scholarly journals Heat Shock Protein 60 Restricts Release of Mitochondrial dsRNA to Suppress Hepatic Inflammation and Ameliorate Non-Alcoholic Fatty Liver Disease in Mice

2022 ◽  
Vol 23 (1) ◽  
pp. 577
Author(s):  
Ying-Hsien Huang ◽  
Feng-Sheng Wang ◽  
Pei-Wen Wang ◽  
Hung-Yu Lin ◽  
Sheng-Dean Luo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Heat Shock ◽  
Glucose Tolerance ◽  
Heat Shock Protein ◽  
Fatty Liver Disease ◽  
Heat Shock Protein 60 ◽  
Hepatic Inflammation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease ◽  
Tolerance Testing

Non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, consists of fat deposited (steatosis) in the liver due to causes besides excessive alcohol use. The folding activity of heat shock protein 60 (HSP60) has been shown to protect mitochondria from proteotoxicity under various types of stress. In this study, we investigated whether HSP60 could ameliorate experimental high-fat diet (HFD)-induced obesity and hepatitis and explored the potential mechanism in mice. The results uncovered that HSP60 gain not only alleviated HFD-induced body weight gain, fat accumulation, and hepatocellular steatosis, but also glucose tolerance and insulin resistance according to intraperitoneal glucose tolerance testing and insulin tolerance testing in HSP60 transgenic (HSP60Tg) compared to wild-type (WT) mice by HFD. Furthermore, overexpression of HSP60 in the HFD group resulted in inhibited release of mitochondrial dsRNA (mt-dsRNA) compared to WT mice. In addition, overexpression of HSP60 also inhibited the activation of toll-like receptor 3 (TLR3), melanoma differentiation-associated gene 5 (MDA5), and phosphorylated-interferon regulatory factor 3 (p-IRF3), as well as inflammatory biomarkers such as mRNA of il-1β and il-6 expression in the liver in response to HFD. The in vitro study also confirmed that the addition of HSP-60 mimics in HepG2 cells led to upregulated expression level of HSP60 and restricted release of mt-dsRNA, as well as downregulated expression levels of TLR3, MDA5, and pIRF3. This study provides novel insight into a hepatoprotective effect, whereby HSP60 inhibits the release of dsRNA to repress the TLR3/MDA5/pIRF3 pathway in the context of NAFLD or hepatic inflammation. Therefore, HSP60 may serve as a possible therapeutic target for improving NAFLD.

scholarly journals Addressing the liver progenitor cell response and hepatic oxidative stress in experimental non-alcoholic fatty liver disease/non-alcoholic steatohepatitis using amniotic epithelial cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mihiri Goonetilleke ◽  
Nathan Kuk ◽  
Jeanne Correia ◽  
Alex Hodge ◽  
Gregory Moore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Epithelial Cells ◽  
Fatty Liver ◽  
Progenitor Cells ◽  
Fatty Liver Disease ◽  
Hepatic Inflammation ◽  
Alcoholic Fatty Liver ◽  
And Oxidative Stress ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis. Human amniotic epithelial cells (hAECs) were previously shown to be beneficial in experimental models of chronic liver injury, reducing hepatic inflammation and fibrosis. Previous studies have shown that liver progenitor cells (LPCs) response plays a significant role in the development of fibrosis and HCC in mouse models of fatty liver disease. In this study, we examined the effect hAECs have on the LPC response and hepatic oxidative stress in an experimental model of NASH. Methods Experimental NASH was induced in C57BL/6 J male mice using a high-fat, high fructose diet for 42 weeks. Mice received either a single intraperitoneal injection of 2 × 106 hAECs at week 34 or an additional hAEC dose at week 38. Changes to the LPC response and oxidative stress regulators were measured. Results hAEC administration significantly reduced the expansion of LPCs and their mitogens, IL-6, IFNγ and TWEAK. hAEC administration also reduced neutrophil infiltration and myeloperoxidase production with a concurrent increase in heme oxygenase-1 production. These observations were accompanied by a significant increase in total levels of anti-fibrotic IFNβ in mice treated with a single dose of hAECs, which appeared to be independent of c-GAS-STING activation. Conclusions Expansion of liver progenitor cells, hepatic inflammation and oxidative stress associated with experimental NASH were attenuated by hAEC administration. Given that repeated doses did not significantly increase efficacy, future studies assessing the impact of dose escalation and/or timing of dose may provide insights into clinical translation.

Relationship between non-alcoholic fatty liver disease during pregnancy and abnormal glucose metabolism during and after pregnancy

2019 ◽  
Vol 68 (3) ◽  
pp. 743-747
Author(s):  
Maryam Sattari ◽  
Fernando Bril ◽  
Robert Egerman ◽  
Srilaxmi Kalavalapalli ◽  
Kenneth Cusi
Keyword(s):  
Diabetes Mellitus ◽  
Liver Disease ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Post Partum ◽  
Alcoholic Fatty Liver ◽  
Abnormal Glucose Metabolism ◽  
Alcoholic Fatty Liver Disease

While non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of impaired glucose tolerance and type 2 diabetes mellitus (DM) in non-pregnant patients, the clinical significance of NAFLD during pregnancy is still unclear. We hypothesized that sonographic findings of NAFLD during pregnancy would be associated with gestational diabetes mellitus (GDM) and predict abnormal postpartum glucose metabolism. NAFLD was assessed by ultrasound during and after pregnancy. Standard 2-hour 75 g oral glucose tolerance test (OGTT) was used during pregnancy and post partum to establish GDM and the diagnosis of normal, impaired fasting glucose, or DM. We also measured plasma insulin, C peptide, and free fatty acids (FFA) concentration during an OGTT to evaluate glucose tolerance, insulin secretion and insulin resistance. Of the 84 subjects, 12 had sonographic evidence of NAFLD (5 of whom had OGTT post partum). There was a non-significant trend toward higher mean weight and body mass index during and after gestation in the NAFLD group, but no statistically significant differences in mean age, ethnicity, prepregnancy and postpregnancy hemoglobin A1C values, and postpartum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, insulin, or FFA. We did not find an association between sonographic evidence of NAFLD during the third trimester of pregnancy and abnormal glucose metabolism during or after pregnancy. This study also suggests that while AST and ALT are not reliable diagnostic tools for NAFLD during the postpartum period, ultrasound is a reasonably safe, practical, and cost-effective modality to assess maternal hepatic fat during pregnancy.

500 Losartan Improves Hepatic Inflammation in Children With Non-Alcoholic Fatty Liver Disease

2016 ◽  
Vol 150 (4) ◽  
pp. S1036 ◽  
Author(s):  
Miriam Vos ◽  
Ran Jin ◽  
Jean Welsh ◽  
Juna Konomi ◽  
Saul J. Karpen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Hepatic Inflammation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Current management of non-alcoholic fatty liver disease

2016 ◽  
Vol 62 (9) ◽  
pp. 872-878 ◽  
Author(s):  
QUELSON COELHO LISBOA ◽  
SILVIA MARINHO FEROLLA COSTA ◽  
CLÁUDIA ALVES COUTO
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Modification ◽  
Hepatic Inflammation ◽  
Current Management ◽  
Multicenter Studies ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic inflammation and fibrosis. Lifestyle modification involving diet and enhanced physical activity associated with the treatment of underlying metabolic are the main stain in the current management of NAFLD. Insulin-sensitizing agents and antioxidants, especially thiazolidinediones and vitamin E, seem to be the most promising pharmacologic treatment for non-alcoholic steatohepatitis, but further long-term multicenter studies to assess safety are recommended.

Non‐alcoholic fatty liver disease is associated with cardiovascular disease in subjects with different glucose tolerance

2020 ◽  
Vol 36 (8) ◽  
Author(s):  
Teresa Vanessa Fiorentino ◽  
Elena Succurro ◽  
Angela Sciacqua ◽  
Francesco Andreozzi ◽  
Francesco Perticone ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Liver Disease ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease
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