scholarly journals Light-to-Moderate Ethanol Feeding Augments AMPK-α Phosphorylation and Attenuates SREBP-1 Expression in the Liver of Rats

2013 ◽  
Vol 16 (2) ◽  
pp. 342 ◽  
Author(s):  
Srinivas Nammi ◽  
Basil D Roufogalis
Keyword(s):  
Liver Disease ◽  
Protein Expression ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Ethanol Consumption ◽  
Epidemiological Studies ◽  
Ethanol Treatment ◽  
Ethanol Feeding ◽  
Coa Reductase

Purpose: Fatty liver disease, a hepatic manifestation of metabolic syndrome, is one of the major causes of chronic liver diseases. Epidemiological studies suggest that regular light-to-moderate ethanol consumption lowers the risk of developing metabolic disorders including dislipidemia, insulin resistance, type 2 diabetes and fatty liver disease. However, the mechanism(s) of the protective effect of light-to-moderate ethanol consumption on the liver remains unknown. Methods: In the present study, we investigated the effects of light (6%, 0.94 g/kg/day) and moderate (12%, 1.88 g/kg/day) ethanol feeding in rats for 3 weeks on the circulating and hepatic biochemical profiles and on the hepatic protein expression and phosphorylation status of adenosine monophosphate-activated protein kinase-α (AMPK-α) and other down-stream targets of this enzyme including sterol regulatory element-binding protein-1 (SREBP-1), SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase). Results: Despite no significant difference in food-intake among the groups, light ethanol treatment significantly increased the body weight compared to control rats. Serum glucose, insulin, total cholesterol, triglycerides, phospholipids and hepatic cholesterol and triglycerides were not significantly different among the groups. However, serum free fatty acids were significantly reduced with light ethanol treatment. Both light and moderate ethanol treatment significantly increased the hepatic levels of phosphorylated AMPK-α protein and this was associated with significant reduction of SREBP-1 protein expression, suggesting an enhanced fatty acid oxidation. In addition, light ethanol treatment significantly decreased the SCAP protein expression in the liver. However, liver HMG-CoA protein expression was not significantly different with ethanol consumption. Conclusion: Chronic light-to-moderate ethanol consumption increased AMPK activation which was associated with decreased expression of SREBP-1 and SCAP in the liver. Thus, our studies provide mechanistic evidence for the earlier epidemiological studies that indicate light-to-moderate ethanol intake lowers the risk of development of fatty liver disease and other metabolic disorders. Our studies demonstrate that the protective effects of light-to-moderate ethanol arise at least in part by increased phosphorylation of AMPK-α and decreased SREBP-1 expression in the liver. Further studies are warranted to determine the effects of light-to-moderate ethanol on intracellular up-stream and down-stream targets of AMPK and also on the implications of light-to-moderate ethanol in protecting non-alcoholic fatty liver disease. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Prevalence and Risk Factors of Metabolic Associated Fatty Liver Disease in China: A Cross-Sectional Study

2021 ◽  
Author(s):  
Yuling Chen ◽  
Hao Li ◽  
Shu Li ◽  
Zhou Xu ◽  
Shen Tian ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Menopausal Status ◽  
Cross Sectional Study ◽  
Health Examination ◽  
Sectional Study ◽  
Cross Sectional

Abstract BackgroundMetabolic associated fatty liver disease (MAFLD) is a new definition for liver disease associated with known metabolic dysfunction. Based on new diagnostic criteria, we aim to investigate its prevalence and risk factors in Chinese.MethodsThis cross-sectional study was implemented on 139170 subjects who participated in health examination.Results Among 139170 subjects, prevalence of MAFLD was 26.1% (males: 35.4%; females: 14.1%), and it was significantly higher before 65-year-old in males than that in females (36.2% vs. 12.2%, P<0.001), however significantly lower after 65 (28.2% vs. 33.0%, P<0.001). The prevalence in different female menopausal status (premenopause, perimenopause, postmenopause) was 6.1%,16.8%, and 30.2%, in BMI groups (underweight, normal, overweight and obese), it was 0.1%, 4.0%, 27.4% and 59.8%. Proportions of abnormal metabolic features in MAFLD group were significantly higher than those in non-MAFLD group, so as the proportion of elevated alanine aminotransferase (ALT) (42.5% vs. 11%, P<0.001). Prevalence of metabolic syndrome (MS), dyslipidemia, and hyperuricemia in MAFLD group (53.2%, 80.0%, and 45.0%) was significantly higher than that in non-MAFLD group (10.1%, 41.7%, and 16.8%). Logistic regression revealed that age, BMI, waist circumference, ALT, triglyceride, fasting glucose, uric acid and platelet count were associated with MAFLD.ConclusionsMAFLD is prevalent in China, its prevalence varies among different groups of age, gender, BMI, and female menopausal status. MAFLD was related to metabolic disorders especially obesity. People with MAFLD suffer high prevalence of MS, dyslipidemia, hyperuricemia, and elevated liver enzymes. Metabolic disorders should be paid attention to improve management of MAFLD.

scholarly journals Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease

2019 ◽  
Vol 20 (9) ◽  
pp. 2215 ◽  
Author(s):  
Hamza El Hadi ◽  
Angelo Di Vincenzo ◽  
Roberto Vettor ◽  
Marco Rossato
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Current Understanding ◽  
Metabolic Complications ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Stroke Type ◽  
Alcoholic Fatty Liver Disease

With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.

Sulfated polysaccharides from Enteromorpha prolifera suppress SREBP-2 and HMG-CoA reductase expression and attenuate non-alcoholic fatty liver disease induced by a high-fat diet

2017 ◽  
Vol 8 (5) ◽  
pp. 1899-1904 ◽  
Author(s):  
Rendong Ren ◽  
Junjie Gong ◽  
Yanyan Zhao ◽  
Xinyun Zhuang ◽  
Yin Ye ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Sulfated Polysaccharides ◽  
Enteromorpha Prolifera ◽  
Hmg Coa Reductase ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Coa Reductase ◽  
Alcoholic Fatty Liver Disease

Enteromorpha prolifera polysaccharides (EP) suppressed SREBP-2 and regulates expression of HMG-CoA reductase. Therefore, EP may be a functional food that can prevent nonalcoholic fatty liver disease.

Effects of nonalcoholic fatty liver disease on the development of metabolic disorders

2007 ◽  
Vol 22 (7) ◽  
pp. 1086-1091 ◽  
Author(s):  
Jian-Gao Fan ◽  
Fen Li ◽  
Xiao-Bo Cai ◽  
Yong-De Peng ◽  
Qing-Hong Ao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Nonalcoholic Fatty Liver

scholarly journals Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ali Mahmoudi ◽  
Alexandra E. Butler ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Gene Ontology ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Biological Pathways ◽  
Venn Diagram ◽  
Nonalcoholic Fatty Liver

Background. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of liver damage, affecting ~25% of the global population. NAFLD comprises a spectrum of liver pathologies, from hepatic steatosis to nonalcoholic steatohepatitis (NASH), and may progress to liver fibrosis and cirrhosis. The presence of NAFLD correlates with metabolic disorders such as hyperlipidemia, obesity, blood hypertension, cardiovascular, and insulin resistance. Fenofibrate is an agonist drug for peroxisome proliferator-activated receptor alpha (PPARα), used principally for treatment of hyperlipidemia. However, fenofibrate has recently been investigated in clinical trials for treatment of other metabolic disorders such as diabetes, cardiovascular disease, and NAFLD. The evidence to date indicates that fenofibrate could improve NAFLD. While PPARα is considered to be the main target of fenofibrate, fenofibrate may exert its effect through impact on other genes and pathways thereby alleviating, and possibly reversing, NAFLD. In this study, using bioinformatics tools and gene-drug, gene-diseases databases, we sought to explore possible targets, interactions, and pathways involved in fenofibrate and NAFLD. Methods. We first determined significant protein interactions with fenofibrate in the STITCH database with high confidence (0.7). Next, we investigated the identified proteins on curated targets in two databases, including the DisGeNET and DISEASES databases, to determine their association with NAFLD. We finally constructed a Venn diagram for these two collections (curated genes-NAFLD and fenofibrate-STITCH) to uncover possible primary targets of fenofibrate. Then, Gene Ontology (GO) and KEGG were analyzed to detect the significantly involved targets in molecular function, biological process, cellular component, and biological pathways. A P value < 0.01 was considered the cut-off criterion. We also estimated the specificity of targets with NAFLD by investigating them in disease-gene associations (STRING) and EnrichR (DisGeNET). Finally, we verified our findings in the scientific literature. Results. We constructed two collections, one with 80 protein-drug interactions and the other with 95 genes associated with NAFLD. Using the Venn diagram, we identified 11 significant targets including LEP, SIRT1, ADIPOQ, PPARA, SREBF1, LDLR, GSTP1, VLDLR, SCARB1, MMP1, and APOC3 and then evaluated their biological pathways. Based on Gene Ontology, most of the targets are involved in lipid metabolism, and KEGG enrichment pathways showed the PPAR signaling pathway, AMPK signaling pathway, and NAFLD as the most significant pathways. The interrogation of those targets on authentic disease databases showed they were more specific to both steatosis and steatohepatitis liver injury than to any other diseases in these databases. Finally, we identified three significant genes, APOC3, PPARA, and SREBF1, that showed robust drug interaction with fenofibrate. Conclusion. Fenofibrate may exert its effect directly or indirectly, via modulation of several key targets and pathways, in the treatment of NAFLD.

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