scholarly journals Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

2022 ◽  
Vol 23 (1) ◽  
pp. 498
Author(s):  
João Paulo Margiotti dos Santos ◽  
Mariana Canevari de Maio ◽  
Monike Alves Lemes ◽  
Lucas Fornari Laurindo ◽  
Jesselina Francisco dos Santos Haber ◽  
...  

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. In this sense, this study aimed to perform a review of the role of organokines in NASH. Thus, by combining descriptors such as NASH, organokines, oxidative stress, inflammation, insulin resistance, and dyslipidemia, a search was carried out in the EMBASE, MEDLINE-PubMed, and Cochrane databases of articles published in the last ten years. Insulin resistance, inflammation and mitochondrial dysfunction, fructose, and intestinal microbiota were factors identified as participating in the genesis and progression of NASH. Changes in the pattern of organokines secretion (adipokines, myokines, hepatokines, and osteokines) directly or indirectly contribute to aggravating the condition or compromise homeostasis. Thus, further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.

2013 ◽  
Vol 144 (5) ◽  
pp. S-1013
Author(s):  
Billur Canbakan ◽  
Hakan Senturk ◽  
Murat Tuncer ◽  
Ibrahim Hatemi ◽  
Emine Koroglu ◽  
...  

Author(s):  
Pallavi M. ◽  
Suchitra M. M. ◽  
Alok Sachan ◽  
Lakshmi A. Y. ◽  
Srinivasa Rao P. V. L. N.

Background: Type 2 diabetes mellitus (T2DM) is associated with chronic inflammation and oxidative stress, implicated in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Present study aimed to assess the role of adipokines, oxidative stress, and endotoxins in the pathogenesis of NAFLD in T2DM.Methods: Present cross-sectional observational study included healthy controls (n=50; group 1); T2DM patients without NAFLD (n=50; group 2), T2DM patients with NAFLD (n=50; group 3). Study subjects were age and gender matched.Results: Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high sensitive C-reactive protein (hs-CRP), endotoxin, malondialdehyde (MDA) were significantly elevated and adiponectin, ferric reducing ability of plasma (FRAP), and glutathione (GSH) were significantly lower (p<0.001) in T2DM patients with NAFLD when compared to T2DM patients without NAFLD and controls. Endotoxin showed significant positive correlation with TNF-α (r=0.304; p<0.001), hs-CRP (r=0.193; p=0.018), and MDA (r=0.420; p<0.001), and significant negative correlation with adiponectin (r=-0.406; p<0.001). TNF-α and IL-6 showed significant positive correlation with MDA (r=0.526; p<0.001, r=0.229; p=0.005) and significant negative correlation with adiponectin (r=-0.396; p<0.001, r=-0.318; p<0.001), FRAP (r=-0.418; p<00.001, r=-0.170; p=0.038), and GSH (r=-0.353; p<0.001, r=-0.301; p<0.001).Conclusions: Authors observed elevated endotoxin, oxidative stress, inflammation and lower adiponectin levels in T2DM subjects compared to controls. These changes were more pronounced in T2DM with NAFLD when compared to T2DM without NAFLD.  Lower adiponectin levels were found to be a better predictor of NALFD in T2DM and is associated with oxidative stress and systemic inflammation.


2016 ◽  
Vol 27 (4) ◽  
pp. 361-366 ◽  
Author(s):  
Emine Koroglu ◽  
Billur Canbakan ◽  
Kadri Atay ◽  
Ibrahim Hatemi ◽  
Murat Tuncer ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 184
Author(s):  
Daryl Ramai ◽  
Waqqas Tai ◽  
Michelle Rivera ◽  
Antonio Facciorusso ◽  
Nicola Tartaglia ◽  
...  

Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a “multi-hit” or “multi-parallel hit” model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.


2013 ◽  
Vol 41 (03) ◽  
pp. 487-502 ◽  
Author(s):  
Wei-Xi Cui ◽  
Jie Yang ◽  
Xiao-Qing Chen ◽  
Qian Mao ◽  
Xiang-Lan Wei ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) has become a major challenge to the healthcare system. This study was designed to evaluate the effect of the triterpenoid-rich fraction (TF) from Ilex hainanensis Merr. on NAFLD. Male Sprague-Dawley (SD) rats were fed a normal diet (control) or high fat diet (NAFLD model). After four weeks, the high fat diet group was orally administrated TF (250 mg/kg) for another two weeks. High fat diet fed rats displayed hyperlipidemia and a decline in liver function compared with control. However, administration with TF could effectively improve these symptoms, as demonstrated by decreasing the plasma levels of triglyceride (p <0.05), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), alanine transaminase (p < 0.05), aspartate aminotransferase (p < 0.01), liver index (p < 0.05) and insulin resistance index (p < 0.05) while increasing the high-density lipoprotein cholesterol (p < 0.05). Meanwhile, histopathological examination of livers also showed that TF could reduce the incidence of liver lesions induced by high fat diet. Furthermore, TF could alleviate oxidative stress and inflammation status indicated by the decline malondialdehyde and superoxide dismutase levels (p < 0.01, both) and levels of interleukin 6 and tumor necrosis factor-α (p < 0.05). In addition, immunohistochemistry showed TF evidently elevated the peroxisome proliferator-activated receptor (PPARα) expression (p < 0.01), while it diminished the Cytochrome P450 2E1 (CYP2E1) expression (p < 0.01) in liver. These results demonstrate that TF has potential ability to protect liver against NAFLD by regulating lipids metabolism and alleviating insulin resistance, inflammation and oxidative stress. This effect might be associated with regulating PPARα and CYP2E1 expression.


2020 ◽  
Vol 183 (11) ◽  
pp. 51-61
Author(s):  
N. N. Vlasov ◽  
E. A. Kornienko

There is ample evidence that insulin resistance, hyperinsulinemia, and obesity are at the heart of the development of non-alcoholic fatty liver disease (NAFLD). The disease is now considered as the hepatic component of metabolic syndrome (MS).64 children with NAFLD were assessed for metabolic syndrome stigma. An analysis was also made on the state of the problem according to the literature on the general links of the pathogenesis of these conditions, methods of diagnosis and treatment of NAFLD.All components of MS are observed with different frequencies in patients with NAFD. This disease, together with type 2 diabetes mellitus, becomes very common diseases in childhood. The incidence of NAFLD in children is constantly growing, it has begun to occur in infants, an outcome in cirrhosis of the liver is possible within childhood, although the prognosis for NAFLD remains definitely uncertain. Weight loss with a low glycemic index diet, regular exercise, and other lifestyle changes are the mainstay of NAFLD treatment, but not yet very effective for various reasons. In these conditions, it is necessary to increase the role of primary prevention of MS and NAFLD.


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