scholarly journals Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhang-Hong Ke ◽  
Jie-Xue Pan ◽  
Lu-Yang Jin ◽  
Hai-Yan Xu ◽  
Tian-Tian Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lipid Metabolism ◽  
Bisphenol A ◽  
Lipid Accumulation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Methylation Patterns

scholarly journals Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

2021 ◽  
Author(s):  
sheng Qiu ◽  
Zerong Liang ◽  
Qinan Wu ◽  
Miao Wang ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

scholarly journals Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism

2017 ◽  
Vol 18 (7) ◽  
pp. 1330 ◽  
Author(s):  
Manal Almatrafi ◽  
Marcela Vergara-Jimenez ◽  
Ana Murillo ◽  
Gregory Norris ◽  
Christopher Blesso ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Guinea Pigs ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Expression Of Genes

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 Hepatic Lipid Accumulation and Nrf2 Expression following Perinatal and Peripubertal Exposure to Bisphenol A in a Mouse Model of Nonalcoholic Liver Disease

2017 ◽  
Vol 125 (8) ◽  
pp. 087005 ◽  
Author(s):  
Prajakta C. Shimpi ◽  
Vijay R. More ◽  
Maneesha Paranjpe ◽  
Ajay C. Donepudi ◽  
Jaclyn M. Goodrich ◽  
...  
Keyword(s):  
Liver Disease ◽  
Mouse Model ◽  
Bisphenol A ◽  
Lipid Accumulation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Nrf2 Expression ◽  
Nonalcoholic Liver Disease

Dysregulated Autophagy in Hepatocytes Promotes Bisphenol A–Induced Hepatic Lipid Accumulation in Male Mice

Endocrinology ◽  
2017 ◽  
Vol 158 (9) ◽  
pp. 2799-2812 ◽  
Author(s):  
Shumin Yang ◽  
Aipin Zhang ◽  
Ting Li ◽  
Rufei Gao ◽  
Chuan Peng ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Lipid Accumulation ◽  
Male Mice ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation
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