scholarly journals A High-Fat Diet Exacerbates the Course of Experimental Trypanosoma cruzi Infection That Can Be Mitigated by Treatment with Simvastatin

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Débora Maria Soares de Souza ◽  
Guilherme de Paula Costa ◽  
Ana Luísa Junqueira Leite ◽  
Daniela Silva de Oliveira ◽  
Kelerson Mauro de Castro Pinto ◽  
...  

The protozoan Trypanosoma cruzi is responsible for triggering a damage immune response in the host cardiovascular system. This parasite has a high affinity for host lipoproteins and uses the low-density lipoprotein (LDL) receptor for its invasion. Assuming that the presence of LDL cholesterol in tissues could facilitate T. cruzi proliferation, dietary composition may affect the parasite-host relationship. Therefore, the aim of this study was to evaluate myocarditis in T. cruzi-infected C57BL/6 mice—acute phase—fed a high-fat diet and treated with simvastatin, a lipid-lowering medication. Animals (n=10) were infected with 5×103 cells of the VL-10 strain of T. cruzi and treated or untreated daily with 20 mg/kg simvastatin, starting 24 h after infection and fed with a normolipidic or high-fat diet. Also, uninfected mice, treated or not with simvastatin and fed with normolipidic or high-fat diet, were evaluated as control groups. Analyses to measure the production of chemokine (C-C motif) ligand 2 (CCL2), interferon- (IFN-) γ, interleukin- (IL-) 10, and tumor necrosis factor (TNF); total hepatic lipid dosage; cholesterol; and fractions, as well as histopathological analysis, were performed on day 30 using cardiac and fat tissues. Our results showed that the high-fat diet increased (i) parasite replication, (ii) fat accumulation in the liver, (iii) total cholesterol and LDL levels, and (iv) the host inflammatory state through the production of the cytokine TNF. However, simvastatin only reduced the production of CCL2 but not that of other inflammatory mediators or biochemical parameters. Together, our data suggest that the high-fat diet may have worsened the biochemical parameters of the uninfected and T. cruzi-infected animals, as well as favored the survival of circulating parasites.

2018 ◽  
Vol 19 (12) ◽  
pp. 3903 ◽  
Author(s):  
Xiaofei Zhu ◽  
Jingyi Yang ◽  
Wenjuan Zhu ◽  
Xiaoxiao Yin ◽  
Beibei Yang ◽  
...  

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1—a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.


2021 ◽  
Vol 10 (18) ◽  
Author(s):  
Feroz Ahmad ◽  
Robert D. Mitchell ◽  
Tom Houben ◽  
Angela Palo ◽  
Tulasi Yadati ◽  
...  

Background We have shown previously that low‐density lipoprotein (LDL) can be oxidized in the lysosomes of macrophages, that this oxidation can be inhibited by cysteamine, an antioxidant that accumulates in lysosomes, and that this drug decreases atherosclerosis in LDL receptor–deficient mice fed a high‐fat diet. We have now performed a regression study with cysteamine, which is of more relevance to the treatment of human disease. Methods and Results LDL receptor–deficient mice were fed a high‐fat diet to induce atherosclerotic lesions. They were then reared on chow diet and drinking water containing cysteamine or plain drinking water. Aortic atherosclerosis was assessed, and samples of liver and skeletal muscle were analyzed. There was no regression of atherosclerosis in the control mice, but cysteamine caused regression of between 32% and 56% compared with the control group, depending on the site of the lesions. Cysteamine substantially increased markers of lesion stability, decreased ceroid, and greatly decreased oxidized phospholipids in the lesions. The liver lipid levels and expression of cluster of differentiation 68, acetyl–coenzyme A acetyltransferase 2, cytochromes P450 (CYP)27, and proinflammatory cytokines and chemokines were decreased by cysteamine. Skeletal muscle function and oxidative fibers were increased by cysteamine. There were no changes in the plasma total cholesterol, LDL cholesterol, high‐density lipoprotein cholesterol, or triacylglycerol concentrations attributable to cysteamine. Conclusions Inhibiting the lysosomal oxidation of LDL in atherosclerotic lesions by antioxidants targeted at lysosomes causes the regression of atherosclerosis and improves liver and muscle characteristics in mice and might be a promising novel therapy for atherosclerosis in patients.


2014 ◽  
Vol 395 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Vijayabaskar Pandian ◽  
Natarajan Aravindan ◽  
Sethupathy Subramanian ◽  
Somasundaram T. Somasundaran

Abstract Identifying pharmacologically safe lipid-lowering ‘deliverables’ could potentiate therapeutic outcome for diet-induced atherogenesis. Accordingly, we investigated the potential of molluscan (Katelysia opima) glycosaminoglycan (GAG) in modulating the early lipid changes in atherogenesis. Wistar rats were fed a diet with (n=24) or without (n=6) hypercholesterolemic atherogenic CCT (rat chow supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) for 17 days. CCT-fed rates were (i) treated with isolated molluscan GAG (40 mg/kg/day, s.c.) for 10 days after the introduction of CCT diet, (ii) cotreated with GAG (40 mg/kg/day, s.c.) for 17 days, or (iii) treated with heparin (200 units/kg/day, s.c.) for 10 days after the introduction of CCT. The increases induced by CCT diet in the plasma levels of cholesterol, triglycerides, high-density lipoprotein, very-low-density lipoprotein, and low-density lipoprotein were completely attenuated with GAG treatment. Consistently, alterations induced by CCT diet in the levels of plasma lecithin cholesterol acyltransferase and lipoprotein lipase activities were restored to baseline levels with GAG treatment. Coherently, histology revealed a decrease associated with GAG treatment in the CCT-diet-induced foam cells (in aorta), tubular damages (kidney), and lipid accumulations (liver). Together, these results suggest that GAG may exert antiatherogenesis potential by significantly attenuating lipid modulations derived by a high-fat diet. Further, the data imply that the GAG extracts may comprehensively prevent hypercholesterolemia-associated tissue damage and could thus serve as a therapeutic deliverable for hypercholesterolemia.


2019 ◽  
Vol 23 ◽  
pp. 100344
Author(s):  
Kenichi Kitamura ◽  
Kikuo Isoda ◽  
Koji Akita ◽  
Katsutoshi Miyosawa ◽  
Tomoyasu Kadoguchi ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2837 ◽  
Author(s):  
Beom-Rak Choi ◽  
Hyun-Jee Kim ◽  
Young-Joon Lee ◽  
Sae-Kwang Ku

The present study examined the effects of Wasabi leaf (WL) on 45% Kcal high-fat diet (HFD)-fed mild diabetic obese mice. In particular, the hepatoprotective (i.e., liver weight, histopathology of liver, serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase) effects of 12 weeks of continuous oral administration of 250 mg/kg metformin, and 200, 100, or 50 mg/kg WL were investigated. In addition, the hypolipidemic (i.e., serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein levels), hypoglycemic (i.e., glycated hemoglobin, blood glucose and insulin levels, pancreatic weight, and immunohistochemical-histopathological analysis of the pancreas), and anti-obesity effects (i.e., body weight, mean food consumption, total and abdominal body fat mass, periovarian fat weight, and histopathology of the periovarian and abdominal wall adipocytes) were monitored. The liver and general antioxidant defense systems were also assessed by lipid metabolism-related gene expression. All diabetes manifestations and related complications, including obesity and non-alcoholic fatty liver disease (NAFLD), were dose-dependently reduced after 84 days of oral treatment with metformin or each of the three dosages of WL. In particular, 50 mg/kg WL showed effective suppression effects against HFD-induced diabetes and related complications of obesity, NAFLD, and hyperlipidemia, comparable to the effects of metformin.


2017 ◽  
Vol 16 (10) ◽  
pp. 2417-2423
Author(s):  
Aqsa Ashfaq ◽  
Arif-ullah Khan ◽  
Amber Mahmood Minhas ◽  
Tahir Aqeel ◽  
Asaad M. Assiri ◽  
...  

Purpose: To investigate the anti-hyperlipidemic effect of Caralluma edulis and  Verbena officinalis.Methods: Phytochemical analysis of crude extracts of Caralluma edulis (Ce.Cr) and Verbena officinalis (Vo.Cr) were carried out. Hyperlipidemia was induced in mice with high-fat diet (HFD, 1.25 % w/w cholesterol, 0.5 % w/w cholic acid and 10 % v/w coconut oil). All the groups, except the saline-treated group, were fed on HFD for 4 weeks (lead-in period) to induce hyperlipidemia. Thereafter, the groups were treated with varying doses of the plant extract for 2 weeks (treatment period) as well as atorvastatin (10 mg/kg) reference standard. Body weight was measured fortnightly for all groups. Total cholesterol (TC), triglyceride (TGs) and low density lipoprotein (LDL) were assayed using Merck diagnostic kits. For histopathological analysis, liver slices were fixed in 10 % formalin and embedded in paraffin wax and was examined with the aid of hematoxylin and eosin staining (H & E).Results: Caralluma edulis (Ce.Cr) contains saponins, alkaloids, tannins, phenol, glycosides, terpenoids and flavonoids while Verbena officinalis (Vo.Cr) tested  positive for the presence of alkaloids, carbohydrates, flavonoids, saponins and tannins. HFD increased total cholesterol (TC), triglyceride (TGs), low density  lipoprotein (LDL) and very low density lipoprotein (VLDL) compared to regulator diet (p < 0.001). Treatment of the animals with Ce.Cr and Vo.Cr dose-dependently (500 - 1000 mg/kg) reduced serum TC, TGs, LDL and VLDL (p < 0.05, p < 0.01, p < 0.001, vs. HFD group) and raised high density lipoprotein (HDL) (p < 0.01, vs. HFD group), similar to that observed with atorvastatin (10 mg/kg). The  anti-hyperlipidemic effects of Ce.Cr and Vo.Cr were also confirmed via liver  histopathology results, showing improved structure with no hepatocellular necrosis and fat accumulation.Conclusion: These results indicate that Caralluma edulis and Verbena officinalis  exhibit antihyperlipidemic effect; thus, the plants have therapeutic potentials for the management of lipid disorders.Keywords: Caralluma edulis, Verbena officinalis, Anti-hyperlipidemia,   Hepatocellular necrosis


Foods ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 231
Author(s):  
Ji Eun Kim ◽  
Ji Yeon Lee ◽  
Chang-Ho Kang

Hyperglycemia due to uncontrolled glucose regulation is widely known as cause of diabetes, non-alcoholic fatty liver disease (NAFLD), and other complications. NAFLD refers to a condition in which fat is excessively accumulated, whether inflamed or not, and has caused serious medical problems in recent years. The aim of this study was to explore the antihyperglycemia effects of Limosilactobacillus fermentum MG4295 (L. fermentum MG4295) in high-fat diet (HFD)-induced in vivo. We demonstrated the suitability of L. fermentum MG4295 as a probiotic by observing its stability, survivability, and proliferation under simulated gastrointestinal conditions, and safety, antibiotic susceptibility, hemolysis, and enzyme activity. The potential antihyperglycemic activity of L. fermentum MG4295 was investigated in an HFD and sugar-water-induced mouse model. Administration of this strain for 12 weeks showed an improved trend in glucose tolerance, insulin, alanine amino transferase, total cholesterol, low-density lipoprotein cholesterol, and glucagon-like peptide-1. Histopathological analysis revealed that L. fermentum MG4295 significantly reduced the histopathological scores of hepatic steatosis, inflammation, and hepatocellular hypertrophy in liver tissues and lipid content in adipose tissues. Administration of L. fermentum MG4295 upregulated IRS-1, AKT, and GLUT4 and downregulated G6Pc and PEPCK expression in liver and/or muscle tissues. Our results suggest that L. fermentum MG4295 can improve hyperglycemia. Furthermore, it can be used as a dietary functional supplement to manage blood glucose.


2019 ◽  
Vol 20 (10) ◽  
pp. 1029-1040 ◽  
Author(s):  
Xinjie Lu

Background:One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy.Methods:We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis.Results:New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis.Conclusion:PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.


2019 ◽  
Vol 10 (2) ◽  
pp. 1181-1184
Author(s):  
Satheesh Naik K ◽  
Gurushanthaiah M ◽  
Nagesh Raju G ◽  
Lokanadham S ◽  
Seshadri Reddy V

Eclipta Alba has been used in traditional and folklore medicine to treat Hyperlipidemia and hepatic disorders. The present study was aimed to investigate the Antihyperlipidemic and hepatoprotective potentials of Eclipta Alba in high-fat diet -induced Albino rats and to determine the underlying mechanism.  A total of 30 adult albino rats of Wistar strain weighing 165–215 g were utilized. Animals were treated with high-fat diet for 8 weeks followed by post-treatment of E. Alba for 1 week, 2 weeks, and 3 weeks, respectively. After 12 h of fasting on the last day of the experiment, serum blood samples were collected in EDTA vials and processed for biochemical analysis.  A significant decrease in levels of total cholesterol and triglycerides was noted on animals treated with E. alba compared to high-fat diet animals. Treatment of hypercholesterolemic rats with E. Alba showed a marked decrease of serum low-density lipoprotein (LDL) and very LDL cholesterol concentrations compared to the hypercholesterolemic rats. High-fat diet feeding worsened the levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase enzymes, whereas the same markers were significantly improved by supplementation with E. alba compared to the normal group.  E. alba acts as an antihyperlipidemic agent in hyperlipidemic conditions and helps for better health.


Sign in / Sign up

Export Citation Format

Share Document