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 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.

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

scholarly journals Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

2018 ◽  
Vol 49 (5) ◽  
pp. 1870-1884 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ciao-Han Wei ◽  
Ya-Ling Chen ◽  
Ching-Yi Cheng ◽  
Chia-Ling Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Epididymal Adipose Tissue ◽  
Obese Mice ◽  
High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

scholarly journals The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice

2020 ◽  
Vol 61 (7) ◽  
pp. 1052-1064 ◽  
Author(s):  
Minjuan Ma ◽  
Rui Duan ◽  
Lulu Shen ◽  
Mengting Liu ◽  
Yaya Ji ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Lipid Deposition ◽  
In Vivo Models ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Regulatory Circuit ◽  
Murine Liver

Excessive lipid deposition is a hallmark of NAFLD. Although much has been learned about the enzymes and metabolites involved in NAFLD, few studies have focused on the role of long noncoding RNAs (lncRNAs) in hepatic lipid accumulation. Here, using in vitro and in vivo models of NAFLD, we found that the lncRNA Gm15622 is highly expressed in the liver of obese mice fed a HFD and in murine liver (AML-12) cells treated with free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on lipid accumulation in hepatocytes and on NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator SREBP-1c and promoted lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice. In conclusion, we have identified an lncRNA Gm15622/miR-742-3p/SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD.

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.

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