Zoledronic acid prevents the hepatic changes associated with high fat diet in rats; the potential role of mevalonic acid pathway in nonalcoholic steatohepatitis

2019 ◽  
Vol 858 ◽  
pp. 172469 ◽  
Author(s):  
Reham Hussein Mohamed ◽  
Maha Tarek ◽  
Ghada Galal Hamam ◽  
Samar F. Ezzat
Keyword(s):  
Zoledronic Acid ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Potential Role ◽  
Mevalonic Acid ◽  
High Fat ◽  
Mevalonic Acid Pathway ◽  
Acid Pathway

scholarly journals Deficiency of the Purinergic Receptor 2X7 Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Claudia Blasetti Fantauzzi ◽  
Stefano Menini ◽  
Carla Iacobini ◽  
Chiara Rossi ◽  
Eleonora Santini ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Purinergic Receptor ◽  
High Fat ◽  
Liver Sinusoidal Endothelial Cells ◽  
Nonalcoholic Fatty Liver ◽  
Markers Of Inflammation

Molecular mechanisms driving transition from simple steatosis to nonalcoholic steatohepatitis (NASH), a critical step in the progression of nonalcoholic fatty liver disease (NAFLD) to cirrhosis, are poorly defined. This study aimed at investigating the role of the purinergic receptor 2X7 (PR2X7), through the NLRP3 inflammasome, in the development of NASH. To this end, mice knockout for the Pr2x7 gene (Pr2x7−/−) and coeval wild-type (WT) mice were fed a high-fat diet (HFD) or normal-fat diet for 16 weeks. NAFLD grade and stage were lower in Pr2x7−/− than WT mice, and only 1/7 Pr2x7−/− animals showed evidence of NASH, as compared with 4/7 WT mice. Molecular markers of inflammation, oxidative stress, and fibrosis were markedly increased in WT-HFD mice, whereas no or significantly reduced increments were detected in Pr2x7−/− animals, which showed also decreased modulation of genes of lipid metabolism. Deletion of Pr2x7 gene was associated with blunted or abolished activation of NLRP3 inflammasome and expression of its components, which were induced in liver sinusoidal endothelial cells challenged with appropriate stimuli. These data show that Pr2x7 gene deletion protects mice from HFD-induced NASH, possibly through blunted activation of NLRP3 inflammasome, suggesting that PR2X7 and NLRP3 may represent novel therapeutic targets.

scholarly journals Potential Role of Central Microglia Activation in High Fat Diet‐Induced Obesity

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Aneesh Singal ◽  
Caitlin R. Coker ◽  
Sarah S. Bingaman ◽  
Amy C. Arnold ◽  
Yuval Silberman
Keyword(s):  
High Fat Diet ◽  
Potential Role ◽  
Microglia Activation ◽  
High Fat ◽  
Diet Induced Obesity

scholarly journals Glucagon-like peptide-2 and mouse intestinal adaptation to a high-fat diet

2013 ◽  
Vol 217 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Sara Baldassano ◽  
Antonella Amato ◽  
Francesco Cappello ◽  
Francesca Rappa ◽  
Flavia Mulè
Keyword(s):  
High Fat Diet ◽  
Caspase 3 ◽  
Potential Role ◽  
Intestinal Adaptation ◽  
Cell Number ◽  
Standard Diet ◽  
High Fat ◽  
Villus Height ◽  
Glucagon Like Peptide

Endogenous glucagon-like peptide-2 (GLP2) is a key mediator of refeeding-induced and resection-induced intestinal adaptive growth. This study investigated the potential role of GLP2 in mediating the mucosal responses to a chronic high-fat diet (HFD). In this view, the murine small intestine adaptive response to a HFD was analyzed and a possible involvement of endogenous GLP2 was verified using GLP2 (3–33) as GLP2 receptor (GLP2R) antagonist. In comparison with animals fed a standard diet, mice fed a HFD for 14 weeks exhibited an increase in crypt–villus mean height (duodenum, 27.5±3.0%; jejunum, 36.5±2.9%;P<0.01), in the cell number per villus (duodenum, 28.4±2.2%; jejunum, 32.0±2.9%;P<0.01), and in Ki67-positive cell number per crypt. No change in the percent of caspase-3-positive cell in the villus–crypt was observed. The chronic exposure to a HFD also caused a significant increase in GLP2 plasma levels and in GLP2R intestinal expression. Daily administration of GLP2 (3–33) (30–60 ng) for 4 weeks did not modify the crypt–villus height in control mice. In HFD-fed mice, chronic treatment with GLP2 (3–33) reduced the increase in crypt–villus height and in the cell number per villus through reduction of cell proliferation and increase in apoptosis. This study provides the first experimental evidence for a role of endogenous GLP2 in the intestinal adaptation to HFD in obese mice and for a dysregulation of the GLP2/GLP2R system after a prolonged HFD.

miR-182-5p Attenuates High-Fat -Diet-Induced Nonalcoholic Steatohepatitis in Mice

2018 ◽  
Vol 17 (5) ◽  
pp. 0-10
Author(s):  
Qionghe Liang ◽  
Huan Chen ◽  
Xiaoqun Xu ◽  
Weiwei Jiang
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Treated Group ◽  
High Fat ◽  
Protein Levels ◽  
Tlr4 Mrna ◽  
Increased Risk

Introduction and Aim: Patients with NASH have increased risk for sepsis or cardiovascular disease after Liver transplantation. An important role of Toll-like receptor (TLR) 4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) was demonstrated. Here, we study the role of miR-182-5p in TLR4 expression and high-fat-diet (HFD)-induced NASH in vitro and in vivo. Methods: Following transfection with a miR-182-5p mimic, the effect of miR-182-5p on TLR4 in RAW264.7 and HepG2 cells was investigated. Following administration of the miR-182-5p mimic into the livers of HFD-induced NASH mice, we determined the in vivo expression of TLR4, TNFα, and IL-6 and assessed the histologic features of the livers. Results: Following lipopolysaccharide (LPS) treatment of RAW264.7 cells, real-time RT-PCR and western blot results indicated decreases levels of TLR4 mRNA and protein in the miR-182-5p group as compared with levels observed in controls, with similar trends were observed in TNFα and IL-6 protein levels. Following oleic acid (OA) treatment of HepG2 cells, TLR4, TNFα, and IL-6 levels were significantly decreased in the miR-182-5p group as compared with levels observed in controls. Following miR-182-5p administration, TLR4 mRNA and protein levels decreased along with those of TNFα and IL-6 proteins, and the liver weight/body weight ratio of treated mice was less than that observed in controls. Furthermore, hematoxylin and eosin staining showed that the miR-182-5p-treated group exhibited low adipose-cell cross-sectional areas, and Oil Red O staining showed decreases in the size of lipid droplets in the miR-182-5p-treated group. Conclusions: miR-182-5p ameliorated HFD-induced NASH by suppressing TLR4.

[696] ROLE OF MELATONIN IN TREATMENT OF NONALCOHOLIC STEATOHEPATITIS IN RATS INDUCED BY HIGH FAT DIET

2007 ◽  
Vol 46 ◽  
pp. S263 ◽  
Author(s):  
N. Kuzu ◽  
I.H. Bahcecioglu ◽  
K. Metin ◽  
I.H. Ozercan ◽  
M. Tuzcu ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
High Fat

ADAMTS13 deficiency promotes microthrombosis in a murine model of diet-induced liver steatosis

2017 ◽  
Vol 117 (01) ◽  
pp. 19-26 ◽  
Author(s):  
Lotte Geys ◽  
Dries Bauters ◽  
Elien Roose ◽  
Claudia Tersteeg ◽  
Karen Vanhoorelbeke ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Potential Role ◽  
Liver Steatosis ◽  
High Fat ◽  
Markers Of Inflammation ◽  
Normal Chow ◽  
Adamts13 Deficiency ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryADAMTS13 cleaves ultralarge multimeric von Willebrand Factor (VWF), thereby preventing formation of platelet-rich microthrombi. ADAMTS13 is mainly produced by hepatic stellate cells, and numerous studies have suggested a functional role of ADAMTS13 in the pathogenesis of liver diseases. The aim of our study was to investigate a potential role of ADAMTS13 in formation of hepatic microthrombi and development of non-alcoholic steatohepatitis (NASH), and furthermore to evaluate whether plasmin can compensate for the absence of ADAMTS13 in removal of thrombi. Therefore, we used a model of high-fat diet-induced steatosis in Adamts13 deficient (Adamts13−/−) and wild-type (WT) control mice. Microthrombi were more abundant in the liver of obese Adamts13−/− as compared to obese WT or to lean Adamts13−/− mice. Obese Adamts13−/− mice displayed lower platelet counts and higher prevalence of ultra-large VWF multimers. Hepatic plasmin-α2-antiplasmin complex levels were comparable for obese WT and Adamts13−/− mice and were lower for lean Adamts13−/− than WT mice, not supporting marked activation of the fibrinolytic system. High fat diet feeding, as compared to normal chow, resulted in enhanced liver triglyceride levels for both genotypes (p < 0.0001) and steatosis (p < 0.0001 for WT mice, p = 0.002 for Adamts13−/− mice) without differences between the genotypes. Expression of markers of inflammation, oxidative stress, steatosis and fibrosis was affected by diet, but not by genotype. Thus, our data confirm that obesity promotes NASH, but do not support a detrimental role of ADAMTS13 in its development. However, Adamts13 deficiency in obese mice promotes hepatic microthrombosis, whereas a compensatory role of plasmin in removal of microthrombi in the absence of ADAMTS13 could not be demonstrated.

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