scholarly journals NEFA-Sensitive Orai1 Expression in Regulation of De Novo Lipogenesis

2018 ◽  
Vol 47 (3) ◽  
pp. 1310-1317 ◽  
Author(s):  
Bingbing Zhang ◽  
Wei Yang ◽  
Ying Zou ◽  
Ming Li ◽  
Han Guo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Western Blot ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Inflammatory Responses ◽  
Quantitative Polymerase Chain Reaction ◽  
Lipid Synthesis ◽  
De Novo Lipogenesis ◽  
Synthesis Methods ◽  
Alcoholic Fatty Liver

Background/Aims: Non-esterified fatty acids (NEFAs) are important inducers of inflammatory responses and hepatic lipid accumulation, which lead to non-alcoholic fatty liver disease (NAFLD). High plasma NEFA is found in NAFLD patients, and associated with metabolic syndrome and type-2 diabetes. NFκB is known to upregulate Orai1, the Ca2+ channel responsible for store-operated Ca2+ entry. The present study explored the role of NEFA-sensitive NFκB-dependent Orai1 expression in the regulation of lipid synthesis. Methods: BRL-3A rat liver hepatocyte lines were studied in the absence and presence of NEFA. Transcript and protein expression levels of factors involved in lipid synthesis were quantified by quantitative polymerase chain reaction (qPCR) and western blot analyses. Fatty acids were measured by immunofluorescence. Results: NEFA significantly increased, as indicated by the expression of sterol regulatory element-binding protein 1 (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase α (ACC1), Orai1, and NFκB p65 by qPCR and western blot analyses. These effects were reversed by the Orai1 inhibitor, 2-aminoethoxydiphenyl borate, and the NFκB inhibitor, wogonin. Furthermore, SREBP-1c, FAS, ACC1, and Orai1 were significantly decreased by Orai1 silencing. Conclusions: Taken together, these results demonstrated that NEFA-sensitive NFκB-dependent Orai1 expression regulates de novo lipogenesis.

scholarly journals β-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Zhe Gao ◽  
Guang-Yao Song ◽  
Lu-Ping Ren ◽  
Hui-Juan Ma ◽  
Bo-Qing Ma ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Receptor Agonist ◽  
Nuclear Translocation ◽  
De Novo ◽  
Lipid Synthesis ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
High Fructose ◽  
Alcoholic Fatty Liver Disease

The hypoglycemic drug GLP-1 receptor agonist can ameliorate hepatic steatosis but the mechanism is not clear. Intake of high fructose leads to non-alcoholic fatty liver disease by stimulating lipid synthesis, and β-catenin is the key molecule for realizing GLP-1 function in extrahepatic tissues; with the discovery of GLP-1 receptor in liver, we speculate that β-catenin might mediate GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose. Wistar rats were fed with high fructose diet for 8 weeks and then treated with GLP-1 receptor agonist exenatide for 4 weeks; the changes of lipid synthesis pathway factors, the expression and nuclear translocation of β-catenin, and the hepatic steatosis of the rats were observed. After the intervention of exenatide, the hepatic steatosis induced by high fructose was improved, the nuclear translocation and expression of β-catenin were facilitated, and the mRNA and protein expression of the upstream regulator SREBP-1 and the downstream key enzymes ACC, FAS and SCD-1 of de novo lipogenesis were down-regulated. GLP-1 receptor agonist may ameliorate hepatic steatosis induced by high fructose by β-catenin regulating de novo lipogenesis pathway. GLP-1 receptor agonist may be a potential new drug for the treatment of non-alcoholic fatty liver disease, and the β-catenin may be an important target for the drug therapy.

scholarly journals Allopurinol Prevents the Lipogenic Response Induced by an Acute Oral Fructose Challenge in Short-Term Fructose Fed Rats

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 601 ◽  
Author(s):  
García-Arroyo ◽  
Monroy-Sánchez ◽  
Muñoz-Jiménez ◽  
Gonzaga ◽  
Andrés-Hernando ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Tap Water ◽  
De Novo Lipogenesis ◽  
Sprague Dawley ◽  
Short Term ◽  
Alcoholic Fatty Liver ◽  
High Fructose

We investigated whether short term high fructose intake may induce early hepatic dysfunction in rats and to test whether allopurinol treatment may have beneficial effects. Twenty male Sprague-Dawley rats received 20% fructose in drinking water (10 treated with allopurinol and 10 received vehicle) and 10 control rats received tap water. After 14 days, the hepatic response to an acute fructose load was evaluated, and in fasted animals, respirometry studies in freshly isolated mitochondria were performed. In fasting rats, we did not find differences in systemic or hepatic uric acid and triglyceride concentrations among the groups, but mitochondrial respiratory control rate was significantly decreased by high fructose feeding and correlated with a reduced expression of Complex I, as well as decreased aconitase-2 activity. On the other hand, in fructose fed rats, an acute fructose load increased systemic and hepatic uric acid, triglycerides and oxidative stress. Fructose feeding was also associated with fructokinase and xanthine oxidase overexpression and increased liver de novo lipogenesis program (fatty acid synthase (FAS) and cell death-inducing DFFA-like effector C (CIDEC) overexpression, ATP citrate lyase (ACL) and acetyl coA carboxylase (ACC) overactivity and decreased AMP-activated protein kinase (AMPk) and endothelial nitric oxide synthase (eNOS) activation). Allopurinol treatment prevented hepatic and systemic alterations. These data suggest that early treatment with xanthine oxidase inhibitors might provide a therapeutic advantage by delaying or even halting the progression of non-alcoholic fatty liver disease (NAFLD).

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