scholarly journals Prevention of Non-Alcoholic Fatty Liver Disease by Fruits and Vegetables Supplementation in Mice is Associated with Their Antioxidant Property

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1523-1523
Author(s):  
Weimin Guo ◽  
Dayong Wu ◽  
Lijun Li ◽  
Edwin Ortega ◽  
Yankun Liu ◽  
...  
Keyword(s):  
Fatty Liver Disease ◽  
Fruits And Vegetables ◽  
De Novo ◽  
Liver Steatosis ◽  
Antioxidant Property ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Freeze Dried ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives Previously we showed that supplementing a high fat diet (HFD) with a freeze-dried powder of 24 commonly consumed fruits and vegetables (F&V) prevented HFD-induced non-alcoholic fatty liver disease (NAFLD). Since the experimental diets were isocaloric with major difference being in their antioxidant content, we hypothesized that the observed effects of F&V maybe due to their antioxidant property resulting in reduced formation of inflammatory cytokines and lipids such as TNF-α and sphingolipid ceramides. Both TNF-α and ceramides have been implicated as risk factors for NFALD. The objective of this study was to test the above hypothesis. Methods Six-wk-old male C57BL/6 J mice were randomized to three groups (12/group) to receive one of the following diets: low fat (LF, 10% kcal fat), high fat (HF, 45% kcal fat), and HF plus 15% freeze-dried mixture of F&V (HF + F&V). After 20 weeks, mice were euthanized, blood and liver samples were collected for analyses of cytokines, lipids, and malondialdehyde (MDA), a lipid peroxidation biomarker, and pathways involved in ceramide formation. Results Mice fed the HF diet had significantly higher liver steatosis and plasma and/or liver ceramides, TNF-α, and MDA compared to those fed the LF diet. However, F&V supplementation prevented HF diet-induced NAFLD and significantly reduced upregulated TNF-α, ceramide, and MDA levels. Because of key role of ceramides in NFALD development, we further determined the mechanism of F&V-induced decrease in ceramide formation focusing on de novo synthesis and activity of sphingomyelinase (SMase), the enzyme that hydrolyzes sphingomyelin to generate ceramide and is modulated by oxidative stress. There was no difference in de novo ceramide synthesis; however, F&V supplementation significantly prevented HF-induced higher SMase activity. Further, liver MDA levels were positively correlated with levels of ceramides, TNF-α, SMase activity, and liver steatosis area. Conclusions The results from this study suggest that prevention of NFALD by F&V might be mediated through reduction in oxidative stress, consequently suppressing production of pro-inflammatory cytokines, and inhibiting SMase activity that leads to reduction of ceramide levels. Funding Sources This study was supported by the U.S. Department of Agriculture – Agricultural Research Service (ARS), under Agreement No. 58-1950-4-003.

scholarly journals Hepatoprotective effects ofErythrina abyssinicaLam Ex Dc against Non Alcoholic Fatty Liver Disease in Sprague Dawley Rats

2019 ◽  
Author(s):  
Felix Kanyi Macharia ◽  
Peter Waweru Mwangi ◽  
Abiy Yenesew ◽  
Frederick Bukachi ◽  
Nelly Murugi Nyaga ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Bark Extract ◽  
P Value ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
High Sugar ◽  
Freeze Dried ◽  
Alcoholic Fatty Liver Disease

ABSTRACTBackgroundNon-alcoholic fatty liver disease (NFLD) is the hepatic manifestation of the metabolic syndrome recognized as the most prevalent chronic liver disease across all age groups. NFLD is strongly associated with obesity, insulin resistance, hypertension and dyslipidemia. Extensive research efforts are geared, through pharmacological approach, towards preventing or reversing this.Erythrina abyssinicaLam ex DC is an indigenous tree used widely used in traditional medicine, including for the treatment of liver related diseases, and has been shown to possess hypoglycemic, anti-oxidant, antimicrobial and anti-plasmodia effects. The present study is aimed at establishing the effects ofE. abyssinicaon the development of Non-alcoholic fatty liver disease induced by a high-fat and high-sugar diet in rats,in-vivomodel.MethodsForty rats (40) were randomly divided into five groups: positive control (pioglitazone), Negative control (high fat/high sugar diet), low test dose (200 mg/kg), high test dose (400 mg/kg) and normal group (standard chow pellets and fresh water).The inhibitory effect of the stem bark extract ofE. abyssinicaon the development of NAFLD was evaluated by chronic administration the herb extracts to rats on a high-fat/high-sugar diet. Biochemical indices of hepatic function including serum lipid profile, serum aspartate transaminase and alanine transaminase levels were then determined. Histological analysis of liver samples was carried out to quantify the degree of steato-hepatitis. Liver weights were taken and used to determine the hepatic index. The data was analyzed using one-way ANOVA, and Tukey’s post-hoc tests were done in cases of significance. Histology data was analyzed using Kruskal-Wallis and Dunn’s post-hoc test was done in cases of significance. Significance was set at p<0.05.ResultsThe freeze dried extract ofE. abyssinicahad significant effects onfasting blood glucose[5.43 ± 0.17 (HF/HSD) vs 3.8 ± 0.15 (E 400 mg/kg) vs 4.54 ± 0.09 (E 200 mg/kg) vs. 4.16 ± 0.13 (PIOG) vs. 2.91 ± 0.16 (normal control): P value < 0.0001], andinsulin sensitivity[329.4 ± 13.48 mmol/L · min (HF/HSD) vs. 189.8 ± 12.11 mmol/L · min (E 400 mg/kg) vs. 233.8 ± 6.55 mmol/L· min (E 200 mg/kg) vs. 211.1 ± 7.35 mmol/L · min (PIOG) vs. 142.9 ± 11.94 mmol/L · min: P value < 0.0001],The extract had significant effects on hepatic indices including,hepatic triglycerides(P value < 0.0001),liver weights(P value < 0.0001),liver weight-body weight ratio(P value < 0.0001),serum ALT levels(P value < 0.0001),serum AST(P value < 0.0017),serum total cholesterol(P value < 0.0001),serum triglycerides(P value < 0.0001), andserum LDL-cholesterol(P value < 0.0001). The extracts however showed no significant effects onHDL-cholesterol(P value = 0.4759).Histological analysis showed that the extract appears to possess protective effects against steatosis, inflammation and hepatic ballooning, with the high dose (400mg/kg) being more hepato-protective.ConclusionThe freeze dried stem bark extract ofErythina abyssinicapossesses significant inhibitory effects against the development of NAFLD in Sprague Dawley rats.

scholarly journals BabaoDan attenuates high-fat diet-induced non-alcoholic fatty liver disease via activation of AMPK signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dandan Sheng ◽  
Shanmin Zhao ◽  
Lu Gao ◽  
Huifei Zheng ◽  
Wenting Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Density Lipoprotein ◽  
High Fat ◽  
Adipose Tissues ◽  
Alcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

Abstract Background Babaodan (BBD), a traditional Chinese medicine, has been shown to have protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effects of BBD on obesity-induced NAFLD. Methods C57BL/6 J mice were fed with normal diet, high fat diet (HFD) or HFD + BBD for 8 weeks. Weights of all mice were recorded every 3 days. At the end of the experiments, the level of livers, kidneys and adipose tissues of each animal was weighed. Blood serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) cholesterol, low density lipoprotein cholesterol (LDL-C), glucose and leptin were detected with appropriate test kits. Haematoxylin–eosin (HE), Masson trichrome and Oil Red O staining of the liver were performed. We applied immunohistochemical analysis to investigate the expression of TNF-α, IL-6 and leptin in liver tissue. The expression of genes related lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and ß-oxidation (CPT-1 and PPARα) in liver and adipose tissues was determined by RT-PCR. The expression of AMPK and p-AMPK was determined by western blot analysis. Results We found the weight of bodies and tissues (retroperitoneal fat pads, kidneys and livers) of mice fed with HFD + BBD were significantly lower than that of HFD-fed mice. And liver injury induced by HFD was relieved in mice treated with BBD, accompanied with significant reduction were observed in serum ALT/AST activities and alleviated pathological damage. The levels of glucose, TG, TC, HDL-C and LDL-C in the liver or serum were significantly decreased on HFD + BBD group compared with HFD group. Furthermore, BBD treatment reduced the level of TNF-α and IL-6 induced by HFD. The level of leptin in the liver and serum were reduced in mice fed with HFD + BBD than that of HFD-fed mice. Several lipid synthesis genes (SREBP1-c, ACC, SCD-1, LXRα and CD36) were down-regulated and that of ß-oxidation (CPT-1 and PPARα) up-regulated in HFD + BBD group compared with HFD group. In addition, BBD increased the expression of p-AMPK compared with untreated HFD group, which suggested BBD improved the activation of AMPK pathway. Conclusion In summary, our results indicate that BBD has potential applications in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism via activation of AMPK signaling.

scholarly journals Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats

2016 ◽  
Vol 116 (2) ◽  
pp. 191-203 ◽  
Author(s):  
Prasanthi Jegatheesan ◽  
Stéphanie Beutheu ◽  
Kim Freese ◽  
Anne-Judith Waligora-Dupriet ◽  
Esther Nubret ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Western Diet ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Status ◽  
Liver Injuries ◽  
Alcoholic Fatty Liver Disease

AbstractA Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague–Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (P<0·05) and Tnfα, and of toll-like receptor 4 (Tlr4) (P<0·05). Cit also improved plasma TAG and insulin levels. In the colon, it decreased inflammation (Tnfα and Tlr4 expressions) and increased claudin-1 protein expression. This was associated with higher levels of Bacteroides/Prevotella compared with rats fed the Western diet alone. Cit improves Western diet-induced liver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level.

scholarly journals Freeze-dried Si-Ni-San powder can ameliorate high fat diet-induced non-alcoholic fatty liver disease

2019 ◽  
Vol 25 (24) ◽  
pp. 3056-3068 ◽  
Author(s):  
Feng Zhu ◽  
Yong-Min Li ◽  
Ting-Ting Feng ◽  
Yue Wu ◽  
Hai-Xia Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Freeze Dried ◽  
Alcoholic Fatty Liver Disease

scholarly journals The value of the triglyceride-glucose index in the diagnosis of insulin resistance in early forms of non-alcoholic fatty liver disease

2021 ◽  
pp. 43-48
Author(s):  
A. A. Shipovskaya ◽  
N. A. Larina ◽  
I. V. Kurbatova ◽  
O. P. Dudanova
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Cytokeratin 18 ◽  
Alcoholic Fatty Liver ◽  
Triglyceride Glucose Index ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

The goal. To determine the value of the triglyceride glucose index (TGI) for the diagnosis of insulin resistance (IR) in early forms of non-alcoholic fatty liver disease (NAFLD).Materials and methods. 99 patients with NAFLD were examined: 38 (38.4%) with liver steatosis (LS) and 61 (61.6%) with steatohepatitis (SH). TGI was determined by the formula — In [fasting TG (mg / dl) × fasting glucose (mg / dl) / 2], patients with LS and SH were divided into quartiles (Q1-Q4) by increasing TGI levels with an assessment of liver tests, insulin levels (“Insulin TEST System”, Monobind Inc., USA), HOMA-IR, fragments of cytokeratin-18 (FCK-18) ("TPS ELISA, Biotech”, Sweden) and TNF-α (“Human TNFα Platinum” ELISA, eBioscience, Austria).Results. In patients with LS with a TGI increase from Q1 to Q4, HOMA-IR increased from 1.12 ± 0.48 to 6.02 ± 3.15 (p <0.05), a direct relationship was found between these indicators — r = 0.52 (p = 0.03). TGI also correlated with waist circumference — r = 0.81 (p = 0.01), cholesterol — r = 0.51 (p = 0.002), alkaline phosphatase — r = 0.41 (p = 0.02). In patients with SH, from Q1 to Q4, HOMA-IR increased from 3.15 ± 1.8 to 6.2 ± 3.04 (p <0.05), but there was no significant correlation between HOMA-IR and TGI. The levels of FCK-18 increased from Q1 to Q4-139.82 ± 72.45 to 359.75 ± 189.03 U / L (p <0.05) and TNF-α — from 6.38 ± 1.25 pg / ml up to 7.75 ± 1.09 pg / ml (p <0.05). There was a connection between TGI and the level of a marker of hepatocyte apoptosis — FCK-18 — r = 0.43 (p = 0.004).Conclusion. In liver steatosis, TGI has demonstrated its diagnostic role as a surrogate marker of insulin resistance, correlating with HOMA-IR. In steatohepatitis, TGI reflected the degree of hepatocytic apoptosis, correlating with fragments of cytokeratin-18.

scholarly journals Effect of diosmetin on young rats with high-fat diet-induced non-alcoholic fatty liver disease

2022 ◽  
Vol 20 (2) ◽  
pp. 315-320
Author(s):  
Guoying Zhang ◽  
Yuewu Yan ◽  
Xujiao Feng
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Diet Group ◽  
Control Group ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

Purpose: To determine the effect of diosmetin on young, non-alcoholic fatty liver disease (NAFLD) rats. Methods: Five groups of SD rats were used: control group, high-fat diet group, low-dose diosmetin group, medium-dose diosmetin group, and high-dose diosmetin group, each with 10 rats. After 3 months, interleukin 6 (IL-6), IL-1β) and TNF-α) were assayed. Protein expressions of p-AMPKα, CPT-1 and PPAR-α, AMPKα, SREBP-1c and FAS were assayed. Results: In the high-fat diet group, the levels of p-AMPKα, CPT-1 and PPAR-α were lower than the corresponding control values, while p-AMPKα, CPT-1 and PPAR-α levels were dose-dependently higher in all diosmetin groups than in NAFLD group (p < 0.05). There were higher levels of SREBP-1c and FAS in the high-fat diet group than in control group, while SREBP-1c and FAS levels in all diosmetin groups were dose-dependently lower than the corresponding levels in NAFLD group. Serum IL-6, IL-1β and TNF-α levels in NAFLD group were raised, relative to control values (p < 0.05). Conclusion: Diosmetin alleviates NAFLD lesions induced by high-fat diet, slows down liver cell apoptosis, and inhibits inflammation via activation of AMPK pathway. Thus, diosmetin has potentials for use in the repair of hepatic damage induced by high-fat diet.

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 A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1822
Author(s):  
Christian von Loeffelholz ◽  
Sina M. Coldewey ◽  
Andreas L. Birkenfeld
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mammalian Cells ◽  
De Novo ◽  
Adenosine Monophosphate ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

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