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Background and Aims: Several chronic multifactorial diseases originate from energy unbalance between food intake and body energy expenditure, including non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiovascular disorders. Vascular endothelium plays a central role in body homeostasis, and NAFLD is often associated with endothelial dysfunction (ED), the first step in atherosclerosis. Both sugars and fatty acids (FAs) are fuel sources for energy production, but their excess leads to liver steatosis which may trigger ED through a network of mechanisms which need to be clarified. Here, we investigated the crosstalk pathways between in vitro cultured steatotic hepatocytes (FaO) and endothelial cells (HECV) being mediated by soluble factors.Methods and Results: We employed the conditioned medium approach to test how different extent and features of hepatic steatosis distinctively affect endothelium leading to ED. The steatogenic media collected from steatotic hepatocytes were characterized by high triglyceride content and led to lipid accumulation and fat-dependent dysfunction in HECV cells. We found a parallelism between (i) extent of hepatocyte steatosis and level of lipid accumulation in HECV cells; (ii) type of hepatocyte steatosis (with macro- or microvesicular LDs) and extent of oxidative stress, lipid peroxidation, nitric oxide release and expression of ED markers in HECV cells.Conclusions: The present findings seem to suggest that, in addition to triglycerides, other soluble mediators should be released by steatotic hepatocytes and may influence lipid accumulation and function of HECV cells. Further studies need to depict the exact profile of soluble factors involved in steatotic hepatocyte-endothelium crosstalk. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Celiac Disease (CD) is an autoimmune disease involving the small bowel, generated by the ingestion of gluten-containing foods in genetically predisposed subjects. Currently, the unique therapy for CD is the absolute adherence to gluten-free diet, but this treatment has been related to the onset of non-alcoholic fatty liver disease (NAFLD). In this systematic review, we provide an update from the most recent studies on the risk of developing NAFLD patients adhering to GFD. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed and Google Scholar from 2012 to 2021. RESULTS: In the present systematic review, eight studies investigated how GFD in CD patients may be a risk factor for the onset of NAFLD from a minimum of six months to the maximum follow-up period represented by a median of 10 years. CONCLUSIONS: Present systematic review evaluates how GFD plays a key role in NAFLD for consumption of products rich in saturated fats and carbohydrates that promotes accumulation of lipids and lead to hepatic steatosis and inflammation. [ABSTRACT FROM AUTHOR]

• Calcium signalling regulates hepatic metabolism following nutrient availability. • Altered calcium signalling induces hepatic insulin resistance and steatosis. • Calcium-targeted therapies may help to improve hepatic metabolic diseases. The flexibility between the wide array of hepatic functions relies on calcium (Ca2+) signalling. Indeed, Ca2+ is implicated in the control of many intracellular functions as well as intercellular communication. Thus, hepatocytes adapt their Ca2+ signalling depending on their nutritional and hormonal environment, leading to opposite cellular functions, such as glucose storage or synthesis. Interestingly, hepatic metabolic diseases, such as obesity, type 2 diabetes and non-alcoholic fatty liver diseases, are associated with impaired Ca2+ signalling. Here, we present the hepatocytes' toolkit for Ca2+ signalling, complete with regulation systems and signalling pathways activated by nutrients and hormones. We further discuss the current knowledge on the molecular mechanisms leading to alterations of Ca2+ signalling in hepatic metabolic diseases, and review the literature on the clinical impact of Ca2+-targeting therapeutics. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective To study the effect of trigonelline on the change of indicators of serum transaminase, lipoprotein and liver lipid of model rats with non-alcoholic fatty liver diseases and on the expression level of Bcl-2 and Bax proteins. Methods A total of 45 SD rats were randomly divided into the control group, model group and trigonelline intervention group. Rats in the control group were fed with the common diet, while rats in the model group and intervention group were fed with the high fat diet. 8 weeks later, the intervention group received the intragastric administration of trigonellin e (with the dosage of 40 mg/kg/d) for 8 weeks; while control group and model group received the intragastric administration of saline with the equal dosage. Blood was taken from the abdominal aorta of rats 8 weeks later, detecting the level of a series of indicators of ALT, AST, TG, TC, HDL-C and LDL-C in the serum. After the rats were sacrificed, detect the indicators of TG, TC, SOD and MDA in the liver tissue of rats, as well as the expression of Bcl-2 and Bax in the liver tissue. Results Results of histopathologic examination showed that the damage degree of liver for rats in the trigonelline intervention group was smaller than the one in the model group, with significantly reduced hepatic steatosis and the partially visible hepatic lobule. The levels of ALT, AST, TC and LDL-C in the serum of rats in the trigonelline group were significantly reduced, while the change in the levels of TG and HDL-C was not significantly different. The levels of TG, TC and MDA in the liver tissues were significantly decreased, while the level of SOD significantly increased; the expression of Bcl-2 protein in the liver tissues of rats in the trigonelline intervention group was significantly increased, while the expression of Bax protein significantly decreased. Conclusions The trigonelline contributes to the therapeutic effect of non-alcoholic fatty liver diseases. It can also increase the expression of Bcl-2 protein and decrease the expression of Bax protein in the liver tissues, which can protect the liver. [ABSTRACT FROM AUTHOR]

Abstract: Background and study aims: The prevalence of non-alcoholic fatty liver disease (NAFLD) appears to be increasing. The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 (PON1) activity, lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin. Patients and methods: This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex. All of them were subjected to the following investigations: abdominal ultrasonography, serum PON1 activity level, liver function tests, serum lipid profile, fasting and postprandial blood glucose and serum levels of malondialdehyde (MDA) and glutathione peroxidase (GP). NAFLD patients were further randomly classified into two groups (25 patients each), groups Ia and Ib. Only group Ia received atorvastatin 40mg tablet for 8months. Results: Obesity, dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity (i.e., there is a significant increase in lipid peroxidation rate) in group I compared with group II. After atorvastatin therapy, there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels. Conclusion: Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis (NASH). Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation, which require follow-up in patients with NAFLD. Atorvastatin may have a role in prevention of, or delay, the transformation of liver steatosis into NASH. [Copyright &y& Elsevier]

• Mitochondria are key metabolic and signalling hubs to support hepatocyte homeostasis, flexibility and survival. • Impaired mitochondrial function contributes to chronic liver diseases associated with obesity, type 2 diabetes, and NAFLD. • Therapies targeting mitochondria are effective strategies to prevent hepatic metabolic disorders. The liver is a major organ that coordinates the metabolic flexibility of the whole body, which is characterized by the ability to adapt dynamically in response to fluctuations in energy needs and supplies. In this context, hepatocyte mitochondria are key partners in fine-tuning metabolic flexibility. Here we review the metabolic and signalling pathways carried by mitochondria in the liver, the major pathways that regulate mitochondrial function and how they function in health and metabolic disorders associated to obesity, i.e. insulin resistance, non-alcoholic steatosis and steatohepatitis and hepatocellular carcinoma. Finally, strategies targeting mitochondria to counteract liver disorders are discussed. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota play important roles in insulin homeostasis and the pathogenesis of non-alcoholic fatty liver diseases (NAFLD). Yijin-Tang (YJT), a traditional Korean and Chinese medicine, is used in the treatment of gastrointestinal diseases and obesity-related disorders such as insulin resistance (IR) and NAFLD.Purpose: Our aim was to identify the microbiome-mediated effects of YJT on IR and associated NAFLD by integrating metagenomics and hepatic lipid profile.Methods: C57BL/6J mice were fed a normal chow diet (NC) or high-fat/high-cholesterol (HFHC) diet with or without YJT treatment. Hepatic lipid profiles were analyzed using liquid chromatography/mass spectrometry, and the composition of gut microbiota was investigated using 16S rRNA sequencing. Then, hepatic lipid profiles, gut microbiome, and inflammatory marker data were integrated using multivariate analysis and bioinformatics tools.Results: YJT improved NAFLD, and 39 hepatic lipid metabolites were altered by YJT in a dose-dependent manner. YJT also altered the gut microbiome composition in HFHC-fed mice. In particular, Faecalibaculum rodentium and Bacteroides acidifaciens were altered by YJT in a dose-dependent manner. Also, we found significant correlation among hepatic phosphatidylglycerol metabolites, F. rodentium, and γδ-T cells. Moreover, interleukin (IL)-17, which is secreted by the γδ-T cell when it recognizes lipid antigens, were elevated in HFHC mice and decreased by YJT treatment. In addition, YJT increased the relative abundance of B. acidifaciens in NC or HFHC-fed mice, which is a gut microbiota that mediates anti-obesity and anti-diabetic effects by modulating the gut environment. We also confirmed that YJT ameliorated the gut tight junctions and increased short chain fatty acid (SCFA) levels in the intestine, which resulted in improved IR.Conclusion: These data demonstrated that gut microbiome and hepatic lipid profiles are regulated by YJT, which improved the IR and NAFLD in mice with diet-induced obesity. [ABSTRACT FROM AUTHOR]