scholarly journals Exenatide Delays the Progression of Nonalcoholic Fatty Liver Disease in C57BL/6 Mice, Which May Involve Inhibition of the NLRP3 Inflammasome through the Mitophagy Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ning Shao ◽  
Xin-Yang Yu ◽  
Xue-Fei Ma ◽  
Wen-Jian Lin ◽  
Ming Hao ◽  
...  

Objective. This study is aimed at investigating whether exenatide (Exe) delays the progression of nonalcoholic fatty liver disease (NAFLD) in C57BL/6 mice by targeting the NLRP3 inflammasome through the autophagy/mitophagy pathway. Methods. Thirty male C57BL/6 mice were randomly divided into three groups: control group (n=10), model group (n=10), and Exe (exenatide) group (n=10). Mouse models of NAFLD and diabetes were established using a high-fat diet and streptozocin. Results. The levels of fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) in the serum were significantly reduced after Exe treatment. The body weight, liver weight/body weight, and number of lipid droplets in the liver significantly decreased in Exe-treated mice. Treatment with Exe markedly reduced the levels of liver lipids, malondialdehyde (MDA), and alanine aminotransferase (ALT) in serum and livers. The number of autophagosomes increased significantly in the Exe group. The expression of LC3A/B-II/I, Beclin-1, Parkin, and BNIP3L increased significantly, whereas NLRP3 and IL-1β proteins were suppressed after Exe treatment. Conclusion. We successfully established a mouse model of NAFLD and diabetes. Exe may reduce oxidative stress injury and inhibit the NLRP3 inflammasome by enhancing the autophagy/mitophagy pathway in liver, which has a protective effect on the liver in NAFLD and diabetes in C57BL/6 mice.

2021 ◽  
Vol 10 (15) ◽  
pp. 3380
Author(s):  
Chi-Ren Huang ◽  
Hung-Yi Chuang ◽  
Nai-Ching Chen ◽  
Shu-Fang Chen ◽  
Chung-Yao Hsu ◽  
...  

Antiepileptic drugs that can reduce aberrant metabolism are beneficial for patients. Zonisamide (ZNS) is a chemical with antiepileptic and antioxidant activities. Here, we evaluate the efficacy of ZNS therapy on reducing obesity and decreasing risks of vascular diseases and hepatic steatosis. Clinical and metabolic indicators including body weight, body mass index (BMI), serum lipid profiles, glycated hemoglobin (HbA1c), homocysteine, and an inflammatory marker, high-sensitivity C-reactive protein (hs-CRP), were assessed at baseline and at the end of 12 and 24 weeks of treatment. Nonalcoholic fatty liver disease was evaluated using the hepatic steatosis index (HSI). A body weight reduction of ≥5% was observed in 24.6% and 32.8% of patients after 12 and 24 weeks of ZNS treatment, respectively. After adjusting for age, sex, time, and the corresponding dependent variable at baseline, the generalized estimating equation analysis revealed that the body weight, BMI, serum levels of HbA1c, triglycerides, hs-CRP, and the index for HSI were significantly declined. These results suggest that ZNS provides benefits in patients with obesity and metabolic syndrome at high vascular risk.


Author(s):  
U. O. Mudra

Background. Gout is still one of the major health problems despite significant advances in treatment in recent years. It has been proved that pathogenetic mechanisms of development and progression of gout are associated with nonalcoholic fatty liver disease. Complex pathogenic treatment of patients aimed at different parts of the pathological process has recently been supplemented with the enterosorbents. Objective. The aim of the research is to study the clinical features of gout with concomitant nonalcoholic fatty liver disease (NAFLD) and to evaluate the effect of carbon enterosorbent on its course. Methods. 123 patients were involved in the study. They were divided into 2 groups: group 1 included patients with gout without liver damage, and group 2 included patients with concomitant NAFLD. Each of these groups was divided into subgroups, in which the patients received carbon enterosorbent carboline plus basic treatment. The control group consisted of 30 healthy persons. Anamnesis, physical examination, uric acid (UA), C-reactive protein (CRP) content, erythrocyte sedimentation rate (ESR) in serum were determined. Gout activity was evaluated using the Gout Activity Score (GAS). Results. Basic treatment in combination with carbon enterosorbent contributed to faster cure of intoxication, pain and joint syndromes, as well as decrease of the inflammatory process activity. Conclusions. The course of gout in the patients with concomitant NAFLD is more severe. Adding of carbon granular enterosorbent carboline in the complex treatment of patients with gout with or without concomitant NAFLD in the exacerbation phase contributes to a faster cureing dynamics of clinical and laboratory manifestations of the disease.


2019 ◽  
Vol 25 (11) ◽  
pp. e146-e147 ◽  
Author(s):  
Mitsuro Chiba ◽  
Kunio Nakane ◽  
Hitoshi Abe ◽  
Masafumi Komatsu ◽  
Haruhiko Tozawa

Abstract Nonalcoholic fatty liver disease (NAFLD) develops in ulcerative colitis (UC) and Crohn’s disease. However, there is scarce reporting on the onset of UC in patients with NAFLD. A 44-year-old man was diagnosed with UC and referred to us in 2019. His height was 166.0 cm, and body weight was 86.3 kg. The waist circumference was 93.7 cm (normal range <85) and triglyceride was 751 mg/dL. These findings, in addition to hypertension, resulted in a diagnosis of metabolic syndrome. HbA1c was normal. Ultrasonography disclosed severe fatty liver. Nonalcoholic fatty liver disease was diagnosed. He underwent 12 days of educational hospitalization for UC. A lacto-ovo-semi-vegetarian diet (1400 kcal/day), a kind of plant-based diet (PBD), was provided. He lost 4 kg, which was 4.6% of his base body weight. Triglyceride and total cholesterol decreased to the normal ranges. Transaminases and γ-glutamyl transpeptidase also decreased. His body weight decreased further after discharge. Follow-up ultrasonography indicated an improvement in hepatic enlargement. The shear wave velocity decreased from 1.11 to 0.88 m/s. His soft stool became normal stool by 2 months after discharge. Records of his health checkups revealed the presence of metabolic syndrome and abnormal liver function tests already in 2015. Thus, it was concluded that UC developed in a patient with NAFLD in this case. Plant-based diet has already been shown to be effective in inflammatory bowel disease (IBD). In the present case, NAFLD parameters were dramatically improved by PBD. Whether the improvement was due to weight loss per se or due to weight loss with PBD is to be clarified.


2020 ◽  
Vol 106 (1) ◽  
pp. e34-e44
Author(s):  
Aya Bardugo ◽  
Cole D Bendor ◽  
Inbar Zucker ◽  
Miri Lutski ◽  
Tali Cukierman-Yaffe ◽  
...  

Abstract Context The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. Objective To assess type 2 diabetes risk among adolescents with NAFLD. Design and Setting A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997–2011 and were followed until December 31, 2016. Participants A total of 1 025 796 normoglycemic adolescents were included. Interventions Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. Main Outcome Measures Type 2 diabetes incidence. Results During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47–4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). Conclusions Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.


2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Mengting Zhou ◽  
Naihua Hu ◽  
Meichen Liu ◽  
Ying Deng ◽  
Linfeng He ◽  
...  

Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients’ compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR.


Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 600 ◽  
Author(s):  
Oral ◽  
Sahin ◽  
Turker ◽  
Kocak

Background and objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as hypertension, diabetes, dyslipidemia, obesity, and hyperuricemia. We aim to investigate the relationship between uric acid and NAFLD in a non-obese and young population. Materials and Methods: This study was performed in January 2010–2019 with a group of 367 (225 patients in the NAFLD group and 142 in the control group) patients with liver biopsy-proven NAFLD or no NAFLD. Patients with NAFLD were classified according to the percentage of steatosis as follows, group I had 1–20% and group II >20%. Demographic, clinical, and laboratory (biochemical parameters) features were collected retrospectively. Results: The mean body mass index (BMI) and age of the patients were 26.41 ± 3.42 and 32.27 ± 8.85, respectively. The BMI, homeostatic model of assessment (HOMA-IR), and uric acid (UA) values of the NAFLD group were found to be significantly higher than those of the controls. A positive correlation was found between the NAFLD stage and UA. The following factors were independently associated with NAFLD: BMI, HOMA-IR, and UA. In addition, the cut-off value of UA was 4.75 mg/dl with a sensitivity of 45.8% and a specificity of 80.3%. Conclusions: UA is a simple, non-invasive, cheap, and useful marker that may be used to predict steatosis in patients with NAFLD.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Suja Rani Sasidharan ◽  
Joshua Allan Joseph ◽  
Senthilkumar Anandakumar ◽  
Vijayabalaji Venkatesan ◽  
Chandrasekharan Nair Ariyattu Madhavan ◽  
...  

Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract ofTamarindus indicaseed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLDviz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms.


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