scholarly journals Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
No-Joon Song ◽  
Ui Jeong Yun ◽  
Sunghee Yang ◽  
Chunyan Wu ◽  
Cho-Rong Seo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Acid Oxidation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

ZNF300 stimulates fatty acid oxidation and alleviates hepatosteatosis through regulating PPARα

2019 ◽  
Vol 476 (2) ◽  
pp. 385-404 ◽  
Author(s):  
Feng-Juan Yan ◽  
Yong-Jian Wang ◽  
Shi-Ran Yan ◽  
Jun Lu ◽  
Yuan-Lin Zheng
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Acid Oxidation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Underlying Mechanisms

Abstract ZNF300 plays an important role in the regulation of HBV-related hepatocellular carcinoma. However, little is known about the role of ZNF300 in lipid metabolism and NAFLD. In the present study, we observed that ZNF300 expression was markedly decreased in free fatty acid (FFA)-induced fatty liver. Overexpressed ZNF300 alleviated hepatic lipid accumulation, whereas knockdown of ZNF300 enhanced the FFA-induced lipid accumulation. Investigations of the underlying mechanisms revealed that ZNF300 directly binds to and regulates the PPARα expression, thus promoting fatty acid oxidation. Furthermore, bisulfite pyrosequencing PCR (BSP) analysis identified the hypermethylation status of ZNF300 gene in FFA-treated hepatocytes. Importantly, the suppression of ZNF300 could be blocked by DNA methyltransferase inhibitor (5-azadC) or DNMT3a-siRNA. These results suggested that ZNF300 plays an important role in hepatic lipid metabolism via PPARα promoting fatty acid oxidation and this effect might be blocked by DNMT3a-mediated methylation of ZNF300. Therefore, in addition to ZNF300 expression levels, the methylation status of this gene also has a potential as a prognostic biomarker.

scholarly journals Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet

2015 ◽  
Vol 113 (12) ◽  
pp. 1835-1843 ◽  
Author(s):  
Li Xu ◽  
Danping Huang ◽  
Qiaolin Hu ◽  
Jing Wu ◽  
Yizhen Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Basal Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Betaine Supplementation

To assess the effects of betaine on hepatic lipid accumulation and investigate the underlying mechanism, thirty-two male Sprague–Dawley rats weighing 100 (sd 2·50) g were divided into four groups, and started on one of four treatments: basal diet, basal diet with betaine administration, high-fat diet and high-fat diet with betaine administration. The results showed that no significant difference of body weight was found among experimental groups. Compared with high-fat diet-fed rats, a betaine supplementation decreased (P< 0·05) hepatic TAG accumulation induced by high-fat diet, which was also supported by hepatic histology results. Additionally, hepatic betaine–homocysteine methyltransferase activity as well as its mRNA abundance and lecithin level were found increased (P< 0·05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P< 0·05) activity of hepatic carnitine palmitoyltransferase 1 (CPT1) compared with high-fat diet-fed rats. High-fat diet inhibited (P< 0·05) the gene expression of hepatic PPARα and CPT1. However, betaine administration in high-fat diet-fed rats elevated (P< 0·05) the gene expression of PPARα and CPT1. Moreover, concentration, gene and protein expressions of hepatic fibroblast growth factor 21 (FGF21) were increased (P< 0·05) in response to betaine administration in high-fat diet group; meanwhile the gene expression of hepatic AMP-activated protein kinase was increased (P< 0·05) as well. The results suggest that betaine administration enhanced hepatic lipid export and fatty acid oxidation in high-fat diet-fed rats, thus effectively alleviating fat accumulation in the liver.

Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

2017 ◽  
Vol 316 ◽  
pp. 74-82 ◽  
Author(s):  
You-Jin Choi ◽  
Kang-Yo Lee ◽  
Seung-Hwan Jung ◽  
Hyung Sik Kim ◽  
Gayong Shim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Accumulation ◽  
Fatty Acid Translocase ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

scholarly journals MON-672 Progesterone Receptor Membrane Component 1 Suppresses Lipid Accumulation and Lipotoxicity in Animal Model of Diabetic Cardiomyopathy (DCM)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sang R Lee ◽  
Eui-ju Hong
Keyword(s):  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Mitochondrial Respiration ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Membrane Component

Abstract Diabetic cardiomyopathy (DCM) is one of the complications triggered by type II diabetes (T2D) (1). When free fatty acids (FFA) are abundant in insulin resistant pre-diabetic patients because of adipose lipolysis, FFA tends to move toward heart (2). Lipid accumulation can cause cardiac lipotoxicity and exacerbate DCM (3). In previous study, Pgrmc1 has been identified to associate with fatty acid synthesis (4). Therefore, we assumed that Pgrmc1 will associate with DCM. By feeding high-fat diet for 8 weeks and injecting streptozotocin (30mg/kg), T2D and DCM were induced. The lipid accumulation was exacerbated in T2D-induced Pgrmc1 KO heart, and FFA level was also high. Levels of lipid metabolic genes showed the tendency for lipid accumulation and lipotoxicity, and glycolysis was induced in T2D-induced Pgrmc1 KO heart. Though glycolysis presents higher efficiency for energy production in cardiomyopathy (5), it did not compensate the impairment of mitochondrial respiration in Pgrmc1 KO heart. High-fat diet and streptozotocin could not be the interfering factors, because suppression of fatty acid oxidation, induction of glycolysis, and impairment of mitochondrial respiration were observed similarly in post-prandial mice which were fed with normal chow. Insulin was excluded for interfering factor as cell line with serum starvation showed mitochondrial suppression and glycolytic induction in flux analyzer analysis in Pgrmc1 knockdown. Conversely, induction of fatty acid oxidation and suppression of glycolysis were observed in 72 h fasting of Pgrmc1 KO heart, suggesting the nutrition is closely associated with the metabolic modulation of Pgrmc1 on heart. This metabolic phenotype of Pgrmc1 KO heart consequently exacerbated DCM by showing high levels of fibrosis, inflammation, endoplasmic reticulum stress, and oxidative stress. References: (1) Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circulation research. 2018;122:624-38. (2) Noll C, Carpentier AC. Dietary fatty acid metabolism in prediabetes. Current opinion in lipidology. 2017;28:1-10. (3) Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell metabolism. 2012;15:805-12. (4) Lee SR, Kwon SW, Kaya P, Lee YH, Lee JG, Kim G, et al. Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis. Scientific reports. 2018;8:15711. (5) Nagoshi T, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S. Optimization of cardiac metabolism in heart failure. Current pharmaceutical design. 2011;17:3846-53.

Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes

2015 ◽  
Vol 18 (12) ◽  
pp. 1363-1370 ◽  
Author(s):  
Bonggi Lee ◽  
Misung Kwon ◽  
Jae Sue Choi ◽  
Hyoung Oh Jeong ◽  
Hae Young Chung ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Nelumbo Nucifera ◽  
Acid Oxidation

scholarly journals Hepatitis B Virus X Protein Induces Hepatic Steatosis by Enhancing the Expression of Liver Fatty Acid Binding Protein

2015 ◽  
Vol 90 (4) ◽  
pp. 1729-1740 ◽  
Author(s):  
Yun-li Wu ◽  
Xian-e Peng ◽  
Yi-bing Zhu ◽  
Xiao-li Yan ◽  
Wan-nan Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Transgenic Mice ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Fatty Acid Binding Protein ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Acid Binding Protein

ABSTRACTHepatitis B virus (HBV) has been implicated as a potential trigger of hepatic steatosis although molecular mechanisms involved in the pathogenesis of HBV-associated hepatic steatosis still remain elusive. Our prior work has revealed that the expression level of liver fatty acid binding protein 1 (FABP1), a key regulator of hepatic lipid metabolism, was elevated in HBV-producing hepatoma cells. In this study, the effects of HBV X protein (HBx) mediated FABP1 regulation on hepatic steatosis and the underlying mechanism were determined. mRNA and protein levels of FABP1 were measured by quantitative RT-PCR (qPCR) and Western blotting. HBx-mediated FABP1 regulation was evaluated by luciferase assay, coimmunoprecipitation, and chromatin immunoprecipitation. Hepatic lipid accumulation was measured by using Oil-Red-O staining and the triglyceride level. It was found that expression of FABP1 was increased in HBV-producing hepatoma cells, the sera of HBV-infected patients, and the sera and liver tissues of HBV-transgenic mice. Ectopic overexpression of HBx resulted in upregulation of FABP1 in HBx-expressing hepatoma cells, whereas HBx abolishment reduced FABP1 expression. Mechanistically, HBx activated the FABP1 promoter in an HNF3β-, C/EBPα-, and PPARα-dependent manner, in which HBx increased the gene expression of HNF3β and physically interacted with C/EBPα and PPARα. On the other hand, knockdown of FABP1 remarkably blocked lipid accumulation both in long-chain free fatty acids treated HBx-expressing HepG2 cells and in a high-fat diet-fed HBx-transgenic mice. Therefore, FABP1 is a key driver gene in HBx-induced hepatic lipid accumulation via regulation of HNF3β, C/EBPα, and PPARα. FABP1 may represent a novel target for treatment of HBV-associated hepatic steatosis.IMPORTANCEAccumulating evidence from epidemiological and experimental studies has indicated that chronic HBV infection is associated with hepatic steatosis. However, the molecular mechanism underlying HBV-induced pathogenesis of hepatic steatosis still remains to be elucidated. In this study, we found that expression of liver fatty acid binding protein (FABP1) was dramatically increased in the sera of HBV-infected patients and in both sera and liver tissues of HBV-transgenic mice. Forced expression of HBx led to FABP1 upregulation, whereas knockdown of FABP1 remarkably diminished lipid accumulation in bothin vitroandin vivomodels. It is possible that HBx promotes hepatic lipid accumulation through upregulating FABP1 in the development of HBV-induced nonalcoholic fatty liver disease. Therefore, inhibition of FABP1 might have therapeutic value in steatosis-associated chronic HBV infection.

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