scholarly journals Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH

2021 ◽  
Vol 46 ◽  
pp. 101178
Author(s):  
Leigh Goedeke ◽  
Gerald I. Shulman
2018 ◽  
Vol 28 (4) ◽  
pp. 955-961 ◽  
Author(s):  
Samaneh Goorani ◽  
Mohsen Zhaleh ◽  
Mohammad Kazem Koohi ◽  
Niloofar Seydi ◽  
Khodabakhsh Rashidi ◽  
...  

2011 ◽  
Vol 30 (1) ◽  
pp. 6-19 ◽  
Author(s):  
Haim Shapiro ◽  
Miryam Tehilla ◽  
Joelle Attal-Singer ◽  
Rafael Bruck ◽  
Rachel Luzzatti ◽  
...  

2014 ◽  
Vol 23 (3) ◽  
pp. 311-319 ◽  
Author(s):  
Yasar Colak ◽  
Atakan Yesil ◽  
Hasan Huseyin Mutlu ◽  
Ozge Telci Caklili ◽  
Celal Ulasoglu ◽  
...  

Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its antiinflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there are no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.


2019 ◽  
Vol 847 ◽  
pp. 72-82 ◽  
Author(s):  
Marwa B. Bakir ◽  
Mona A. Salama ◽  
Rowaida Refaat ◽  
Mennatallah A. Ali ◽  
Eman A. Khalifa ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172900 ◽  
Author(s):  
María Eugenia Inzaugarat ◽  
Elena De Matteo ◽  
Placida Baz ◽  
Diego Lucero ◽  
Cecilia Claudia García ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 872 ◽  
Author(s):  
Jinchunzi Yang ◽  
Marta Fernández-Galilea ◽  
Leyre Martínez-Fernández ◽  
Pedro González-Muniesa ◽  
Adriana Pérez-Chávez ◽  
...  

Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.


2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Mandeep K. Arora ◽  
Sudhanshu Pandey ◽  
Ritu Tomar ◽  
Jagannath Sahoo ◽  
Dinesh Kumar ◽  
...  

Abstract Background High-fat diet (HFD) possesses a major cause of cardiovascular disease, and hepatosteatosis. Unfortunately, long-term use of statins has a theoretical possibility of worsening of hepatic histology in the patients with non-alcoholic fatty liver disease (NAFLD). The objective of the study was to explore hepatoprotective potential of policosanol as an alternative to statins in experimental NAFLD. For the same, young male Wistar rats were fed with HFD for 8 weeks to induce NAFLD. 48 adult Wistar rats were distributed into six investigational groups: normal control, HFD control, and four treatment groups, receiving policosanol (50 and 100 mg/kg/day), atorvastatin (30 mg/kg/day), and silymarin (100 mg/kg/day) for 8 weeks along with HFD. Result HFD consumption caused profound hepatotoxicity evident by hepatic oxidative stress, increased Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), Alkaline phosphatase (ALP), and bilirubin content. Treatment with policosanol (100 mg/kg) markedly reduced the elevated SGOT, SGPT, and ALP levels in HFD-fed rats. Moreover, policosanol significantly reduced hepatic oxidative stress manifest by reduced malondialdehyde (MDA) and increased glutathione (GSH) level. The treatment with policosanol (100 mg/kg) was found to be more active in attenuating the HFD-induced hepatotoxicity as compared to policosanol (50 mg/kg) and atorvastatin (30 mg/kg). Moreover, we observed that the hepatoprotective potential of policosanol was comparable to the silymarin. Conclusions The results of the study clearly indicated that the policosanol could be considered an intriguing approach for the treatment of NAFLD.


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