scholarly journals Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3225
Author(s):  
Sanna Lensu ◽  
Raghunath Pariyani ◽  
Elina Mäkinen ◽  
Baoru Yang ◽  
Wisam Saleem ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Alcoholic Fatty Liver ◽  
Branched Chain Fatty Acids ◽  
Hepatic Fat ◽  
Branched Chain ◽  
Underlying Mechanisms ◽  
A Minor ◽  
Alcoholic Fatty Liver Disease

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.

scholarly journals Prebiotic Xylo-oligosaccharides Targeting Faecalibacterium prausnitzii Prevent High Fat Diet-induced Hepatic Steatosis in Rats

2020 ◽  
Author(s):  
Sanna Lensu ◽  
Raghunath Pariyani ◽  
Elina Mäkinen ◽  
Baoru Yang ◽  
Wisam Saleem ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Beta Oxidation ◽  
Alcoholic Fatty Liver ◽  
Faecalibacterium Prausnitzii ◽  
Branched Chain Fatty Acids ◽  
Hepatic Fat ◽  
Branched Chain ◽  
Underlying Mechanisms ◽  
Alcoholic Fatty Liver Disease

Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.

scholarly journals E3 ubiquitin ligase Grail promotes hepatic steatosis through Sirt1 inhibition

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Pei-Yao Liu ◽  
Cheng-Cheung Chen ◽  
Chia-Ying Chin ◽  
Te-Jung Liu ◽  
Wen-Chiuan Tsai ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Acid Synthesis ◽  
Sirtuin 1 ◽  
Nonalcoholic Fatty Liver ◽  
Expression Of Genes ◽  
Hepatic Fat ◽  
Underlying Mechanisms

AbstractIn obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.

scholarly journals Effects of a Low Dose of Caffeine Alone or as Part of a Green Coffee Extract, in a Rat Dietary Model of Lean Non-Alcoholic Fatty Liver Disease without Inflammation

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3240
Author(s):  
Ana Magdalena Velázquez ◽  
Núria Roglans ◽  
Roger Bentanachs ◽  
Maria Gené ◽  
Aleix Sala-Vila ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Low Dose ◽  
Female Rats ◽  
Green Coffee ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease is a highly prevalent condition without specific pharmacological treatment, characterized in the initial stages by hepatic steatosis. It was suggested that lipid infiltration in the liver might be reduced by caffeine through anti-inflammatory, antioxidative, and fatty acid metabolism-related mechanisms. We investigated the effects of caffeine (CAF) and green coffee extract (GCE) on hepatic lipids in lean female rats with steatosis. For three months, female Sprague-Dawley rats were fed a standard diet or a cocoa butter-based high-fat diet plus 10% liquid fructose. In the last month, the high-fat diet was supplemented or not with CAF or a GCE, providing 5 mg/kg of CAF. Plasma lipid levels and the hepatic expression of molecules involved in lipid metabolism were determined. Lipidomic analysis was performed in liver samples. The diet caused hepatic steatosis without obesity, inflammation, endoplasmic reticulum stress, or hepatic insulin resistance. Neither CAF nor GCE alleviated hepatic steatosis, but GCE-treated rats showed lower hepatic triglyceride levels compared to the CAF group. The GCE effects could be related to reductions of hepatic (i) mTOR phosphorylation, leading to higher nuclear lipin-1 levels and limiting lipogenic gene expression; (ii) diacylglycerol levels; (iii) hexosylceramide/ceramide ratios; and (iv) very-low-density lipoprotein receptor expression. In conclusion, a low dose of CAF did not reduce hepatic steatosis in lean female rats, but the same dose provided as a green coffee extract led to lower liver triglyceride levels.

scholarly journals Naringin protects against non-alcoholic fatty liver disease by promoting autophagic flux and lipophagy

2021 ◽  
Author(s):  
Lingling Guan ◽  
Lan Guo ◽  
Heng Zhang ◽  
Hao Liu ◽  
Yuan Qiao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Autophagic Flux ◽  
Mechanism Study ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background and Purpose: The autophagic degradation of lipid droplets (LDs), termed lipophagy, is the main mechanism contributing to lipid consumption in hepatocytes. The identification of effective and safe natural compounds that target lipophagy to eliminate excess lipids may be a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effects of naringin on NAFLD and the underlying mechanism. Experimental Approach: The role of naringin was investigated in mice fed a high-fat diet (HFD) to induce NAFLD, as well as in AML12 cells and primary hepatocytes stimulated by palmitate (PA). Transcription factor EB (TFEB)-knockdown AML12 cells and hepatocyte-specific TFEB-knockout mice were also used for the mechanism study. In vivo and in vitro studies were conducted using transmission electron microscopy, immunofluorescence techniques and western blot analysis. Key Results: We found that naringin treatment effectively relieved HFD-induced hepatic steatosis in mice and inhibited palmitate (PA)-induced lipid accumulation in hepatocytes. The increased p62 and LC3-II levels observed with excess lipid-support autophagosome accumulation and impaired autophagic flux. Treatment with naringin restored TFEB-mediated lysosomal biogenesis, thereby promoting the fusion of autophagosomes and lysosomes, restoring impaired autophagic flux and further inducing lipophagy. However, the knockdown of TFEB in hepatocytes or the hepatocyte-specific knockout of TFEB in mice abrogated naringin-induced lipophagy, which eliminated the therapeutic effect of naringin on hepatic steatosis. Conclusion and Implications: These results demonstrate that TFEB-mediated lysosomal biogenesis and subsequent lipophagy play essential roles in the ability of naringin to mitigate hepatic steatosis and suggest that naringin is a promising drug for treating or relieving NAFLD.

scholarly journals O-1602 Promotes Hepatic Steatosis through GPR55 and PI3 Kinase/Akt/SREBP-1c Signaling in Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 3091
Author(s):  
Saeromi Kang ◽  
Ae-Yeon Lee ◽  
So-Young Park ◽  
Kwang-Hyeon Liu ◽  
Dong-Soon Im
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Pi3 Kinase ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease is recognized as the leading cause of chronic liver disease. Overnutrition and obesity are associated with hepatic steatosis. G protein-coupled receptor 55 (GPR55) has not been extensively studied in hepatic steatosis, although its endogenous ligands have been implicated in liver disease progression. Therefore, the functions of GPR55 were investigated in Hep3B human hepatoma cells and mice fed high-fat diets. O-1602, the most potent agonist of GPR55, induced lipid accumulation in hepatocytes, which was reversed by treatment with CID16020046, an antagonist of GPR55. O-1602 also induced intracellular calcium rise in Hep3B cells in a GPR55-independent manner. O-1602-induced lipid accumulation was dependent on the PI3 kinase/Akt/SREBP-1c signaling cascade. Furthermore, we found increased levels of lysophosphatidylinositol species of 16:0, 18:0, 18:1, 18:2, 20:1, and 20:2 in the livers of mice fed a high-fat diet for 4 weeks. One-week treatment with CID16020046 suppressed high-fat diet-induced lipid accumulation and O-1602-induced increase of serum triglyceride levels in vivo. Therefore, the present data suggest the pro-steatotic function of GPR55 signaling in hepatocytes and provide a potential therapeutic target for non-alcoholic fatty liver disease.

scholarly journals Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease

2020 ◽  
Author(s):  
Mi Tian ◽  
Xinyun Li ◽  
Jingyuan Li ◽  
Jianmin Yang ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Chow Diet ◽  
Alcoholic Fatty Liver ◽  
Over Expression ◽  
Regulator Protein ◽  
Normal Chow ◽  
Alcoholic Fatty Liver Disease

Abstract Background: Liver plays an important role in lipid and glucose metabolism. Human antigen R (HuR) as an RNA regulator protein participates in many disease processes. Here, we investigated the specific role of HuR in hepatic steatosis and glucose metabolism.Methods: We investigated the level of HuR in liver from mice fed a normal chow diet (NCD) and high fat diet (HFD). Liver specific HuR knockout (HuRLKO) mice were generated and challenged with an HFD. Lipid levels and glucose metabolism index were examined. Results: HuR was downregulated in livers of HFD-fed mice. HuRLKO mice showed exacerbated HFD-induced hepatic steatosis but improved glucose tolerance as compared with controls. Consistently, HuR inhibited lipid accumulation in hepatocytes. Mechanically, HuR could bind to the mRNA of phosphatase and tensin homology deleted on chromosome 10 (PTEN), thus increasing their stability and translation. Finally, PTEN over-expression alleviated HFD-induced hepatic steatosis in HuRLKO mice.Conclusion: HuR modulates lipid and glucose metabolism through regulating PTEN expression.

scholarly journals Advances in Unhealthy Nutrition and Circadian Dysregulation in Pathophysiology of NAFLD

2021 ◽  
Vol 2 ◽  
Author(s):  
Xin Guo ◽  
Juan Zheng ◽  
Shixiu Zhang ◽  
Xiaofan Jiang ◽  
Ting Chen ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Hepatic Steatosis ◽  
Nutrient Intake ◽  
Critical Factor ◽  
Therapeutic Strategies ◽  
Alcoholic Fatty Liver ◽  
Hepatic Glucose ◽  
Metabolic Conditions ◽  
Hepatic Fat ◽  
Alcoholic Fatty Liver Disease

Unhealthy diets and lifestyle result in various metabolic conditions including metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Much evidence indicates that disruption of circadian rhythms contributes to the development and progression of excessive hepatic fat deposition and inflammation, as well as liver fibrosis, a key characteristic of non-steatohepatitis (NASH) or the advanced form of NAFLD. In this review, we emphasize the importance of nutrition as a critical factor in the regulation of circadian clock in the liver. We also focus on the roles of the rhythms of nutrient intake and the composition of diets in the regulation of circadian clocks in the context of controlling hepatic glucose and fat metabolism. We then summarize the effects of unhealthy nutrition and circadian dysregulation on the development of hepatic steatosis and inflammation. A better understanding of how the interplay among nutrition, circadian rhythms, and dysregulated metabolism result in hepatic steatosis and inflammation can help develop improved preventive and/or therapeutic strategies for managing NAFLD.

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