Effect of Fructose and 3,5-Diiodothyronine (3,5-T2) on Lipid Accumulation and Insulin Signalling in Non-Alcoholic Fatty Liver Disease (NAFLD)-Like Rat Primary Hepatocytes

2014 ◽  
Vol 46 (05) ◽  
pp. 333-340 ◽  
Author(s):  
D. Gnocchi ◽  
M. Massimi ◽  
A. Alisi ◽  
S. Incerpi ◽  
G. Bruscalupi
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Insulin Signalling ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Rat Primary Hepatocytes ◽  
Alcoholic Fatty Liver Disease

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.

GCSF deficiency attenuates non-alcoholic fatty liver disease through regulating GCSFR-SOCS3-JAK-STAT3 pathway and immune cells infiltration

2021 ◽  
Author(s):  
Yuwei Zhang ◽  
Xuefeng Zhou ◽  
Peihao Liu ◽  
Xueyang Chen ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Immune Cells ◽  
Fatty Liver Disease ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Stimulating Factor ◽  
Alcoholic Fatty Liver Disease

Granulocyte colony stimulating factor (GCSF) is a cytokine with immunomodulation effects. However, little is known about its role in metabolic diseases. In the current study we aimed to explore the role of GCSF in non-alcoholic fatty liver disease (NAFLD). GCSF-/- mice were used to investigate the function of GCSF in vivo after high fat diet (HFD). Primary hepatocytes were used for evaluating the function of GCSF in vitro. Liver immune cells were isolated and analyzed by flow cytometry. Our results showed that GCSF administration significantly increased serum triglyceride (TG) levels in patients. Circulating GCSF was markedly elevated in HFD-fed mice. GCSF-/- mice exhibited alleviated HFD-induced obesity, insulin resistance and hepatic steatosis. Extra administration of GCSF significantly aggravated palmitic acid (PA)-induced lipid accumulation in primary hepatocytes. Mechanically, GCSF could bind to granulocyte colony stimulating factor receptor (GCSFR) and regulate suppressors of cytokine signaling 3, Janus kinase, signal transducer and activator of transcription 3 (SOCS3-JAK-STAT3) pathway. GCSF also enhanced hepatic neutrophils and macrophages infiltration, thereby modulating NAFLD. These findings suggest that GCSF plays an important regulatory role in NAFLD and may be a potential therapeutic target for NAFLD.

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.

Biodegradable celastrol-loaded albumin nanoparticles ameliorate inflammation and lipid accumulation in diet-induced obese mice

2022 ◽  
Author(s):  
Ni Fan ◽  
Jia Zhao ◽  
Wei Zhao ◽  
Yanting Shen ◽  
Qingchun Song ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Obese Mice ◽  
Alcoholic Fatty Liver ◽  
Albumin Nanoparticles ◽  
Metabolic Dysfunctions ◽  
Alcoholic Fatty Liver Disease

Obesity is hallmarked by endoplasmic reticulum (ER) stress, chronic inflammation and metabolic dysfunctions. The control of obesity is the key to prevent the onset of non-alcoholic fatty liver disease, diabetes,...

scholarly journals A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation

Lab on a Chip ◽  
2019 ◽  
Vol 19 (18) ◽  
pp. 3022-3031 ◽  
Author(s):  
Beyza Bulutoglu ◽  
Camilo Rey-Bedón ◽  
Young Bok (Abraham) Kang ◽  
Safak Mert ◽  
Martin L. Yarmush ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Wide Spectrum ◽  
Progressive Increase ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) involves a progressive increase of lipid accumulation. We created a microfluidic progressive NAFLD platform using free fatty acid gradients to capture the wide spectrum of disease conditions in a single continuous liver tissue.

Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease

Gut ◽  
2010 ◽  
Vol 59 (2) ◽  
pp. 267-273 ◽  
Author(s):  
P Dongiovanni ◽  
L Valenti ◽  
R Rametta ◽  
A K Daly ◽  
V Nobili ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Insulin Receptor ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Insulin Signalling ◽  
Receptor Activity ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background/aimsThe aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance.Patients and methods702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients.ResultsThe ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage >1 and >2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis >1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of ∼70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD.ConclusionsThe ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD.

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