scholarly journals Hepatoprotective Effects of MHY3200 on High-Fat, Diet-Induced, Non-Alcoholic Fatty Liver Disease in Rats

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2057 ◽  
Author(s):  
Min Jo Kim ◽  
Chan Hum Park ◽  
Dae Hyun Kim ◽  
Min Hi Park ◽  
Kyung Chul Park ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Serum Triglyceride ◽  
Serine Phosphorylation ◽  
Luciferase Assay ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

This study investigated the effects of 2-(4-(5-chlorobenzo[d]thiazol-2-yl)phenoxy)-2,2-difluoroacetic acid (MHY3200) on high-fat diet (HFD)-induced hepatic lipid accumulation and inflammation. The measurement of peroxisome proliferator-activated receptor (PPAR)α activity by using a luciferase assay indicated that MHY3200 was more potent than a known PPARα agonist, WY14643, in AC2F cells. Six-month-old male SD rats were fed chow or HFD for 1 month, and after, with or without added MHY3200 (1 or 2 mg/kg/day) for 4 weeks. The oral administration of MHY3200 caused a significant decrease in serum triglyceride (TG), glucose, alanine aminotransferase, and insulin, as well as a slight decrease in the level of free fatty acid and aspartate transaminase. No weight gain was detected when compared with HFD rats, and hepatic TG content was also attenuated by the administration of MHY3200. Furthermore, phosphorylation of the ER stress marker, inositol-requiring kinase 1 and its downstream gene, c-Jun N-terminal kinase, in addition to serine phosphorylation of insulin receptor substrate 1 were suppressed by MHY3200. Consistent with these results, MHY3200 administration reduced the levels of activation of protein-1, cyclooxygenase-2, and inducible nitric oxide synthase. Our results suggested that MHY3200 ameliorated HFD-induced hepatic lipid accumulation and inflammation, and improved insulin resistance through PPARα activation.

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.

Uridine attenuates obesity, ameliorates hepatic lipid accumulation and modifies the gut microbiota composition in mice fed with a high-fat diet

2021 ◽  
Author(s):  
Yilin Liu ◽  
Chunyan Xie ◽  
Zhenya Zhai ◽  
Ze-yuan Deng ◽  
Hugo R. De Jonge ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Microbiota Composition ◽  
High Fat ◽  
Fat Accumulation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Gut Microbiota Composition

This study aimed to investigate the effect of uridine on obesity, fat accumulation in liver, and gut microbiota composition in high-fat diet-fed mice.

Vitamin D Deficiency Attenuates High-Fat Diet-Induced Hyperinsulinemia and Hepatic Lipid Accumulation in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (6) ◽  
pp. 2103-2113 ◽  
Author(s):  
Xiao-Jing Liu ◽  
Bi-Wei Wang ◽  
Cheng Zhang ◽  
Mi-Zhen Xia ◽  
Yuan-Hua Chen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Male Mice ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Lychee pulp phenolics ameliorate hepatic lipid accumulation by reducing miR-33 and miR-122 expression in mice fed a high-fat diet

2017 ◽  
Vol 8 (2) ◽  
pp. 808-815 ◽  
Author(s):  
Dongxiao Su ◽  
Ruifen Zhang ◽  
Fangli Hou ◽  
Jianwei Chi ◽  
Fei Huang ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

The repression of miR-33 and miR-122 is a possible molecular mechanism of the hypolipidemic effects of lychee pulp phenolics.

Supplementation of a High-Fat Diet with Chlorogenic Acid Is Associated with Insulin Resistance and Hepatic Lipid Accumulation in Mice

2013 ◽  
Vol 61 (18) ◽  
pp. 4371-4378 ◽  
Author(s):  
Aidilla Mubarak ◽  
Jonathan M. Hodgson ◽  
Michael J. Considine ◽  
Kevin D. Croft ◽  
Vance B. Matthews
Keyword(s):  
Insulin Resistance ◽  
Chlorogenic Acid ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

scholarly journals Optimized Rapeseed Oils Rich in Endogenous Micronutrients Protect High Fat Diet Fed Rats from Hepatic Lipid Accumulation and Oxidative Stress

Nutrients ◽  
2015 ◽  
Vol 7 (10) ◽  
pp. 8491-8502 ◽  
Author(s):  
Jiqu Xu ◽  
Xiaoli Liu ◽  
Hui Gao ◽  
Chang Chen ◽  
Qianchun Deng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
And Oxidative Stress
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