scholarly journals Sodium butyrate protects mice from the development of the early signs of non-alcoholic fatty liver disease: role of melatonin and lipid peroxidation

2016 ◽  
Vol 116 (10) ◽  
pp. 1682-1693 ◽  
Author(s):  
Cheng Jun Jin ◽  
Anna Janina Engstler ◽  
Cathrin Sellmann ◽  
Doreen Ziegenhardt ◽  
Marianne Landmann ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Glucose Metabolism ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide with universally accepted treatments still lacking. Oral supplementation of sodium butyrate (SoB) has been suggested to attenuate liver damage of various aetiologies. Our study aimed to further delineate mechanisms involved in the SoB-dependent hepatic protection using a mouse model of fructose-induced NAFLD and in in vitro models. C57BL/6J mice were either pair-fed a fructose-enriched liquid diet ±0·6 g/kg body weight per d SoB or standard chow for 6 weeks. Markers of liver damage, intestinal barrier function, glucose metabolism, toll-like receptor-4 (TLR-4) and melatonin signalling were determined in mice. Differentiated human carcinoma colon-2 (Caco-2) and J774A.1 cells were used to determine molecular mechanisms involved in the effects of SoB. Despite having no effects on markers of intestinal barrier function and glucose metabolism or body weight gain, SoB supplementation significantly attenuated fructose-induced hepatic TAG accumulation and inflammation. The protective effects of SoB were associated with significantly lower expression of markers of the TLR-4-dependent signalling cascade, concentrations of inducible nitric oxide synthase (iNOS) protein and 4-hydroxynonenal protein adducts in liver. Treatment with SoB increased melatonin levels and expression of enzymes involved in melatonin synthesis in duodenal tissue and Caco-2 cells. Moreover, treatment with melatonin significantly attenuated lipopolysaccharide-induced expression of iNOS and nitrate levels in J774A.1 cells. Taken together, our results indicated that the protective effects of SoB on the development of fructose-induced NAFLD in mice are associated with an increased duodenal melatonin synthesis and attenuation of iNOS induction in liver.

scholarly journals Endotoxins and Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Takaomi Kessoku ◽  
Takashi Kobayashi ◽  
Kento Imajo ◽  
Kosuke Tanaka ◽  
Atsushi Yamamoto ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Controlled Trial ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Leaky Gut ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10–20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.

Healthy PNPLA3 Risk Allele Carriers Present with Unexpected Body Fat Composition. A Study of One ousand Subjects

2014 ◽  
Vol 23 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Agnieszka Kempinska-Podhorodecka ◽  
Marcin Krawczyk ◽  
Marta Klak ◽  
Malgorzata Blatkiewicz ◽  
Frank Lammert ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Anthropometric Characteristics ◽  
The Common ◽  
Total Fat ◽  
Alcoholic Fatty Liver Disease

Introduction: The common PNPLA3 (adiponutrin) variant p.I148M represents a major genetic driver of progression in non-alcoholic fatty liver disease (NAFLD). NAFLD is commonly associated with traits of the metabolic syndrome, therefore it is mostly suspected in obese individuals. Here, we investigate the association between the PNPLA3 variant and anthropometric traits in a cohort of healthy individuals.Patients and methods: We recruited 1,000 (500 females; age 18 - 66 years) healthy blood donors. The PNPLA3 variant was genotyped using TaqMan assays. All individuals were phenotyped with respect to anthropometric characteristics. We also determined the percentage of total fat (F%) and active tissue (TA%) of body weight.Results: Healthy carriers of the PNPLA3 [IM] and [MM] genotypes, although not differing in height from individuals with the genotype [II], displayed significantly lower body weight and lower BMI (both P = 0.005), higher TA% (P = 0.03) but lower F% (P = 0.03) and smaller waist, chest and shin circumferences (all P < 0.05). Separate analysis for males and females demonstrated an association between the [IM] and [MM] genotypes and higher TA% but lower F% (P = 0.04) in females. In males, BMI and total weight were significantly (P = 0.04) lower among carriers of the [M] allele.Discussion: Healthy individuals carrying the prosteatotic PNPLA3 allele p.I48M may be leaner as compared to the carriers of the common allele. Hence in clinical practice they might be overlooked since they do not necessarily present with the anthropometric characteristics commonly associated with severe hepatic steatosis.Abbreviations: ATX - autotaxin; BMI - body mass index; F% - total fat of body weight in %; Fkg - total fat of body weight in kilograms; GWAS - genome-wide association study; LPA - lysophosphatidic acid; NAFLD, non-alcoholic fatty liver disease; NASH - non-alcoholic steatohepatitis; PA - phosphatidic acid; PNPLA3-patatin-like phospholipase domain containing 3 (adiponutrin); TA% - active tissue of body weight in %; TAkg - active tissue of body weight in kilograms; WHR - waist-to-hip ratio.

scholarly journals Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhangya He ◽  
Xiaomin Li ◽  
Hexiang Yang ◽  
Pei Wu ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Glucose Metabolism ◽  
Vitamin C ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Hmw Adiponectin ◽  
Liver Health ◽  
Glutamyl Transferase ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18–60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, −5.00 (−10.25, −1.75) vs. High, −2.50 (−7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, −8.00 (−18.00, −1.75) vs. High, −3.50 (−13.75, 4.25), P = 0.05; Medium vs. Low, −3.00 (−9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.

scholarly journals Non-alcoholic fatty liver disease and left ventricular diastolic dysfunction in patients with metabolic syndrome

2020 ◽  
Vol 183 (11) ◽  
pp. 25-33
Author(s):  
S. N. Jadhav ◽  
V. G. Radchenko
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Diastolic Dysfunction ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Alcoholic Fatty Liver ◽  
Ventricular Diastolic Dysfunction ◽  
Alcoholic Fatty Liver Disease

The purpose of the study was to determine the frequency and nature of manifestations of left ventricular diastolic dysfunction in patients with non-alcoholic fatty liver disease with the background of metabolic syndrome (MS).Characteristics of patients and research methods: To solve this problem, 227 patients with MS (130 men and 97 women) were examined. The study was conducted in two phases. At the first stage, all patients with MS are divided into two groups: patients with NAFLD — 205 people and 22 — without liver damage. At the next stage, a group of NAFLD patients with left ventricular DD (n=136) (66.34%) (the main group) and patients with no DD (n=69) (33.66%) (the comparison group) were identified.Results of the study: the results of diagnostics, clinical and laboratory manifestations of left ventricular diastolic dysfunction in 136 patients with NAFLD on the background of metabolic syndrome are Presented. Significant factors of development and progression of diastolic dysfunction were identified, which include increased body weight and adipose tissue, insulin resistance, dyslipidemia, hyperuricemia, activity and stage of liver damage. According to the data of structural and functional changes in the myocardium, the role of diastolic dysfunction in the development of chronic heart failure in patients with NAFLD with manifestations of metabolic syndrome has been established.Conclusion: it was Found that the development of left ventricular diastolic dysfunction in patients with NAFLD is due to the morphofunctional state of the liver.

scholarly journals Comparison of High Fructose Corn Syrup Versus Sucrose Consumption on Non-Alcoholic Fatty Liver Disease in Juvenile Iberian Pigs

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 691-691 ◽  
Author(s):  
Catherine Johnson ◽  
Brooke Harbottle ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Morgan Coffin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Liver Disease ◽  
Lean Mass ◽  
Fatty Liver Disease ◽  
High Fructose Corn Syrup ◽  
Alcoholic Fatty Liver ◽  
Corn Syrup ◽  
High Fructose ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder and the most common liver disease in pediatric populations. Epidemiological studies have observed a parallel increase in fructose consumption and incidence of NAFLD among children. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of high fructose corn syrup (66.5% fructose, 33.5% glucose) versus sucrose (50% fructose, 50% glucose) in the diet for 16 weeks on endpoints of NAFLD and insulin resistance. Methods 30-d-old Iberian pigs were housed in pairs and randomly assigned to receive solid diets (g/kg body weight × d) of 1) control (CON; n = 6): 0 g HFCS, 0 g SUC, and 174.03 kcal metabolizable energy (ME), 2) high-fructose corn syrup (HFCS; n = 8): 31.20 g high-fructose corn syrup, 0 g sucrose and 261 kcal ME, and 3) Sucrose (SUC; n = 6): 0 g high-fructose corn syrup, 24.04 g sucrose and 261 kcal ME for 16 consecutive weeks. Results Compared to CON, both HFCS and SUC diets increased body weight gain (P ≤ 0.001), relative liver weight (P ≤ 0.01) and leptin levels (P ≤ 0.01), and decreased percentage of lean mass composition in the animals (P ≤ 0.001). In addition, HFCS increased fasting insulin levels compared to CON (P ≤ 0.05), and decreased percentage lean mass compared to SUC (P ≤ 0.05). 75% of HFCS and 66.6% of SUC pigs showed histopathological lesions consistent with microvesicular steatosis with periportal or diffuse distribution. Serum markers of liver injury did not differ between diets, and none of the animals developed inflammation, hepatocellular ballooning, Mallory hyaline or necrosis in the liver. Metabolomics analysis revealed liver sorbitol and monosaccharide concentrations were higher in both the HFCS and SUC groups versus CON (P ≤ 0.05), while adenosine monophosphate (AMP) were higher and adenosine diphosphate levels lower in the HFCS and SUC in comparison to CON (P ≤ 0.05). Numerous phosphatidylcholines and sphingomyelins were differentially changed in the HFCS group versus CON (P ≤ 0.05). Conclusions Feeding diets high in either sucrose or high fructose corn syrup promoted obesity and steatosis in the animals. Further research is needed to investigate the mechanisms leading to increased insulin resistance in the HFCS group. Funding Sources ARI #58,873, AcornSeekers, STRIDE.

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