scholarly journals The Impact of Obesity and Metabolic Syndrome on Alcoholic Liver Disease

2014 ◽  
Vol 18 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Dian J. Chiang ◽  
Arthur J. McCullough
2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Mohammed A. Assiri ◽  
Hadi R. Ali ◽  
John O. Marentette ◽  
Youngho Yun ◽  
Juan Liu ◽  
...  

Abstract Background Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD+/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD+ levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD+ boosting supplement to investigate alterations in the pathogenesis of early-stage ALD. Methods To examine the impact of NAD+ therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis. Results Our findings reveal that NMN therapy increased hepatic NAD+ levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression. Conclusions These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD+-based interventions.


2015 ◽  
Vol 10 (2) ◽  
pp. 347-354 ◽  
Author(s):  
Waleed Al-hamoudi ◽  
Faisal Abaalkhail ◽  
Abdurahman Bendahmash ◽  
Naglaa Allam ◽  
Bassem Hegab ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Catalina Fuenzalida ◽  
María Soledad Dufeu ◽  
Jaime Poniachik ◽  
Juan Pablo Roblero ◽  
Lucía Valenzuela-Pérez ◽  
...  

Alcoholic liver disease (ALD) is one of the leading causes of morbidity among adults with alcohol use disorder (AUD) worldwide. Its clinical course ranges from steatosis to alcoholic hepatitis, progressing to more severe forms of liver damage, such as cirrhosis and hepatocellular carcinoma. The pathogenesis of ALD is complex and diverse elements are involved in its development, including environmental factors, genetic predisposition, the immune response, and the gut-liver axis interaction. Chronic alcohol consumption induces changes in gut microbiota that are associated with a loss of intestinal barrier function and inflammatory responses which reinforce a liver damage progression triggered by alcohol. Alcohol metabolites such as acetaldehyde, lipid peroxidation-derived aldehyde malondialdehyde (MDA), and protein-adducts act as liver-damaging hepatotoxins and potentiate systemic inflammation. Additionally, ethanol causes direct damage to the central nervous system (CNS) by crossing the blood-brain barrier (BBB), provoking oxidative stress contributing to neuroinflammation. Overall, these processes have been associated with susceptibility to depression, anxiety, and alcohol craving in ALD. Recent evidence has shown that probiotics can reverse alcohol-induced changes of the microbiota and prevent ALD progression by restoring gut microbial composition. However, the impact of probiotics on alcohol consumption behavior has been less explored. Probiotics have been used to treat various conditions by restoring microbiota and decreasing systemic and CNS inflammation. The results of some studies suggest that probiotics might improve mental function in Alzheimer’s, autism spectrum disorder, and attenuated morphine analgesic tolerance. In this sense, it has been observed that gut microbiota composition alterations, as well as its modulation using probiotics, elicit changes in neurotransmitter signals in the brain, especially in the dopamine reward circuit. Consequently, it is not difficult to imagine that a probiotics-based complementary treatment to ALD might reduce disease progression mediated by lower alcohol consumption. This review aims to present an update of the pathophysiologic mechanism underlying the microbiota-gut-liver-brain axis in ALD, as well as to provide evidence supporting probiotic use as a complementary therapy to address alcohol consumption disorder and its consequences on liver damage.


2021 ◽  
Vol 32 (8) ◽  
pp. 661-666
Author(s):  
Haluk Tarik Kani ◽  
◽  
Coskun Ozer Demirtas ◽  
Caglayan Keklikkiran ◽  
Ilkay Ergenc ◽  
...  

2014 ◽  
Vol 146 (5) ◽  
pp. S-984
Author(s):  
Mohamed G. Shoreibah ◽  
Evan Raff ◽  
Donny D. Kakati ◽  
Joseph R. Bloomer ◽  
Ashwani K. Singal

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