scholarly journals mTORC1-Plin3 pathway is essential to activate lipophagy and protects against hepatosteatosis

2019 ◽  
Author(s):  
Marina Garcia-Macia ◽  
Adrián Santos-Ledo ◽  
Jack Leslie ◽  
Hanna Paish ◽  
Abigail Watson ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Dietary Fatty Acids ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Selective Degradation ◽  
New Treatments ◽  
Docking Protein ◽  
Human Liver Slices ◽  
Alcoholic Fatty Liver Disease

ABSTRACTDuring postprandial state, the liver is exposed to high levels of dietary fatty acids (FAs) and carbohydrates. FAs are re-esterified into triglycerides, which can be stored in lipid droplets (LDs) in the liver. Aberrant accumulation of LDs can lead to diseases such as alcoholic liver disease and non-alcoholic fatty liver disease, the latter being the most common liver pathology in western countries. Improved understanding of LD biology has potential to unlock new treatments for these liver diseases. The Perilipin (Plin) family is the group of proteins that coat LDs, controlling their biogenesis, stabilization, and preventing their degradation. Recent studies have revealed that autophagy is involved in LD degradation and, therefore, may be crucial to avoid lipid accumulation. Here, we show that a phosphorylated form of Plin3 is required for selective degradation of LDs in fibroblasts, primary hepatocytes and human liver slices. We demonstrate that oleic acid treatment induces the recruitment of the autophagy machinery to the surface of LDs. When Plin3 is silenced, this recruitment is suppressed resulting in accumulation of lipid. Plin3 pulldowns revealed interactions with the autophagy initiator proteins Fip200 and Atg16L indicating that Plin3 may function as a docking protein involved in lipophagy activation. Of particular importance, we define Plin3 as a substrate for mTORC1-dependent phosphorylation and show that this event is decisive for lipophagy. Our study therefore reveals that Plin3, and its phosphorylation by mTORC1, is crucial for degradation of LDs by autophagy. We propose that stimulating this pathway to enhance LD autophagy in hepatocytes will help protect the liver from lipid-mediated toxicity thus offering new therapeutic opportunities in human steatotic liver diseases.

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.

Liver disease

2019 ◽  
pp. 367-384
Author(s):  
Nina Vodošek Hojs ◽  
Aftab Ala ◽  
Debasish Banerjee
Keyword(s):  
Cardiovascular Disease ◽  
Liver Disease ◽  
Hepatitis C ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Liver Dysfunction ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Cardiovascular disease in patients with liver disease, previously uncommon, is rising because of an increasing incidence of non-alcoholic fatty liver disease and better survival of patients with viral hepatitis, particularly hepatitis C. Liver dysfunction alters the pharmacokinetics and pharmacodynamics of many drugs, and hence careful use and dose adjustments are necessary. This chapter describes common cardiovascular conditions and the pharmacotherapy in patients with different liver diseases.

scholarly journals Diagnostic Accuracy of Serological Markers in Viral Hepatitis and Non Alcoholic Fatty Liver Disease. A Comparative Study in Tertiary Care Hospital of Western Nepal

1970 ◽  
Vol 1 (2) ◽  
pp. 60-63
Author(s):  
Ankush Mittal ◽  
Brijesh Sathian ◽  
Nishida Chandrasekharan ◽  
Akshay Lekhi ◽  
Shamim Mohammad Farooqui ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Serological Markers ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

Background: Liver diseases is apparently increasing and emerging as a major public health problem. Worldwide,  chronic hepatitis B has  become  the tenth leading cause of death  and  persons infected with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), are about 350 million and  125 million respectively. The aim of current retrospective comparative study was concerned primarily to evaluate the significance of non invasive serological markers for diagnosing liver diseases and their predictive implications in Pokhara valley. Materials and Methods: It was a hospital based retrospective study carried out using the data maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st June 2009 and 31st   October 2010.  The variables collected were total protein, albumin, AST, ALT, total bilirubin, direct bilirubin.  Descriptive statistics and testing of hypothesis were used for the analysis. Data was analyzed using EPI INFO and SPSS 16 software. Results: Of 515 subjects, 120 were suffering from viral hepatitis and 88 had non alcoholic fatty liver disease. In cases of viral hepatitis, mean values of AST (CI 730.65 to 902.68) and ALT (CI 648.14 to 847.59) were markedly increased as compared to controls. Mild to moderate elevations in serum levels of aspartate aminotransferase (CI 43.42 to 49.49), alanine aminotransferase (CI 43.90 to 53.92) were the most common laboratory abnormalities found in patients with nonalcoholic fatty liver disease. Conclusion: Non invasive tests have demonstrated a reasonable ability to identify significant fibrosis, cirrhosis in particular, nor is it surprising that liver disease specialists and patients favour a non invasive approach.Key words: Viral hepatitis; Nonalcoholic fatty liver disease; Nepal.DOI: http://dx.doi.org/10.3126/nje.v1i2.5137 Nepal Journal of Epidemiology 2011;1 (2):60-63

scholarly journals Helicobacter pylori infection and fatty liver

2020 ◽  
pp. 146-153
Author(s):  
A. S. Sarsenbaevа ◽  
K. A. Ufimtsev ◽  
E. V. Domracheva
Keyword(s):  
Helicobacter Pylori ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Helicobacter Pylori Infection ◽  
Alcoholic Fatty Liver ◽  
Cancer Of The Stomach ◽  
The Subject ◽  
Alcoholic Fatty Liver Disease

Helicobacter pylori infection is widespread worldwide. It plays a signifi cant role in the pathogenesis of many diseases of the gastrointestinal tract, such as peptic ulcer, atrophic gastritis, and cancer of the stomach. Recently, a large number of works have appeared that indicate the association of Helicobacter pylori infection with extragastric diseases. Liver diseases, and especially fatty liver disease, are also widespread and actively studied. The association between Helicobacter pylori infection and non-alcoholic fatty liver disease has been the subject of many studies, but there is still insufficient evidence to make it clear.

Correlation between adiponectin level and the degree of fibrosis in patients with NAFLD

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Mohammed Youssef ◽  
Manal Sabry Mohamed ◽  
Ahmed El-Metwally Ahmed ◽  
Esraa Ebrahim Abdullah
Keyword(s):  
Diabetes Mellitus ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Adiponectin Level ◽  
Chronic Liver ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic Fatty Liver Disease (NAFLD) is one of the most prevalent chronic liver diseases particularly in Egypt. It is defined as accumulation of lipids inside the hepatocytes, in absence of other etiologies of hepatic damage. It is frequently associated with obesity, diabetes mellitus and metabolic syndrome. Objective To find out the correlation between the degree of liver fibrosis in Non-alcoholic Fatty Liver Disease patients and their serum Adiponectin level as a future non-invasive method for assessment of liver fibrosis to substitute liver biopsy to avoid its hazardous complication. Also to study the correlation between diabetes mellitus as well as obesity and serum Adiponetctin level. Patients and Methods 50 patients were selected to participate in our study based on our inclusion criteria. They were recruited from the Internal Medicine department, Gastro-intestinal clinic in AlDemerdash Hospital using a convenient sampling method. Diagnoses of NAFLD (Non-alcoholic fatty liver disease) was confirmed by laboratory markers (AST, ALT, Lipid profile), ultrasound as well as fibroscan examination. Results Analyzing adiponectin levels showed that -besides its significant correlation with BMI, hypertension, diabetes mellitus and dyslipidemia- it was significantly lower in high grade fibrosis group compared to low grade fibrosis group with P-value of (0.000) and a cutoff value for stage 3/4 fibrosis of about 2.31μg/ml which marked a promising hope of adeponictin being of protective value against liver fibrosis. However, more studies performed on populations of different sizes and characteristics are recommended to allow more accurate generalization of the results and hopefully exploring a new horizon for the follow up and treatment of patients with chronic liver disease especially NAFLD. Conclusion Adiponectin is an abundant adipocyte-derived protein with well-established antiatherogenic, insulin-sensitizing and anti-inflammatory properties. The liver is a major target organ for adiponectin especially in fatty liver diseases and this adipocytokine has the ability to control many liver functions including metabolism, inflammation and fibrosis. Both serum levels and hepatic adiponectin receptor expression are decreased in NAFLD. Therefore, either adiponectin itself or adiponectin-inducing agents might be of key therapeutic interest in the near future in the treatment of NAFLD.

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