scholarly journals Understanding the Impact of Dietary Cholesterol on Chronic Metabolic Diseases through Studies in Rodent Models

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 939 ◽  
Author(s):  
Ángela Vinué ◽  
Andrea Herrero-Cervera ◽  
Herminia González-Navarro
Keyword(s):  
Metabolic Diseases ◽  
Low Density Lipoprotein ◽  
Dietary Cholesterol ◽  
Density Lipoprotein ◽  
Metabolic Complications ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Human Pathology ◽  
Key Factor ◽  
The Impact

The development of certain chronic metabolic diseases has been attributed to elevated levels of dietary cholesterol. However, decades of research in animal models and humans have demonstrated a high complexity with respect to the impact of dietary cholesterol on the progression of these diseases. Thus, recent investigations in non-alcoholic fatty liver disease (NAFLD) point to dietary cholesterol as a key factor for the activation of inflammatory pathways underlying the transition from NAFLD to non-alcoholic steatohepatitis (NASH) and to hepatic carcinoma. Dietary cholesterol was initially thought to be the key factor for cardiovascular disease development, but its impact on the disease depends partly on the capacity to modulate plasmatic circulating low-density lipoprotein (LDL) cholesterol levels. These studies evidence a complex relationship between these chronic metabolic diseases and dietary cholesterol, which, in certain conditions, might promote metabolic complications. In this review, we summarize rodent studies that evaluate the impact of dietary cholesterol on these two prevalent chronic diseases and their relevance to human pathology.

scholarly journals Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

2021 ◽  
Vol 22 (13) ◽  
pp. 6949
Author(s):  
Siarhei A. Dabravolski ◽  
Evgeny E. Bezsonov ◽  
Mirza S. Baig ◽  
Tatyana V. Popkova ◽  
Alexander N. Orekhov
Keyword(s):  
Heart Diseases ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Mitochondria ◽  
Atherogenic Dyslipidemia ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Mitochondrial Lipid ◽  
Cardioprotective Effects

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

scholarly journals Impact of raw cocoa and chocolate on lipid profile and liver function in alcohol-induced toxicity Wister rats

2017 ◽  
Vol 5 (2) ◽  
pp. 254
Author(s):  
Alaa Saleh ◽  
Murwan Sabahelkhier
Keyword(s):  
Fatty Liver ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Positive Control ◽  
Alcoholic Fatty Liver ◽  
Alcohol Group ◽  
High Doses ◽  
The Impact ◽  
Positive Controls

The aim of study is to evaluate the impact of raw cocoa and processed cocoa (galaxy chocolate) in the treatment of alcoholic fatty liver compare to prednisolone drug as common medication to treat fatty liver and carried out in Al-Neelain University in 2016. Eighteen female Wister rats were classified into six groups: Group one represented negative (H2O), Group two positive controls (0.5 ml/40% alcohol), Group three represented doses of 0.67g\kg raw cocoa, Group four represented dose of 1.35 g/kg raw cocoa, Group five represent dose of 5.4 g/kg galaxy chocolate, Group six received dose of 4.8 mg/kg prednisolone. The results show that the cocoa with low and high doses, galaxy chocolate and prednisolone significantly reduce the ALT, AST and GGT, and a significant decrease in the ALT level after administration of prednisolone drug when compared high cocoa dose group. Whereas, Galaxy chocolate significantly reduce the AST compared to low dose cocoa treated group. Also there is a significant increase in HDL and decrease in Total cholesterol, Triglycerol and low density lipoprotein in all treated groups compared to positive control. The ratio between Triglycerol: HDL and LDL: HDL show a significant reduction in group treated with galaxy chocolate compared to other treated groups. The results concluded that, cocoa in both forms raw and processed are efficient in the treatment of alcoholic fatty liver in comparison with prednisolone drug.

scholarly journals Cholesterol Homeostasis: An In Silico Investigation into How Aging Disrupts Its Key Hepatic Regulatory Mechanisms

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 314
Author(s):  
Amy Elizabeth Morgan ◽  
Mark Tomás Mc Auley
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Enzymatic Reactions ◽  
Low Density ◽  
Acetyl Coa ◽  
Alcoholic Fatty Liver ◽  
Age Related ◽  
Intracellular Cholesterol ◽  
The Impact

The dysregulation of intracellular cholesterol homeostasis is associated with several age-related diseases, most notably cardiovascular disease (CVD). Research in this area has benefitted from using computational modelling to study the inherent complexity associated with the regulation of this system. In addition to facilitating hypothesis exploration, the utility of modelling lies in its ability to represent an array of rate limiting enzymatic reactions, together with multiple feedback loops, which collectively define the dynamics of cholesterol homeostasis. However, to date no model has specifically investigated the effects aging has on this system. This work addresses this shortcoming by explicitly focusing on the impact of aging on hepatic intracellular cholesterol homeostasis. The model was used to investigate the experimental findings that reactive oxygen species induce the total activation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR). Moreover, the model explored the impact of an age-related decrease in hepatic acetyl-CoA acetyltransferase 2 (ACAT2). The model suggested that an increase in the activity of HMGCR does not have as significant an impact on cholesterol homeostasis as a decrease in hepatic ACAT2 activity. According to the model, a decrease in the activity of hepatic ACAT2 raises free cholesterol (FC) and decreases low-density lipoprotein cholesterol (LDL-C) levels. Increased acetyl CoA synthesis resulted in a reduction in the number of hepatic low-density lipoprotein receptors, and increased LDL-C, FC, and cholesterol esters. The rise in LDL-C was restricted by elevated hepatic FC accumulation. Taken together these findings have important implications for healthspan. This is because emerging clinical data suggest hepatic FC accumulation is relevant to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is associated with an increased risk of CVD. These pathophysiological changes could, in part, help to explain the phenomenon of increased mortality associated with low levels of LDL-C which have been observed in certain studies involving the oldest old (≥85 years).

Tamoxifen as an antioxidant and cardioprotectant

1995 ◽  
Vol 61 ◽  
pp. 209-219 ◽  
Author(s):  
Helen Wiseman
Keyword(s):  
Breast Cancer ◽  
Oxidative Damage ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Tamoxifen Treatment ◽  
Cholesterol Levels ◽  
Ldl Particles ◽  
Key Factor ◽  
Cardioprotective Action

Tamoxifen is widely used in the treatment of breast cancer and has been proposed as a prophylactic agent in this disease. Tamoxifen is an effective antioxidant and protects membranes and low-density lipoprotein (LDL) particles against oxidative damage. This antioxidant action is shared by endogenous and synthetic oestrogens. The ability of tamoxifen to protect LDL particles against the oxidative damage implicated in atherosclerosis may be an important factor in the reported cardioprotective action of tamoxifen in women being treated for breast cancer. In addition, tamoxifen has been found to act in a similar manner to oestrogens to lower plasma cholesterol levels. The cardioprotective action of tamoxifen may be a key factor in predicting the likely risk/benefit ratio for prophylactic tamoxifen treatment in otherwise healthy women, who have been calculated to be genetically predisposed to developing breast cancer. In the future, predisposition to breast cancer may be determined by genetic screening.

Molasses Increases HDL Cholesterol in Rats Research Note

2005 ◽  
Vol 75 (3) ◽  
pp. 211-217 ◽  
Author(s):  
Schlegelmilch ◽  
Brandsch ◽  
Stangl ◽  
Eder
Keyword(s):  
Dry Matter ◽  
Control Diet ◽  
Low Density Lipoprotein ◽  
Dietary Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Serum Lipoproteins ◽  
Cholesterol Levels

Two experiments were conducted to determine whether molasses might exert effects on serum lipoproteins. In experiment 1, 24 rats were divided into two groups and fed diets containing liquid molasses from sugar beet or sucrose (7.71 g of molasses dry matter or sucrose per kg of diet). The second experiment included four groups of rats (n = 12/group) and was conducted in a bifactorial design, with the factors being molasses (non-supplementation vs. supplementation of 77.1 g of molasses dry matter per kg of diet at the expense of sucrose) and dietary cholesterol (0 vs. 5 g/kg diet). In experiment 1, the ratio of low-density lipoprotein (LDL) to high-density lipoprotein (HDL) cholesterol concentration tended to be lower in rats fed the molasses diet than in rats fed the control diet (p < 0.15). In experiment 2, rats fed the molasses diet had higher concentrations of HDL cholesterol (+ 26%) than control rats fed diets without molasses (p < 0.05). This effect was independent of the dietary cholesterol concentration. Concentrations of cholesterol in LDL, very low-density lipoprotein (VLDL), and liver as well as concentrations of triacylglycerols in plasma and liver remained unaffected by molasses in both experiments. In conclusion, the results of this study suggest that supplementation of molasses is effective at raising HDL cholesterol levels in rats.

scholarly journals Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters

2019 ◽  
Vol 20 (14) ◽  
pp. 3515 ◽  
Author(s):  
Jinjie Wang ◽  
Kunxiang He ◽  
Chun Yang ◽  
Xiao Lin ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Dietary Cholesterol ◽  
Gene Mutations ◽  
Density Lipoprotein ◽  
Inherited Disease ◽  
Atherosclerotic Lesions ◽  
Cholesterol Levels

Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/− hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/− hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/− hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/− hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. Conclusions: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/− hamsters, suggesting that the LDLR+/− hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD.

Sterol metabolism in fetal, newborn, and suckled lambs and their response to cholesterol after weaning

1995 ◽  
Vol 269 (2) ◽  
pp. E331-E340 ◽  
Author(s):  
C. P. Cavender ◽  
S. D. Turley ◽  
J. M. Dietschy
Keyword(s):  
Metabolic Response ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Dietary Cholesterol ◽  
Density Lipoprotein ◽  
Cholesterol Concentration ◽  
Sterol Synthesis ◽  
Stages Of Development ◽  
Cholesterol Levels ◽  
Three Stages

Several aspects of cholesterol metabolism were studied in lambs at six stages of development. The first three stages involved fetal lambs with gestational ages (fertilization set at -150 days) of -73 days (early fetal), -42 days (midfetal), and -14 days (late fetal). The other groups comprised newborn (0 days), suckled (17 days), and weaned (105 days) lambs. The liver, kidney, spleen, and brain actively synthesized cholesterol at all stages of development, but hepatic synthesis in the suckled lambs was markedly suppressed compared with that in their newborn and weaned counterparts. Whereas intestinal sterol synthesis was very low in all the fetal lambs, the converse was true in the neonatal animals. The total cholesterol concentration in the liver, intestine, kidney, and spleen remained relatively constant at all stages of growth, whereas in brain tissue it increased throughout development. Plasma total and low-density-lipoprotein cholesterol levels were lowest in the late fetal lambs and highest in the suckled animals. The metabolic response of weaned lambs to a dietary cholesterol challenge was similar to that reported for various monogastric species.

Dyslipidemias and Microcirculation

2018 ◽  
Vol 24 (25) ◽  
pp. 2921-2926 ◽  
Author(s):  
Teresa Padró ◽  
Gemma Vilahur ◽  
Lina Badimon
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Microvascular Dysfunction ◽  
Inflammatory Cells ◽  
High Cholesterol ◽  
Cholesterol Levels ◽  
Enhanced Production ◽  
Preclinical Animal Models ◽  
The Impact ◽  
Myocardial Level

Dyslipidemia is widely accepted as one of the major risk factors in cardiovascular disease mainly due to its contribution in the pathogenesis of atherosclerosis in medium-sized and large arteries. However, it has become increasingly accepted that high-cholesterol levels can also adversely affect the microvasculature prior to the development of overt atherosclerosis. Moreover, hypercholesterolemia has shown, in preclinical animal models, to exert detrimental effects beyond the vascular tree leading to larger infarcts and adverse cardiac remodeling post-myocardial infarction. At a functional level, hypercholesterolemia has shown to impair endotheliumdependent vasodilation because on defects on nitric oxide bioavailability. The pathogenic mechanisms underlying microvascular dysfunction involve an enhanced arginase activity, enhanced production of free radicals and the activation, recruitment and accumulation of leukocytes, primarily neutrophils, via their diffusion through postcapillary venules. In turn, recruited inflammatory cells and certain inflammatory mediators enhance platelet adhesion, overall inducing a proinflammatory and prothrombotic phenotype. Within the present review, we aim to discuss the existing evidence regarding the presence of dyslipidemia - particularly high low density lipoprotein-cholesterol levels - and the occurrence of microvascular dysfunction, the mechanism by which high cholesterol levels induce functional alterations in the microvascular bed and, finally comment on the impact of dislipidemia-induced microvascular dysfunction at the myocardial level.

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