Enhanced Inflammatory Reaction and Thrombosis in High-Fat Diet-Fed ApoE-/- Mice are Attenuated by Celastrol

2020 ◽  
Author(s):  
Mao Ouyang ◽  
Tao Qin ◽  
Hengdao Liu ◽  
Junya Lu ◽  
Caixia Peng ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Matrix Metalloproteinase ◽  
Inflammatory Reaction ◽  
High Fat Diet ◽  
Mononuclear Cells ◽  
Matrix Metalloproteinase 2 ◽  
Mice Model ◽  
High Fat ◽  
Peripheral Blood Mononuclear ◽  
Apo E

Abstract Objective High-fat diet (HFD) increases the risk of inflammatory reaction and acute arterial thrombosis. Celastrol has been confirmed to regulate inflammatory cytokine levels in atherosclerotic animal models. However, the anti-thrombotic effects of celastrol have remained to be fully demonstrated. The present study was performed to investigate the beneficial effect of celastrol in HFD-induced inflammatory reaction and thrombosis in apolipoprotein (apo)E-/- mice. Materials and Methods Thrombogenic mice model was established using HFD-fed apoE-/- mice. The levels of mRNA and protein were assayed by RT-qPCR and western blotting, respectively. Immunohistochemistry (IHC) staining was performed to measure the protein expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the aortic endothelium of HFD-fed apoE-/- mice. Results The results demonstrated that the effect of HFD on inflammatory cytokines in mice with apoE-/- background was reversed by celastrol administration, and celastrol treatment inhibited the NOD-like receptor family, pyrin domain containing 3 (NLRP3)/caspase-1/interleukin-1β signaling cascades in peripheral blood mononuclear cells from HFD-fed apoE-/- mice. In addition, HFD enhanced adenosine diphosphate-induced platelet aggregation in normal C57BL/6 and apoE-/- mice, while celastrol administration reversed this. Furthermore, celastrol inhibited the pro-thrombotic effects of HFD in apoE-/- mice, and the underlying mechanism was mediated, at least partially, through the suppression of matrix metalloproteinase-2 and -9 expression. Conclusions Celastrol administration significantly attenuated HFD-induced inflammatory reaction, platelet aggregation and thrombosis in apoE-/- mice, and celastrol may be used as a drug for the prevention of HFD-induced inflammatory reaction and thrombus.

scholarly journals Effect of high-fat diet on peripheral blood mononuclear cells and adipose tissue in early stages of diet-induced weight gain

2019 ◽  
Vol 122 (12) ◽  
pp. 1359-1367 ◽  
Author(s):  
Jake E. Lowry ◽  
Batbayar Tumurbaatar ◽  
Claudia D’Agostino ◽  
Erika Main ◽  
Traver J. Wright ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
High Fat Diet ◽  
Time Course ◽  
Mononuclear Cells ◽  
High Fat ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Inflammatory Changes

AbstractSubcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.

scholarly journals High Fat Diet Induces Adhesion of Platelets to Endothelium in Two Models of Dyslipidemia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jaime Gonzalez ◽  
Wendy Donoso ◽  
Natalia Díaz ◽  
María Eliana Albornoz ◽  
Ricardo Huilcaman ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Early Stage ◽  
Endothelial Activation ◽  
Mice Model ◽  
High Fat ◽  
Early Stages ◽  
Endothelial Surface ◽  
Two Stages ◽  
Adhesion Of Platelets

Cardiovascular diseases (CVD) represent about 30% of all global deaths. It is currently accepted that, in the atherogenic process, platelets play an important role, contributing to endothelial activation and modulation of the inflammatory phenomenon, promoting the beginning and formation of lesions and their subsequent thrombotic complications. The objective of the present work was to study using immunohistochemistry, the presence of platelets, monocytes/macrophages, and cell adhesion molecules (CD61, CD163, and CD54), in two stages of the atheromatous process. CF-1 mice fed a fat diet were used to obtain early stages of atheromatous process, denominated early stage of atherosclerosis, and ApoE−/−mice fed a fat diet were used to observe advanced stages of atherosclerosis. The CF-1 mice model presented immunostaining on endothelial surface for all three markers studied; the advanced atherosclerosis model in ApoE−/−mice also presented granular immunostaining on lesion thickness, for the same markers. These results suggest that platelets participate in atheromatous process from early stages to advance d stages. High fat diet induces adhesion of platelets to endothelial cellsin vivo. These findings support studying the participation of platelets in the formation of atheromatous plate.

scholarly journals The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial

2018 ◽  
Vol 315 (6) ◽  
pp. R1210-R1219 ◽  
Author(s):  
Étienne Myette-Côté ◽  
Cody Durrer ◽  
Helena Neudorf ◽  
Tyler D. Bammert ◽  
José Diego Botezelli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
High Fat ◽  
Peripheral Blood Mononuclear ◽  
Time Interaction ◽  
Low Carbohydrate

Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (−5%, P < 0.05), whereas both LC+Ex (−16%, P < 0.001) and LC (−12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: −32%, LC: −45%, and LC+Ex: −44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (−76%, P = 0.035) and a tendency for a reduction in LC (−70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (−27%, P = 0.001) and LC+Ex (−35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.

Hepatotoxic Effect of Lafoensia pacari A. St. Hil. (Lythraceae) on a DietInduced Obese Mice Model

2021 ◽  
Vol 28 ◽  
Author(s):  
Natália Gonçalves Ribeiro ◽  
Fabio Ribeiro dos Santos ◽  
Janaína Ribeiro Oliveira ◽  
Amanda Souto Machado ◽  
Deborah de Faria Lelis ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Histological Analysis ◽  
Liver Weight ◽  
Phytochemical Analysis ◽  
Mice Model ◽  
High Fat ◽  
Plant Parts ◽  
Oral Consumption ◽  
Hepatotoxic Effect ◽  
Brazilian Flora

Background: Brazilian flora is rich in plants with medicinal properties, which though popular, has contributed to the development of a range of homeopathic products that use plants to treat and cure diseases. However, studies that use Brazilian plants in the treatment of metabolic disorders are still scarce in the literature. Objective: The aim of this study was to analyze the effect of hepatotoxicity Lafoensia pacari on the metabolism of mice with obesity induced by a high-fat diet and to verify the phytochemical difference between the Lafoensia pacari bark of the trunk, leaves, and branches. Methods: The plant material was collected from April to May in the municipality of Bonito de Minas, MG, Brazil. Qualitative tests for the presence of classes of secondary metabolites were performed for leaves, branches and bark of the trunk. Through histological analysis, we evaluated hepatocytes and cell lesions in the liver. Results: The comparative phytochemical analysis of the plant did not reveal alterations between the different plant parts. The phytochemical teste showed that is preferable to use the leaves to make the extract to be applied, aiming to reduce the plant aggression. After treatment, greater changes were observed in the animals that received the high-fat diet and the hydroethanolic extract; the levels of AST, ALT, albumin and creatinine that were increased, thus demonstrating a possible toxicity. There were no significant differences in body weight. In the histological analysis, the animals that received any treatments with the plant, displayed decreased liver weight and reduction in the inflammatory infiltrate. Conclusion: We conclude that Lafoensia pacari should be better evaluated for oral consumption and may cause liver damage.

Osteocalcin prevents insulin resistance, hepatic inflammation and autophagy associated with high-fat diet induced fatty liver hemorrhagic syndrome in aged laying hens

2020 ◽  
Author(s):  
Xiaoling Wu ◽  
Xinyu Zou ◽  
Mi Zhang ◽  
Haiqiang Hu ◽  
Xueliang Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Inflammatory Reaction ◽  
High Fat Diet ◽  
Laying Hens ◽  
Density Lipoprotein ◽  
Inflammatory Factors ◽  
Pathological Changes ◽  
High Fat ◽  
Tnf Α

Abstract Background: Osteocalcin (OCN), as an energy-regulating hormone, involves in preventing nonalcoholic steatohepatitis. Laying hens have been used as an animal model for investigating liver function and related metabolic disordersas that the synthesis of fat in laying hens is much faster than in mammals with limited adipose tissue. The aim of this study was to investigate the effects of OCN on fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Methods: Thirty 68-week-old White Plymouth laying hens were randomly assigned into conventional single-bird cages, and the cages were randomly allocated into one of three treatments: normal diet (ND + vehicle , ND+V), high-fat diet (HFD + vehicle, HFD+V), and HFD + OCN (3 μg/bird, 1 time/2 days, i.m.) for 40 days. At experimental day 30, oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were performed. At the end of experiment, the hens were euthanized followed blood collection. The plasma aspartate transaminase (AST), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automatic biochemistry analyzer. Pathological changes in the liver were examined under both light and transmission electron microscopes. The plasma inflammatory factors including interleukin-1 (IL-1), IL-6, and tumor Necrosis Factor-alpha (TNF-α) were analyzed by ELISA, and the gene expressions of these inflammatory factors in the liver were analyzed by Real-time PCR. And oxidative stress was evaluated using Malondialdehyde (MDA) and Glutathione peroxidase (GSH-Px) assay kits. Results: The results showed HFD hens had more severe liver haemorrhage and fibrosis than ND hens. The ultra-microstructural examination showed that hepatocytes of HFD hens appeared necrotic pyknosis associated with great intracellular electron, mitochondrial swelling, shrunk nucleus and absence of autolysosomes. OCN mitigated these pathological changes by improved HFD hens’ insulin resistance via alleviating the glucose intolerence and improving insulin sensitivity; inhibited HFD-induced oxidative stress as evidenced by decreased liver concentrations of MDA but increased GSH-Px; and reduced the inflammatory reaction with reducing blood IL-6 and TNF-α concentrations and mRNA expressions. Conclusion: These results suggest a high-fat diet promotes the FLHS development in aged hens, while OCN prevents the FLHS process through inhibiting insulin resistance, inflammatory reaction, oxidative stress and fibrosis, and acting autophagy.

scholarly journals Age-related change in anti-platelet aggregation in feeding of a high fat diet and ω-3 fatty acid in rats

1995 ◽  
Vol 67 ◽  
pp. 165
Author(s):  
Hossain Md Shahdat ◽  
Michio Hashimoto ◽  
Toshiko Hara ◽  
Suntio Masumura
Keyword(s):  
Fatty Acid ◽  
Platelet Aggregation ◽  
High Fat Diet ◽  
High Fat ◽  
Age Related
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