Dietary Nicotinic Acid Supplementation Ameliorates Chronic Alcohol-Induced Fatty Liver in Rats

Li, Qiong; Xie, Guoxiang; Zhang, Wenliang; Zhong, Wei; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Wang, Jia; Zhou, Zhanxiang

doi:10.1111/acer.12396

Cited by 36 publications

(29 citation statements)

References 40 publications

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“…Moreover, we measured the ratio of NAD+/NADH after alcohol exposure with or without GKT137831 treatment for the last two weeks. It is well known that decrease NAD+/NADH ratio favoring lipid accumulation 39 . In the current study, GKT137831 did not restore the ratio of NAD+/NADH.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of NOX4 ameliorates alcohol-induced liver injury in mice through improving oxidative stress and mitochondrial function

Sun

Zhang

Zhong

et al. 2017

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background-Oxidative stress plays a crucial role in the development of alcoholic liver disease (ALD), however effective pharmacological treatments for oxidative injury is still lacking. The objective of this study was to determine whether inhibition of NADPH oxidase activity could reverse alcohol-induced liver injury via protecting mitochondrial functions.Methods-C57BL/6J mice were pair-fed with Lieber-DeCarli control or ethanol diet for four week with or without administration with 30mg/kg/d GKT137831, a NOX4 inhibitor for the last two weeks. H4IIEC3 cells were transfected with scrambled or NOX4 shRNA. Cells were then treated with 200mM ethanol for 48h.Results-Alcohol exposure induced NOX4 expression in the liver and mitochondrial fraction. GKT137831 partially reversed alcohol-induced liver injury and elevation of serum H 2 O 2 . The levels of mitochondrial ROS, mitochondrial DNA, respiratory chain complex IV, and hepatic ATP were partially reversed by GKT137831 after alcohol exposure. Furthermore GKT137831 ameliorated alcohol-induced lipid accumulation and increased HNF-4α and β-oxidation enzymes. GKT137831 also decreased alcohol-induced apoptosis coupled with decreased insertion of Bax into mitochondria and decreased activation of cleaved caspase-9 and cleaved PARP. Mechanistic study shows that ethanol induced expression of NOX4 in H4IIEC3 cells. Knockdown of NOX4 caused an increased mitochondrial membrane potential, decreased mitochondrial superoxide levels, reduced number of apoptotic cells, decreased lipid accumulation, and improved ATP levels and NAD+/NADH ratio after ethanol treatment.

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Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of NOX4 ameliorates alcohol-induced liver injury in mice through improving oxidative stress and mitochondrial function

Sun

Zhang

Zhong

et al. 2017

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…161 Studies by our group showed that niacin increases hepatic fatty acid oxidation and decreases de novo lipogenesis in rats. 164 Dietary supplementation with niacin also reversed alcoholic endotoxemia, and upregulated the expression of tight junction proteins, especially claudins. 83 Interestingly, niacin significantly lowered endotoxin and acetaldehyde levels in the intestinal lumen, which indicates a direct impact of niacin on gut microbiota.…”

Section: Targeting the Leaking Gut To Treat Aldmentioning

confidence: 98%

Targeting the gut barrier for the treatment of alcoholic liver disease

Zhou

Zhong

2017

Liver Research

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Alcohol consumption remains one of the predominant causes of liver disease and liver-related death worldwide. Intriguingly, dysregulation of the gut barrier is a key factor promoting the pathogenesis of alcoholic liver disease (ALD). A functional gut barrier, which consists of a mucus layer, an intact epithelial monolayer and mucosal immune cells, supports nutrient absorption and prevents bacterial penetration. Compromised gut barrier function is associated with the progression of ALD. Indeed, alcohol consumption disrupts the gut barrier, increases gut permeability, and induces bacterial translocation both in ALD patients and in experimental models with ALD. Moreover, alcohol consumption also causes enteric dysbiosis with both numerical and proportional perturbations. Here, we review and discuss mechanisms of alcohol-induced gut barrier dysfunction to better understand the contribution of the gut-liver axis to the pathogenesis of ALD. Unfortunately, there is no effectual Food and Drug Administration-approved treatment for any stage of ALD. Therefore, we conclude with a discussion of potential strategies aimed at restoring the gut barrier in ALD. The principle behind antibiotics, prebiotics, probiotics and fecal microbiota transplants is to restore microbial symbiosis and subsequently gut barrier function. Nutrient-based treatments, such as dietary supplementation with zinc, niacin or fatty acids, have been shown to regulate tight junction expression, reduce intestinal inflammation, and prevent endotoxemia as well as liver injury caused by alcohol in experimental settings. Interestingly, saturated fatty acids may also directly control the gut microbiome. In summary, clinical and experimental studies highlight the significance and efficacy of the gut barrier in treating ALD.

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“…In addition, chronic alcohol consumption interferes with the one-carbon (1C) metabolism and causes disruption of DNA methylation by inhibiting methionine synthase, an enzyme that converts homocysteine to methionine and leads to signicant reduction in S-adenosyl methionine (SAM) levels, thereby contributing to DNA hypomethylation. 90 Uncontrolled clinical studies have suggested that niacin therapy signicantly reduces the risk of cardiovascular events in high risk subjects. Two clinical trials failed to conrm this benet except for familial hypercholesterolemia resistance to statin.…”

Section: Nad Deficienciesmentioning

confidence: 99%

“…This is an explored pathway to reduce the use of antibiotics in the poultry business. [88][89][90] Likewise transgenic fruits overproducing PPs are sought aer.…”

Section: Nad Deficienciesmentioning

confidence: 99%

Can we use the epigenetic bioactivity of caloric restriction and phytochemicals to promote healthy ageing?

Christodoulou

Thomas

Poulain³

et al. 2014

Med. Chem. Commun.

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In 2011, the Centers for Disease Control and Prevention reported that half of Americans are using food supplements, intended to provide them with nutrients that they believe they consume in insufficient quantities. Dietary supplements were repeatedly said to be unnecessary if one eats a balanced diet but within the booming "silver economy", sales of vitamins, minerals and supplements totalled nearly $23 billion in the US last year (Euro monitor International). Seventy eight "antioxidant" supplements trials including 296 707 participants were reviewed by the Cochrane Database System Review. It was concluded that beta-carotene and vitamin E supplements, instead of promoting longevity, were increasing mortality and so may high doses of vitamin A. Several nutrition interventions with or without edible phytochemicals, fasting regimens, and food supplements have now been tried to prevent the development of many different types of tumors. Most were known as antioxidants and are now repurposed because they were shown to change the epigenome. Epigenetic marks are enzymatic tags deposited on the genome which do not change the DNA sequence but change gene expression. They are reversible and epigenetic dietary interventions are thus suggested for the prevention of ageing, ageing related diseases and for breaking the vicious circle of the trans-generational epigenetic inheritance of the metabolic disorders. It is a pressing issue because more and more children are exposed to parents' obesity and are at risk of developing type 2 diabetes. Why is it relevant to propose epigenetic "Nutricures" to prevent diseases linked with ageing? To answer this question we produce this review, whose scope is to underline the importance of the nutritional contribution for a correct functioning of epigenetics. Almost all chromatin-modifying enzymes utilize co-factors, which are crucial metabolites for core metabolism pathways. Because the cellular concentrations of these metabolites fluctuate as a function of the metabolic status of the cell, the activity of most epigenetic enzymes depends on the cell metabolism and thus nutrition. Through one selected representative example, sirtuins, and their metabolic co-factor, nicotinamide, we illustrate the nutrition and epigenetic connections. Then we describe the epigenetic activities of some polyphenols. Finally we underline that with globalization there is a continuing trend changing the variety of food items that we consume. Each may have bioactive effects that may combine with additional epigenetic effects of pollutants such as pesticides. We plead likewise that because they are bioactive, "Nutricures" and food supplements should undergo better evaluation before marketing.

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Dietary Nicotinic Acid Supplementation Ameliorates Chronic Alcohol-Induced Fatty Liver in Rats

Cited by 36 publications

References 40 publications

Pharmacological inhibition of NOX4 ameliorates alcohol-induced liver injury in mice through improving oxidative stress and mitochondrial function

Pharmacological inhibition of NOX4 ameliorates alcohol-induced liver injury in mice through improving oxidative stress and mitochondrial function

Targeting the gut barrier for the treatment of alcoholic liver disease

Can we use the epigenetic bioactivity of caloric restriction and phytochemicals to promote healthy ageing?

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