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

Basma S. Ismail ◽  
Eman S. Abdel-Reheim ◽  
Hanan A. Soliman ◽  
Basant Mahmoud

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Kangkang Yin ◽  
Xiao Zhou ◽  
Wei Jiang ◽  
Linlin Wang ◽  
Ziwei Dai ◽  

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.

2014 ◽  
Vol 306 (6) ◽  
pp. G496-G504 ◽  
Akihiro Asai ◽  
Pauline M. Chou ◽  
Heng-Fu Bu ◽  
Xiao Wang ◽  
M. Sambasiva Rao ◽  

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.

2016 ◽  
Vol 311 (4) ◽  
pp. G587-G598 ◽  
Abdul Soofi ◽  
Katherine I. Wolf ◽  
Egon J. Ranghini ◽  
Mohammad A. Amin ◽  
Gregory R. Dressler

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and is increasing with the rising rate of obesity in the developed world. Signaling pathways known to influence the rate of lipid deposition in liver, known as hepatic steatosis, include the transforming growth factor (TGF) superfamily, which function through the SMAD second messengers. The kielin/chordin-like protein (KCP) is a large secreted protein that can enhance bone morphogenetic protein signaling while suppressing TGF-β signaling in cells and in genetically modified mice. In this report, we show that aging KCP mutant ( Kcp −/−) mice are increasingly susceptible to developing hepatic steatosis and liver fibrosis. When young mice are put on a high-fat diet, Kcp −/− mice are also more susceptible to developing liver pathology, compared with their wild-type littermates. Furthermore, mice that express a Pepck-KCP transgene ( Kcp Tg) in the liver are resistant to developing liver pathology even when fed a high-fat diet. Analyses of liver tissues reveal a significant reduction of P-Smad3, consistent with a role for KCP in suppressing TGF-β signaling. Transcriptome analyses show that livers from Kcp −/− mice fed a normal diet are more like wild-type livers from mice fed a high-fat diet. However, the KCP transgene can suppress many of the changes in liver gene expression that are due to a high-fat diet. These data demonstrate that shifting the TGF-β signaling paradigm with the secreted regulatory protein KCP can significantly alter the liver pathology in aging mice and in diet-induced NAFLD.

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