Apple Pomace as a Novel Aid for Western Diet-Induced Nonalcoholic Fatty Liver Disease in Young Female Sprague Dawley Rats

Objective To examine the effects of arnebin-1 on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). Methods Male Sprague–Dawley rats were fed an HFD for 10 weeks and then treated with arnebin-1 at a dose of 5, 10 or 20 mg/kg/day by gavage for a further 12 weeks of a 22-week HFD. Peripheral blood and liver tissues were collected for biochemical and histopathological examination. The mechanisms of arnebin-1 on liver fibrosis and insulin resistance (IR) were determined by Western blotting and real-time quantitative polymerase chain reaction. Results Arnebin-1 treatment attenuated the increase of total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase in serum and lipid accumulation in the livers of HFD-fed rats. Furthermore, arnebin-1 abrogated HFD-induced liver fibrosis and the increase of fibrotic biomarkers. The HFD-induced decrease of hepatic proliferator-activated receptor γ and pro-matrix-metalloproteinase (MMP)-9 levels and the increase of tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were reversed after arnebin-1. Arnebin-1 attenuated IR through activating the insulin receptor substrate-1/Akt/mTOR signalling pathway. Conclusion This study demonstrated that arnebin-1 ameliorates NAFLD, in part, by attenuating hepatic fibrosis and IR, suggesting that arnebin-1 may be a therapeutic agent for NAFLD treatment.

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Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease

Antioxidants ◽

10.3390/antiox10040559 ◽

2021 ◽

Vol 10 (4) ◽

pp. 559

Author(s):

Yi-Long Huang ◽

Zhao-Qing Shen ◽

Chen-Hua Huang ◽

Yuan-Chi Teng ◽

Chao-Hsiung Lin ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Liver Diseases ◽

Cholesterol Biosynthesis ◽

Severe Form ◽

Western Diet ◽

Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are the most common chronic liver diseases worldwide. However, drugs to treat NAFLD and NASH are an unmet clinical need. This study sought to provide evidence that Cisd2 is a molecular target for the development of treatments targeting NAFLD and NASH. Several discoveries are pinpointed. The first is that Cisd2 dosage modulates the severity of Western diet-induced (WD-induced) NAFLD. Specifically, Cisd2 haploinsufficiency accelerates NAFLD development and exacerbates progression toward NASH. Conversely, an enhanced Cisd2 copy number attenuates liver pathogenesis. Secondly, when a WD is fed to mice, transcriptomic analysis reveals that the major alterations affecting biological processes are related to inflammation, lipid metabolism, and DNA replication/repair. Thirdly, among these differentially expressed genes, the most significant changes involve Nrf2-mediated oxidative stress, cholesterol biosynthesis, and fatty acid metabolism. Finally, increased Cisd2 expression protects the liver from oxidative stress and reduces the occurrence of mitochondrial DNA deletions. Taken together, our mouse model reveals that Cisd2 plays a crucial role in protecting the liver from WD-induced damages. The development of therapeutic agents that effectively enhance Cisd2 expression is one potential approach to the treatment of WD-induced fatty liver diseases.

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Correction to Hepatic Lipidomics Analysis Reveals the Ameliorative Effects of Highland Barley β-Glucan on Western Diet-Induced Nonalcoholic Fatty Liver Disease Mice

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.1c07655 ◽

2021 ◽

Author(s):

Huicui Liu ◽

Tao Chen ◽

Xiaoqing Xie ◽

Xinlei Wang ◽

Yiwen Luo ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Western Diet ◽

Nonalcoholic Fatty Liver ◽

Highland Barley

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Jiangzhi Ligan Decoction Inhibits GSDMD-Mediated Canonical/Noncanonical Pyroptosis Pathways and Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease

Disease Markers ◽

10.1155/2021/9963534 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Kangkang Yin ◽

Xiao Zhou ◽

Wei Jiang ◽

Linlin Wang ◽

Ziwei Dai ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Serum Levels ◽

Vital Role ◽

Sprague Dawley ◽

High Fat ◽

Nonalcoholic Fatty Liver

Increasing evidence suggests that gasdermin D (GSDMD) mediated pyroptosis signaling pathways play a vital role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Jiangzhi Ligan Decoction (JZLGD) has been verified to prevent NAFLD, but its specific mechanism has not been determined. In this study, an NAFLD model was established in Sprague-Dawley rats by a high-fat diet (HFD). After 12 weeks, JZLGD was orally administered once a day for 6 additional weeks. We investigated the effects of JZLGD on NAFLD rats and determined the GSDMD pathway-associated proteins to explore whether such effects were associated with pyroptosis. Our data show that JZLGD significantly reduced the liver index; improved serum lipid levels, liver function parameters, and lipid droplet content; and relieved NAFLD. We further found that the serum levels of the proinflammatory factors interleukin-1β (IL-1β), IL-18, tumor necrosis factor-α, and IL-6 were obviously decreased in the JZLGD group. HFD rats treated with GSDMD exhibited NLRP3, caspase-1, lipopolysaccharide (LPS), and caspase-11 activation; however, these effects were blunted by JZLGD treatment. Taken together, JZLGD may exert hepatoprotective effects against NAFLD in a rat HFD model by regulating GSDMD-mediated canonical/noncanonical pyroptosis pathways.

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