Protective Effect of Gallic Acid against Nonalcoholic Fatty Liver Disease Induced by High Fat Diet

Liver is considered as significant organ within body. Aims: Our survey aimed in illustrating protective effectiveness of gallic acid (GA) against high fat regimen nonalcoholic fatty liver disease (NAFLD). Study design: In our study, Rats were classified into 3 groups; control, orally given fatty-sucrosed diet, gallic acid treated groups. Methodology: They were evaluated through measuring hepatic cholesterol and triglyceride, alanine and aspartate aminotransferases and gammaglutamyl-transferase; total, direct and indirect bilirubin; total protein, albumin and globulin; hepatic and adipose malondialdehyde, glutathione-S-transferase, superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase activities; glucose, insulin, homeostasis model assessment of insulin resistance, leptin and adiponectin; tumor necrosis factor alpha, interleukin-17 and interleukin-1beta; fatty acid synthase, acetyl-Coenzyme A carboxylase-α and HMGCoA reductase. Results: Our results demonstrated that GA ameliorated the elevated lipid, serum liver function enzymes, bilirubin and the decreased L.glycogen levels and serum protein profile. GA improved the hepatic and adipose antioxidants activities by decreasing MDA and increasing GST, SOD, Cat, GSH and GPx activities. GA ameliorated the elevated Glu, INS, HOMA-IR, LEP and the decreased adiponectin levels. Moreover, GA ameliorated the elevated TNF-α, IL-17, IL-1β, FAS, ACC-α and HMGCR levels. Liver and adipose histopathologies confirmed our results. Conclusion: Gallic acid intake exhibited a beneficial therapeutic effect on nonalcoholic fatty liver disease rats as anti-inflammatory and antioxidant agent.

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Maternal Hypoxia Increases the Susceptibility of Adult Rat Male Offspring to High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease

Endocrinology ◽

10.1210/en.2012-1683 ◽

2013 ◽

Vol 154 (11) ◽

pp. 4377-4387 ◽

Cited By ~ 9

Author(s):

Yi-Ming Su ◽

Guo-Rong Lv ◽

Jing-Xian Xie ◽

Zhen-Hua Wang ◽

Hui-Tong Lin

Keyword(s):

Liver Disease ◽

Protein Kinase ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Fatty Acid Synthase ◽

Protein Kinase B ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Maternal Hypoxia

Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD.

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Combined treatments with metformin and phosphodiesterase inhibitors alleviate nonalcoholic fatty liver disease in high-fat diet fed rats: a comparative study

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0487 ◽

2020 ◽

Vol 98 (8) ◽

pp. 498-505

Author(s):

Gehan H. Heeba ◽

Reham M. El-Deen ◽

Rania G. Abdel-latif ◽

Mohamed M.A. Khalifa

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Phosphodiesterase Inhibitors ◽

Model Assessment ◽

High Fat ◽

Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is an excessive accumulation of fats in the liver resulting in hepatic inflammation and fibrous tissue formation along with insulin resistance. This study was designed to investigate the possible protective effects of metformin alone and in combination with different phosphodiesterase inhibitors (PDEIs). Rats were fed a high-fat diet (HFD) for 16 weeks to induce NAFLD. Starting from week 12, rats received metformin alone or in combination with pentoxifylline, cilostazol, or sildenafil. HFD administration resulted in hepatic steatosis and inflammation in rats. In addition, liver index, body composition index, activities of liver enzymes, and serum lipids deviated from normal. Further, significant elevations were recorded compared to control in terms of serum glucose, insulin, and HOMA-IR (homeostasis model assessment index for insulin resistance), oxidative stress parameters, hepatic TNF-α and NF-κB gene expression, and iNOS protein expression. Rats treated with metformin showed a significant improvement in the aforementioned parameters. However, the addition of pentoxifylline to metformin treatment synergized its action and produced a fortified effect against HFD-induced NAFLD better than other PDEIs. Data from this study indicated that combined treatment of metformin and pentoxifylline had the most remarkable ameliorated effects against HFD-induced NAFLD; further clinical investigations are needed to approve PDEIs for NAFLD treatment.

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Emodin palliates high-fat diet-induced nonalcoholic fatty liver disease in mice via activating the farnesoid X receptor pathway

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114340 ◽

2021 ◽

pp. 114340

Author(s):

Chuangpeng Shen ◽

Zhisen Pan ◽

Shuangcheng Wu ◽

Mingxuan Zheng ◽

Chong Zhong ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Farnesoid X Receptor ◽

High Fat ◽

Nonalcoholic Fatty Liver

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SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21124534 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4534

Author(s):

Da Eun Kim ◽

Bo Yoon Chang ◽

Byeong Min Jeon ◽

Jong In Baek ◽

Sun Chang Kim ◽

...

Keyword(s):

Lipid Metabolism ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Signaling Pathway ◽

Hepg2 Cells ◽

Fatty Liver Disease ◽

Fatty Acid Synthase ◽

Density Lipoprotein ◽

Nonalcoholic Fatty Liver

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

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Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic fatty liver disease induced by a high-fat and high-carbohydrate diet in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00291.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. G496-G504 ◽

Cited By ~ 18

Author(s):

Akihiro Asai ◽

Pauline M. Chou ◽

Heng-Fu Bu ◽

Xiao Wang ◽

M. Sambasiva Rao ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Hepatic Steatosis ◽

Fatty Liver Disease ◽

Diet Group ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Akt Phosphorylation ◽

High Carbohydrate

Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and diet. It is associated with insulin resistance (IR) in hepatic and peripheral tissues. Here, we aimed to characterize the severity of diet-induced steatosis, obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high-carbohydrate (HFHC) or control diet for 16 wk followed by the application of a combination of classic physiological, biochemical, and pathological studies to determine obesity and hepatic steatosis. Peripheral IR was characterized by measuring blood glucose level, serum insulin level, homeostasis model assessment of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in adipose tissues, whereas the level of hepatic IR was determined by measuring insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J and DBA/2J mice developed obesity to a similar degree without the feature of liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice in the HFHC diet group developed only a mild degree of pericentrilobular hepatic steatosis that was associated with moderate changes in peripheral IR. Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC diet treatment. Collectively, these data suggest that the severity of diet-induced hepatic steatosis is correlated to the level of peripheral IR, not with the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a dominant factor of pathophysiology in nonalcoholic fatty liver disease.

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