hairy Calycosin (1.0, 2.0 mg/kg) treatment group was significantly reduced, the ridge on the inner membrane of mitochondria increased, and the lipid droplets became much smaller. Conclusion: Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, and reduce the levels of serum TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of liver tissue, and down-regulate the expression of CYP2E1, inhibit apoptosis of hepatocytes.


2020 ◽  
Vol 18 ◽  
Author(s):  
Georgios Sfikas ◽  
Michael Psallas ◽  
Charalambos Koumaras ◽  
Konstantinos Imprialos ◽  
Evangelos Perdikakis ◽  
...  

Background: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. Aim: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. Methods: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomised to 4 groups (n=151 each): dietexercise, atorvastatin, rosuvastatin or pitavastatin for 1 year (i.e. until the next routine evaluation). Results: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001); 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs 5.62, p=0.07; FIB-4 3.42 vs 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). Conclusions : Atorvastatin, rosuvastatin and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takuya Kawamura ◽  
Hiroaki Tanaka ◽  
Ryota Tachibana ◽  
Kento Yoshikawa ◽  
Shintaro Maki ◽  
...  

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.


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