scholarly journals Autoantibodies directed against apolipoprotein A-1 as a potential contributor to non-alcoholic fatty liver disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Pagano ◽  
D Alfaiate ◽  
C Juillard ◽  
M Frias ◽  
A Magenta ◽  
...  
Keyword(s):  
Liver Disease ◽  
Lipid Accumulation ◽  
Hepatic Cell ◽  
Alcoholic Fatty Liver ◽  
Hepatic Cells ◽  
Apolipoprotein A ◽  
Tnf Α ◽  
Potential Contributor ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patients. Although NAFLD pathophysiology is not fully understood alterations in fat metabolism seem to play a role. Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) are a novel cardiovascular risk factor to which have been recently attributed a metabolic role in addition to a well-established macrophage-mediated inflammatory effect and have a function as a disruptor of the cholesterol pathway. Purpose This study aims at evaluating a possible role of anti-apoA-1 IgG in NAFLD. Methods Serum from 137 NAFLD patients were tested for anti-apoA-1 IgG prevalence. In vitro, SREBP1, SREBP2 expressions were assessed in the human hepatic cell line HepaRG by western blot analysis and bodipy staining was used to evaluate the lipid droplet content. Mescoscale technology platform was used to measure TNF-α, IL-6 and IL-8 cytokines/chemokines in HepaRG supernatants. Oil Red O staining was used to detect lipid accumulation in liver sections from ApoE−/− mice. Results Elevated anti-apoA-1 IgG seropositivity was found in patients with NAFLD (46%). In vitro, anti-apoA-1 IgG and not control IgG induced lipid accumulation in hepatic cells (5.9 vs 2.5, P=0.0008) and this lipid overload was associated with a high SREBP1 but not SREBP2 expression. Furthermore, anti-apoA-1 IgG and not control antibodies caused a significant large increase of the proinflammatory cytokines IL-6 (680 vs. 163 pg/mL, P=0.03) and TNF-α (391 vs 266 pg/mL, P=0.04) as well as of the chemokine IL-8 (174.1 vs. 72.6 ng/mL, P=0.03) detected in the hepatic cell supernatants. In vivo, anti-apoA-1 IgG and not control IgG also induced higher lipid accumulation in the livers of ApoE−/− mice (1.23 vs 0.53, P=0.03). Conclusion Anti-apoA-1 IgG are frequent in NAFLD, cause a strong inflammatory response and promote lipid accumulation through SREBP1 activation in human hepatic cells. We hypothesize that anti-apoA1 IgG may be a potential contributor in the development of NAFLD. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Geneva University Hospital

scholarly journals Auranofin Attenuates Non-Alcoholic Fatty Liver Disease by Suppressing Lipid Accumulation and NLRP3 Inflammasome-Mediated Hepatic Inflammation In Vivo and In Vitro

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1040
Author(s):  
Hyun Hwangbo ◽  
Min Yeong Kim ◽  
Seon Yeong Ji ◽  
So Young Kim ◽  
Hyesook Lee ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nlrp3 Inflammasome ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Hepatic Inflammation ◽  
Alcoholic Fatty Liver ◽  
Hepatic Diseases ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) causes liver dysfunction and is associated with obesity and type 2 diabetes. Chronic inflammation is associated not only with the development of NAFLD, but also with hepatic diseases, including steatohepatitis, cirrhosis, and hepatocellular carcinoma. Auranofin is a treatment for rheumatoid arthritis and has recently been reported to have potential effects against a variety of diseases, including inflammation, cancer, and viral infection. In this study, auranofin may be considered as a new treatment for the management of metabolic syndrome, as well as in the treatment of NAFLD through immunomodulation. To determine the effect of auranofin on NAFLD, C57BL/6 mice were randomly grouped, fed a regular diet or a high fat diet (HFD), and injected with normal saline or auranofin for 8 weeks. Auranofin significantly decreased the body weight, epididymal fat weight, serum aspartate aminotransferase (AST), and glucose, as well as the serum triglyceride, cholesterol, and low-density lipoprotein cholesterol levels as compared to the HFD group. We also observed that hepatic steatosis was increased in the HFD group and was suppressed by auranofin treatment. In addition, auranofin suppressed the expressions of interleukin (IL)-1β, IL-18, caspase-1, and the NOD-like receptor family pyrin domain containing 3 (NLRP3) in the liver tissue. Furthermore, the expression of NADPH oxidase 4 and peroxisome proliferator-activated receptor γ (PPARγ), which are a major source of oxidative stress and a regulator of adipogenesis, respectively, were also decreased by auranofin. In addition, primary mouse hepatocytes were incubated with lipopolysaccharide (LPS) and palmitic acid (PA) to induce lipid accumulation and hepatic inflammation for an in vitro model. Auranofin could significantly inhibit LPS- and PA-induced inflammatory activity including nitric oxide and NLRP3 inflammasome-mediated cytokines. The results of this study demonstrate that auranofin treatment inhibits the characteristics of NAFLD through the inhibition of NLRP3 inflammasome. Therefore, auranofin may have potential as a candidate for improving NAFLD symptoms.

scholarly journals How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?

2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Lipid Uptake ◽  
Cellular Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Lipid Species ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.

scholarly journals Antioxidant and Hypolipidemic Activity of Açai Fruit Makes It a Valuable Functional Food

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
Anna Virginia Adriana Pirozzi ◽  
Paola Imbimbo ◽  
Antonella D’Agostino ◽  
Virginia Tirino ◽  
Rosario Finamore ◽  
...  
Keyword(s):  
Functional Food ◽  
Subcutaneous Fat ◽  
Cell Models ◽  
Alcoholic Fatty Liver ◽  
Hypoxic Conditions ◽  
Tnf Α ◽  
Different Types ◽  
Vitro Model ◽  
Alcoholic Fatty Liver Disease

Several plant extracts are acquiring increasing value because of their antioxidant activity and hypolipidemic properties. Among them, great interest has been recently paid to açai fruit as a functional food. The aim of this study was to test the ability of açai extract in reducing oxidative stress and modulating lipid metabolism in vitro using different cell models and different types of stress. In fact, lipid peroxidation as evaluated in a HepG2 model was reduced five-fold when using 0.25 µg/mL of extract, and it was further reduced (20-fold) with the concentration increase up to 2.5 µg/mL. With the non alcoholic fatty liver disease (NAFLD)in vitro model, all concentrations tested showed at least a two-fold reduced fat deposit. In addition, primary adipocytes challenged with TNF-α under hypoxic conditions to mimic the persistent subcutaneous fat, treated with açai extract showed an approximately 40% reduction of fat deposit. Overall, our results show that açai is able to counteract oxidative states in all the cell models analysed and to prevent the accumulation of lipid droplets. No toxic effects and high stability overtime were highlighted at the concentrations tested. Therefore, açai can be considered a suitable support in the prevention of different alterations of lipid and oxidative metabolism responsible for fat deposition and metabolic pathological conditions.

scholarly journals Simulated Gastrointestinal Digestion Influences the In Vitro Hypolipidemic Properties of Coffee Pulp, a Potential Ingredient for the Prevention of Non-Alcoholic Fatty Liver Disease

Proceedings ◽  
2020 ◽  
Vol 61 (1) ◽  
pp. 19
Author(s):  
Cheyenne Braojos ◽  
Miguel Rebollo-Hernanz ◽  
Vanesa Benitez ◽  
Silvia Cañas ◽  
Yolanda Aguilera ◽  
...  
Keyword(s):  
Biological Activity ◽  
Liver Disease ◽  
Lipase Activity ◽  
Fatty Liver Disease ◽  
Bile Salts ◽  
Residual Fraction ◽  
Alcoholic Fatty Liver ◽  
Coffee Pulp ◽  
Alcoholic Fatty Liver Disease

Approximately 90% of the coffee cherry is discarded as waste during coffee bean processing. Coffee pulp has been validated as a potential safe ingredient and is a potential source of nutrients and health-promoting compounds that could be used as nutraceuticals to manage some chronic diseases. Metabolic disorders associated with dysregulated energy and cellular processes, such as obesity and hyperlipidemia, contribute to non-alcoholic fatty liver disease (NAFLD). In this sense, the main objective of this study was to evaluate the impact of an in vitro simulated digestion on the hypolipidemic properties of coffee pulp flour and the biological activity of the digested fractions of its flour and extract in HepG2 cells. The hypolipidemic properties of coffee pulp flour were tested by measuring the capacities of the residual fraction of each digestion to bind cholesterol and bile salts and to inhibit the lipase activity after simulated gastric, intestinal, and colonic in vitro digestion. The results exhibited that coffee pulp residual fraction had up to 58% (p < 0.05) more capacity to bind cholesterol, 1.9-fold (p < 0.05) higher bile salts binding capacity, and 1.5-fold (p < 0.05) higher ability to reduce the lipase activity than control residues. Likewise, the digested fractions of coffee pulp flour and extract (50–250 µg/mL) significantly (p < 0.05) alleviated the accumulation of fat (14–35%), triglycerides (5–27%), and cholesterol (9–48%) triggered by the stimulation of HepG2 cells with palmitic acid (500 µM) to simulate NAFLD. In conclusion, simulated gastrointestinal and colonic digestion improves coffee pulp hypolipidemic properties, enhancing its biological activity in cell culture models. Therefore, this coffee by-product could be an interesting potential ingredient to be used to prevent hyperlipidemia and regulate lipid metabolism.

scholarly journals LncRNA-H19 promotes hepatic lipogenesis by directly regulating miR-130a/PPARγ axis in non-alcoholic fatty liver disease

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Jun Liu ◽  
Tao Tang ◽  
Guo-Dong Wang ◽  
Bo Liu
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Hepatic Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Oil Red O Staining ◽  
Alcoholic Fatty Liver Disease ◽  
Oil Red O ◽  
Liver Tissues

Abstract Background: As one of the most common liver disorders worldwide, non-alcoholic fatty liver disease (NAFLD) begins with the abnormal accumulation of triglyceride (TG) in the liver. Long non-coding RNA-H19 was reported to modulate hepatic metabolic homeostasis in NAFLD. However, its molecular mechanism of NAFLD was not fully clear. Methods: In vitro and in vivo models of NAFLD were established by free fatty acid (FFA) treatment of hepatocytes and high-fat feeding mice, respectively. Hematoxylin and Eosin (H&E) and Oil-Red O staining detected liver tissue morphology and lipid accumulation. Immunohistochemistry (IHC) staining examined peroxisome proliferator-activated receptor γ (PPARγ) level in liver tissues. ELISA assay assessed TG secretion. Luciferase assay and RNA pull down were used to validate regulatory mechanism among H19, miR-130a and PPARγ. The gene expression in hepatocytes and liver tissues was detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Results: H19 and PPARγ were up-regulated, while miR-130a was down-regulated in NAFLD mouse and cellular model. H&E and Oil-Red O staining indicated an increased lipid accumulation. Knockdown of H19 inhibited steatosis and TG secretion in FFA-induced hepatocytes. H19 could bind to miR-130a, and miR-130a could directly inhibit PPARγ expression. Meanwhile, miR-130a inhibited lipid accumulation by down-regulating NAFLD-related genes PPARγ, SREBP1, SCD1, ACC1 and FASN. Overexpression of miR-130a and PPARγ antagonist GW9662 inhibited lipogenesis and TG secretion, and PPARγ agonist GW1929 reversed this change induced by miR-130a up-regulation. Conclusion: Knockdown of H19 alleviated hepatic lipogenesis via directly regulating miR-130a/PPARγ axis, which is a novel mechanistic role of H19 in the regulation of NAFLD.

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