scholarly journals Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3306
Author(s):  
Weiwei Zhu ◽  
Namood E Sahar ◽  
Hafiz Muhammad Ahmad Javaid ◽  
Eun Seon Pak ◽  
Guang Liang ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD.

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
Anna Virginia Adriana Pirozzi ◽  
Paola Imbimbo ◽  
Antonella D’Agostino ◽  
Virginia Tirino ◽  
Rosario Finamore ◽  
...  

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.


2019 ◽  
Vol 49 (9) ◽  
pp. 1214-1222 ◽  
Author(s):  
Elena Buzzetti ◽  
Andrew Hall ◽  
Mattias Ekstedt ◽  
Roberta Manuguerra ◽  
Marta Guerrero Misas ◽  
...  

2022 ◽  
Vol 8 ◽  
Author(s):  
Speranta Iacob ◽  
Susanne Beckebaum ◽  
Razvan Iacob ◽  
Cristian Gheorghe ◽  
Vito Cicinnati ◽  
...  

Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.


Author(s):  
Zeinab El Rashed ◽  
Hala Khalife ◽  
Adriana Voci ◽  
Elena Grasselli ◽  
Laura Canesi ◽  
...  

Non Alcoholic Fatty Liver Disease (NAFLD) is characterised by fat accumulation in hepatocytes in the form of triacyglycerols (TAGs) within cytosolic lipid droplets. Fucoidans (FUs) are biologically active polysaccharides usually isolated from brown marine algae, but recently identified also in terrestrial plants. In this study, we aimed to investigate the anti-oxidant and anti-steatotic effects of FUs purified from C. compressa, F. hermonis, and E. globulus. To this aim, we used a validated NAFLD in vitro model consisting of rat hepatoma FaO cells exposed to an oleate/palmitate mixture. Such a model is suitable for rapid investigation of direct effects of natural and artificial compounds, together with satisfying the strategy of 3Rs for laboratory use of animals. Our results indicated that all FUs display anti-oxidant and anti-steatotic activities. Steatotic FaO cells may be employed to further study the biological effects of FUs.


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