ABSTRACT
BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including PPARγ, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.
Subject(s)
Acetylation , Dietary Supplements , Epigenomics , Hep G2 Cells , Histone Acetyltransferases , Histones , Lipid Metabolism , Lipogenesis , Liver , Lysine , Metabolic Diseases , Non-alcoholic Fatty Liver Disease , RNA, Messenger , Sterol Regulatory Element Binding Protein 1ABSTRACT
BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.
Subject(s)
Animals , Mice , Allium , Body Weight , Diet , Diet, Western , Drug Combinations , Ethanol , Hep G2 Cells , Hepatocytes , In Vitro Techniques , Lipogenesis , Liver , Liver Diseases , Mice, Obese , Non-alcoholic Fatty Liver Disease , Oleic Acid , Sterol Regulatory Element Binding Protein 1 , Transcriptional ActivationABSTRACT
Extracorporeal membrane oxygenation (ECMO) is a life-sustaining salvage therapy applied to the patient with acute heart failure or respiratory failure which is considered curable, but uncorrectable by conventional means. Recently, accumulating data has shown the survival benefit of ECMO in patients with acute fatal cardiopulmonary decompensation. Here, we report a series of cases of successful ECMO treatment in patients with acute cardiopulmonary insufficiency. Case 1: A patient with progressive respiratory failure on mechanical ventilation after pneumonectomy was managed satisfactorily using a veno-venous ECMO. Case 2: A veno-arterial ECMO was used to support a patient with vasopressor refractory septic shock. After 5 days of treatment, the patient was successfully weaned from ECMO. Case 3: A patient in cardiac arrest after the orthopedic surgery was resuscitated using a veno-arterial ECMO. Pulmonary angiography on ECMO revealed massive pulmonary thromboembolism and embolectomy was thoroughly performed under the support of ECMO.
Subject(s)
Humans , Angiography , Embolectomy , Extracorporeal Membrane Oxygenation , Heart Arrest , Heart Failure , Intensive Care Units , Critical Care , Orthopedics , Pneumonectomy , Pulmonary Embolism , Respiration, Artificial , Respiratory Insufficiency , Salvage Therapy , Shock, SepticABSTRACT
We have investigated the function and mechanisms of the CARM1-SNF5 complex in T3-dependent transcriptional activation. Using specific small interfering RNAs (siRNA) to knock down coactivators in HeLa alpha2 cells, we found that coactivator associated arginine methyltransferase 1 (CARM1) and SWI/SNF complex component 5 (SNF5) are important for T3-dependent transcriptional activation. The CARM1- SWI/SNF chromatin remodeling complex serves as a mechanism for the rapid reversal of H3-K9 methylation. Importantly, siRNA treatment against CARM1 and/or SNF5 increased the recruitment of HMTase G9a to the type 1 deiodinase (D1) promoter even with T3. Knocking- down either CARM1 or SNF5 also inhibited the down- regulation of histone macroH2A, which is correlated with transcriptional activation. Finally, knocking down CARM1 and SNF5 by siRNA impaired the association of these coactivators to the D1 promoter, suggesting functional importance of CARM1- SNF5 complex in T3-dependent transcriptional activation.