scholarly journals Albino mice with the point mutation at the tyrosinase locus show high cholesterol diet-induced NASH susceptibility

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaushalya Kulathunga ◽  
Arata Wakimoto ◽  
Yukiko Hiraishi ◽  
Manoj Kumar Yadav ◽  
Kyle Gentleman ◽  
...  
Keyword(s):  
Point Mutation ◽  
Genetic Difference ◽  
Elevated Serum ◽  
Serum Lipoprotein ◽  
Normal Diet ◽  
Lipid Absorption ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Alcoholic Fatty Liver

AbstractNon-alcoholic fatty liver disease (NAFLD) constitutes a metabolic disorder with high worldwide prevalence and increasing incidence. The inflammatory progressive state, non-alcoholic steatohepatitis (NASH), leads to liver fibrosis and carcinogenesis. Here, we evaluated whether tyrosinase mutation underlies NASH pathophysiology. Tyrosinase point-mutated B6 (Cg)-Tyrc-2J/J mice (B6 albino) and C57BL/6J black mice (B6 black) were fed with high cholesterol diet (HCD) for 10 weeks. Normal diet-fed mice served as controls. HCD-fed B6 albino exhibited high NASH susceptibility compared to B6 black, a phenotype not previously reported. Liver injury occurred in approximately 50% of B6 albino from one post HCD feeding, with elevated serum alanine aminotransferase and aspartate aminotransferase levels. NASH was induced following 2 weeks in severe-phenotypic B6 albino (sB6), but B6 black exhibited no symptoms, even after 10 weeks. HCD-fed sB6 albino showed significantly higher mortality rate. Histological analysis of the liver revealed significant inflammatory cell and lipid infiltration and severe fibrosis. Serum lipoprotein analysis revealed significantly higher chylomicron and very low-density lipoprotein levels in sB6 albino. Moreover, significantly higher small intestinal lipid absorption and lower fecal lipid excretion occurred together with elevated intestinal NPC1L1 expression. As the tyrosinase point mutation represents the only genetic difference between B6 albino and B6 black, our work will facilitate the identification of susceptible genetic factors for NASH development and expand the understanding of NASH pathophysiology.

Effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study

2003 ◽  
Vol 95 (3) ◽  
pp. 1194-1200 ◽  
Author(s):  
Ai-Lun Yang ◽  
Chauying J. Jen ◽  
Hsiun-ing Chen
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Vascular Function ◽  
Time Course ◽  
Early Stage ◽  
Elevated Serum ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol

It is plausible to assume that exercise training, when applied early enough, can completely correct atherosclerotic defects. Using rabbit aortic specimens, we examined the effects of chronic exercise and high-cholesterol diet feeding on vascular function for different time periods. Male New Zealand White rabbits were divided into four groups: the normal diet groups with or without exercise training and the high-cholesterol diet groups with or without exercise training. Animals in high-cholesterol diet groups were fed 2% cholesterol rabbit chow for 2, 4, or 6 wk. Those in exercise training groups ran on a treadmill at 0.88 km/h for up to 40 min/day, 5 days/wk for the same period of time as the diet feeding. Thoracic aortas were isolated for functional and immunohistochemical analyses. We found that 1) although high-cholesterol diet feeding (≥2 wk) elevated serum cholesterol levels and impaired acetylcholine-evoked vasorelaxation, only the latter effect was reversed by exercise training; 2) the effects of diet and exercise on acetylcholine-evoked vasorelaxation were mainly due to altered release of nitric oxide and endothelium-derived hyperpolarizing factor; and 3) diet feeding for 4 or 6 wk caused significant lipid deposition and expression of P-selectin, VCAM-1, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, which were largely reduced by exercise training. In conclusion, parallel exercise training almost completely reverses the early-stage endothelial dysfunction caused by high-cholesterol diet feeding.

SHORT TERM HIGH CHOLESTEROL DIET CAUSES CHANGES IN MEGAKARYOCYTE SIZE AND IN VASCULAR ULTRASTRUCTURE

1987 ◽  
Author(s):  
S Dalby Kristensen ◽  
K M Roberts ◽  
J Lawry ◽  
J F Martin
Keyword(s):  
Smooth Muscle ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Short Term ◽  
Transmission Electron ◽  
Perfusion Fixation ◽  
And Migration ◽  
Proliferation And Migration

Platelets produced by megakaryocytes (MK) have a role in atherogenesis. Six pairs of male litter mate rabbits were randomised to feeding with either 2g of cholesterol daily in addition to their normal diet or normal diet alone. After seven days the animals were killed and serum cholesterol, platelet count, MK total, cytoplasmic and nuclear area (microscopic planimetry) and MK DNA content cell distribution (fluorescent activated cell sorting) were measured and compared between the two groups. The results are given in the table as medians with range values in brackets.After perfusion-fixation the aortas were examined by transmission electron microscopy. In the aortas from the animals on high cholesterol diet cells with ultrastructural features resembling smooth muscle cells were found in the intima. Changes in megakaryocyte size are associated with the occurrence of smooth muscle cell proliferation and migration. The platelet-megakaryocyte axis may be activated in early atherogenesis.

Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction

2009 ◽  
Vol 296 (5) ◽  
pp. H1281-H1288 ◽  
Author(s):  
Karen Y. Stokes ◽  
Tammy R. Dugas ◽  
Yaoping Tang ◽  
Harsha Garg ◽  
Eric Guidry ◽  
...  
Keyword(s):  
Drinking Water ◽  
Endothelial Dysfunction ◽  
Leukocyte Adhesion ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Cytoprotective Activity ◽  
Reactive Protein ◽  
Microvascular Inflammation

The nitrite anion is an endogenous product of mammalian nitric oxide (NO) metabolism, a key intermediate in the nitrogen cycle in plants, and a constituent of many foods. Research over the past 6 years has revealed surprising biological and cytoprotective activity of this anion. Hypercholesterolemia causes a proinflammatory phenotype in the microcirculation. This phenotype appears to result from a decline in NO bioavailability that results from a reduction in NO biosynthesis, inactivation of NO by superoxide, or both. Since nitrite has been shown to be potently cytoprotective and restore NO biochemical homeostasis, we investigated if supplemental nitrite could attenuate microvascular inflammation caused by a high cholesterol diet. C57Bl/6J mice were fed either a normal diet or a high cholesterol diet for 3 wk to induce microvascular inflammation. Mice on the high cholesterol diet received either nitrite-free drinking water or supplemental nitrite at 33 or 99 mg/l ad libitum in their drinking water. The results from this investigation reveal that mice fed a cholesterol-enriched diet exhibited significantly elevated leukocyte adhesion to and emigration through the venular endothelium as well as impaired endothelium-dependent relaxation in arterioles. Administration of nitrite in the drinking water inhibited the leukocyte adhesion and emigration and prevented the arteriolar dysfunction. This was associated with sparing of reduced tetrahydrobiopterin and decreased levels of C-reactive protein. These data reveal novel anti-inflammatory properties of nitrite and implicate the use of nitrite as a new natural therapy for microvascular inflammation and endothelial dysfunction associated with hypercholesterolemia.

scholarly journals A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins

2021 ◽  
Vol 43 (2) ◽  
pp. 818-830
Author(s):  
Alkistis Kapelouzou ◽  
Michalis Katsimpoulas ◽  
Christos Kontogiannis ◽  
Irene Lidoriki ◽  
Georgios Georgiopoulos ◽  
...  
Keyword(s):  
Normal Diet ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Control Groups ◽  
Reverse Transcription Pcr ◽  
Rabbit Myocardium ◽  
Normal Chow ◽  
Polymerase Chain

Background: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. Methods: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. Results: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. Conclusions: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

scholarly journals Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 445
Author(s):  
Yang Deng ◽  
Ji Ma ◽  
Xin Weng ◽  
Yuqin Wang ◽  
Maoru Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Zebrafish Model ◽  
Alcoholic Fatty Liver ◽  
Larval Zebrafish

NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while H2O2 was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40μM) and in vitro (K3O, 20μM). Additionally, K3O (40μM) reduced neutrophil aggregation in vivo. K3O (20μM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and H2O2-exposed HepG2 cells. In the mechanism study, keap1, nrf2, tnf-α, and il-6 mRNA were all significantly reversed by K3O (20μM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in H2O2-exposed HepG2 cells after they were treated with K3O (20μM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model.

Bifidobacterium adolescentis and Lactobacillus rhamnosus alleviate non-alcoholic fatty liver disease induced by a high-fat, high-cholesterol diet through modulation of different gut microbiota-dependent pathways

2020 ◽  
Vol 11 (7) ◽  
pp. 6115-6127
Author(s):  
Gang Wang ◽  
Ting Jiao ◽  
Yue Xu ◽  
Daozheng Li ◽  
Qian Si ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

B. adolescentis and L. rhamnosus alleviate non-alcoholic fatty liver disease induced by a high-fat, high-cholesterol diet through modulation on different gut microbiota-dependent pathways. The SCFAs are important participants.

scholarly journals The Effect of Aqueous Extract of Vernonia Amygdalina (Bitter Leaf) on Antioxidants and the Liver of Rabbits on High Cholesterol Diet

2020 ◽  
pp. 91-100
Author(s):  
O. Abdulmalik ◽  
O. O. Oladapo
Keyword(s):  
Superoxide Dismutase ◽  
Aqueous Extract ◽  
Fatty Infiltration ◽  
Atherogenic Diet ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Aspartate Transaminase ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Significant Difference

Aims: To determine the effect of V. amygdalina on the levels of antioxidants and the liver of rabbits fed on a atherogenic diet. Study Design: Prospective experimental study. Place and Duration of study: Study lasted 14 weeks at Department of Anatomy, University of Ibadan, Nigeria. Methodology: Eighteen male rabbits were randomly divided into three groups comprising control, high cholesterol diet and high cholesterol diet plus 200mg/kg of aqueous extract of V. amygdalina. The animals were fed a normal animal chow, or a diet supplemented by 0.5% cholesterol and 1% methionine for twelve weeks. Subsequently, serum was obtained for liver function tests. Samples of the liver of the animals were obtained for antioxidant tests and histology. Results: Aspartate transaminase was significantly elevated in atherogenic diet only group compared to animals on normal diet. There was also no statistically significant difference across the three groups in the alanine transaminase values. Superoxide dismutase were significantly reduced in animals that were administered extract. Malondialdehyde was not statistically different across the three groups. The histology of the liver of the animals on high cholesterol diet (with and without extract administration) revealed similar microscopic presence of fatty infiltration of the liver. Conclusion: The use of high cholesterol diet for a duration of twelve weeks in rabbits resulted in significant increased relative liver weight, aspartate transaminase, superoxide dismutase and hepatic microvesicular steatosis. Furthermore, the use of 200mg/kg of aqueous extract of V. amygdalina had ameliorative effect on the level of superoxide dismutase. It did not have a measurable effect on the malondialdehyde, liver enzymes and liver histology.

scholarly journals The Effect of Ilex × meserveae S. Y.Hu Extract and Its Fractions on Renal Morphology in Rats Fed with Normal and High-Cholesterol Diet

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 818
Author(s):  
Piotr Kuropka ◽  
Anna Zwyrzykowska-Wodzińska ◽  
Robert Kupczyński ◽  
Maciej Włodarczyk ◽  
Antoni Szumny ◽  
...  
Keyword(s):  
Protective Role ◽  
Normal Diet ◽  
Ilex Paraguariensis ◽  
High Cholesterol Diet ◽  
Yerba Mate ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Natural Medicine ◽  
Filtration Barrier ◽  
The Impact

Therapeutic properties of Ilex species are widely used in natural medicine. Ilex × meserveae may become a potential substitute for Ilex paraguariensis (Yerba Mate). As a part of the preliminary safety verification of this European Ilex hybrid vs. Yerba Mate, an eight-week study concerning the impact of regular administration of leaves of both species on kidneys was conducted. The standard water infusion and three dominant fractions of Ilex × meserveae leaves’ constituents (polyphenols, saponins and less polar terpenoids) were separately tried on 96 male Wistar rats divided into 8-member groups. Animals were divided into two basic nutritional groups: the first one was rats fed standard feed and the second on was rats fed with high-cholesterol diet (20 g of cholesterol per kg of standard feed). Postmortem morphometric evaluation of stained kidney samples concerned the filtration barrier elements, which are crucial in proper diuresis. The results showed that saponins present in the hydroalcoholic dry extract (administered in a dose of 10 mg/kg of body weight/day) as well as in water infusions (1:20) from Ilex × meserveae and Ilex paraguariensis do not demonstrate nephrotoxicity but conversely, have a protective role on kidney status in animals fed with a normal diet and in a high-cholesterol diet.

scholarly journals Hepatic lipase deficiency produces glucose intolerance, inflammation and hepatic steatosis

2015 ◽  
Vol 227 (3) ◽  
pp. 179-191 ◽  
Author(s):  
Irene Andrés-Blasco ◽  
Andrea Herrero-Cervera ◽  
Ángela Vinué ◽  
Sergio Martínez-Hervás ◽  
Laura Piqueras ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Glucose Intolerance ◽  
Hepatic Lipase ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Obese People ◽  
Alcoholic Fatty Liver

Metabolic syndrome and type 2 diabetes mellitus constitute a major problem to global health, and their incidence is increasing at an alarming rate. Non-alcoholic fatty liver disease, which affects up to 90% of obese people and nearly 70% of the overweight, is commonly associated with MetS characteristics such as obesity, insulin resistance, hypertension and dyslipidemia. In the present study, we demonstrate that hepatic lipase (HL)-inactivation in mice fed with a high-fat, high-cholesterol diet produced dyslipidemia including hypercholesterolemia, hypertriglyceridemia and increased non-esterified fatty acid levels. These changes were accompanied by glucose intolerance, pancreatic and hepatic inflammation and steatosis. In addition, compared with WT mice, HL−/− mice exhibited enhanced circulating MCP1 levels, monocytosis and higher percentage of CD4+Th17+ cells. Consistent with increased inflammation, livers from HL−/− mice had augmented activation of the stress SAPK/JNK- and p38-pathways compared with the activation levels of the kinases in livers from WT mice. Analysis of HL−/− and WT mice fed regular chow diet showed dyslipidemia and glucose intolerance in HL−/− mice without any other changes in inflammation or hepatic steatosis. Altogether, these results indicate that dyslipidemia induced by HL-deficiency in combination with a high-fat, high-cholesterol diet promotes hepatic steatosis and inflammation in mice which are, at least in part, mediated by the activation of the stress SAPK/JNK- and p38-pathways. Future studies are warranted to asses the viability of therapeutic strategies based on the modulation of these kinases to reduce hepatic steatosis associated to lipase dysfunction.

Sign in / Sign up

Export Citation Format

Share Document