Dietary Cholesterol and Adrenal Regulation of Plasma Lipids

1958 ◽  
Vol 195 (1) ◽  
pp. 166-170 ◽  
Author(s):  
B. S. Powers ◽  
N. R. Di Luzio
Keyword(s):  
Significant Contribution ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Plasma Lipid ◽  
Plasma Phospholipid ◽  
Chow Diet ◽  
Lipid Levels ◽  
Purina Chow ◽  
Desoxycorticosterone Acetate

Adrenalectomized dogs maintained on desoxycorticosterone acetate manifest a progressive depletion of plasma phospholipid and cholesterol. Within a 4-week period a mean decrease of 60% is observed. The daily addition of cholesterol to the Purina chow diet prevented the hypolipemic response and resulted in significant elevation in the concentration of plasma cholesterol. The feeding of an identical amount of cholesterol to dogs with intact adrenals was not associated with any alteration in plasma lipid levels. The feeding of identical amounts of highly saturated fats or soya lecithin to adrenalectomized dogs resulted in the characteristic decline of plasma phospholipid and cholesterol. A significant contribution of the adrenal gland to the regulation of plasma lipid metabolism in normal and cholesterol-fed dogs is indicated.

Abstract P555: Plasma Lipids And The Risk For Stroke In The Reasons For Geographic And Racial Differences In Stroke Study (regards).

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Neil Zakai ◽  
Jessica Minnier ◽  
Monika M Safford ◽  
Lisandro Colantonio ◽  
Marguerite M Irvin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Racial Differences ◽  
Stroke Risk ◽  
Plasma Lipids ◽  
Cox Regression ◽  
Strong Association ◽  
Plasma Lipid ◽  
Lipid Levels ◽  
Cvd Risk ◽  
Stroke Incidence

Introduction: Whether plasma lipid levels are associated with stroke risk remains controversial, with even less data for American blacks versus whites. Hypothesis: We hypothesized that abnormal lipid levels are not associated with stroke incidence in either blacks or whites. Methods: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30,283 black and white individuals aged 45+ from the contiguous U.S. between 2003 to 2007, participants with a history of stroke at baseline were excluded. Participants were followed until 2018 for stroke events following the WHO definition and confirmed by review of medical records. The association of lipid measures with stroke were assessed using Cox regression models adjusted for traditional CVD risk factors and an age-x-race interaction term. Results: With 27,714 participants (mean age 64.85± 9.43, 59.5% white and 55.4% female), over a median of 11 years of follow up, 1,415 stroke events occurred, of which 599 among blacks. After adjusting for traditional stroke risk factors, there were modest associations between higher total cholesterol and higher LDL, but not higher triglycerides, with stroke risk. There was no evidence of a race interaction. Overall, HDL levels were not associated with stroke risk. However, when stratified by race, whites had a reduced risk of stroke with higher HDL-C, whereas no association was seen among blacks (p-interaction 0.09). Conclusion: In REGARDs, there was a modest association of cholesterol measures with stroke risk. The association for HDL with stroke may be influenced by race, with a less strong association among blacks than among whites.

scholarly journals Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Johanna P. van Geffen ◽  
Frauke Swieringa ◽  
Kim van Kuijk ◽  
Bibian M. E. Tullemans ◽  
Fiorella A. Solari ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Thrombus Formation ◽  
Plasma Cholesterol ◽  
Chow Diet ◽  
Wild Type ◽  
Fibrin Formation ◽  
Established Risk Factor ◽  
Arterial Thrombus ◽  
Normal Chow ◽  
Platelet Proteome

AbstractHyperlipidemia is a well-established risk factor for cardiovascular diseases. Millions of people worldwide display mildly elevated levels of plasma lipids and cholesterol linked to diet and life-style. While the prothrombotic risk of severe hyperlipidemia has been established, the effects of moderate hyperlipidemia are less clear. Here, we studied platelet activation and arterial thrombus formation in Apoe−/− and Ldlr−/− mice fed a normal chow diet, resulting in mildly increased plasma cholesterol. In blood from both knockout mice, collagen-dependent thrombus and fibrin formation under flow were enhanced. These effects did not increase in severe hyperlipidemic blood from aged mice and upon feeding a high-fat diet (Apoe−/− mice). Bone marrow from wild-type or Ldlr−/− mice was transplanted into irradiated Ldlr−/− recipients. Markedly, thrombus formation was enhanced in blood from chimeric mice, suggesting that the hyperlipidemic environment altered the wild-type platelets, rather than the genetic modification. The platelet proteome revealed high similarity between the three genotypes, without clear indication for a common protein-based gain-of-function. The platelet lipidome revealed an altered lipid profile in mildly hyperlipidemic mice. In conclusion, in Apoe−/− and Ldlr−/− mice, modest elevation in plasma and platelet cholesterol increased platelet responsiveness in thrombus formation and ensuing fibrin formation, resulting in a prothrombotic phenotype.

scholarly journals ILRUN , a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice

2020 ◽  
Vol 127 (11) ◽  
pp. 1347-1361 ◽  
Author(s):  
Xin Bi ◽  
Takashi Kuwano ◽  
Paul C. Lee ◽  
John S. Millar ◽  
Li Li ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver Transcriptome ◽  
Artery Disease

Rationale: Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated–like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. Objective: To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. Methods and Results: ILRUN encodes a protein that contains a ubiquitin-associated–like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun -deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated–like domain of ILRUN was found to be required for its interaction with PPARα. Conclusions: These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human.

scholarly journals (Pro)renin Receptor Inhibition Reduces Plasma Cholesterol and Triglycerides but Does Not Attenuate Atherosclerosis in Atherosclerotic Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Dien Ye ◽  
Xiaofei Yang ◽  
Liwei Ren ◽  
Hong S. Lu ◽  
Yuan Sun ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Inflammatory Responses ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Low Density ◽  
Beneficial Effects ◽  
Receptor Inhibition ◽  
Density Lipoprotein Receptor

Objective: Elevated plasma cholesterol concentrations contributes to ischemic cardiovascular diseases. Recently, we showed that inhibiting hepatic (pro)renin receptor [(P)RR] attenuated diet-induced hypercholesterolemia and hypertriglyceridemia in low-density lipoprotein receptor (LDLR) deficient mice. The purpose of this study was to determine whether inhibiting hepatic (P)RR could attenuate atherosclerosis.Approach and Results: Eight-week-old male LDLR−/− mice were injected with either saline or N-acetylgalactosamine-modified antisense oligonucleotides (G-ASOs) primarily targeting hepatic (P)RR and were fed a western-type diet (WTD) for 16 weeks. (P)RR G-ASOs markedly reduced plasma cholesterol concentrations from 2,211 ± 146 to 1,128 ± 121 mg/dL. Fast protein liquid chromatography (FPLC) analyses revealed that cholesterol in very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL)/LDL fraction were potently reduced by (P)RR G-ASOs. Moreover, (P)RR G-ASOs reduced plasma triglyceride concentrations by more than 80%. Strikingly, despite marked reduction in plasma lipid concentrations, atherosclerosis was not reduced but rather increased in these mice. Further testing in ApoE−/− mice confirmed that (P)RR G-ASOs reduced plasma lipid concentrations but not atherosclerosis. Transcriptomic analysis of the aortas revealed that (P)RR G-ASOs induced the expression of the genes involved in immune responses and inflammation. Further investigation revealed that (P)RR G-ASOs also inhibited (P)RR in macrophages and in enhanced inflammatory responses to exogenous stimuli. Moreover, deleting the (P)RR in macrophages resulted in accelerated atherosclerosis in WTD fed ApoE−/− mice.Conclusion: (P)RR G-ASOs reduced the plasma lipids in atherosclerotic mice due to hepatic (P)RR deficiency. However, augmented pro-inflammatory responses in macrophages due to (P)RR downregulation counteracted the beneficial effects of lowered plasma lipid concentrations on atherosclerosis. Our study demonstrated that hepatic (P)RR and macrophage (P)RR played a counteracting role in atherosclerosis.

scholarly journals Integrative genomic analysis identified common regulatory networks underlying the correlation between coronary artery disease and plasma lipid levels

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liuying Chen ◽  
Yinghao Yao ◽  
Chaolun Jin ◽  
Shen Wu ◽  
Qiang Liu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Plasma Lipids ◽  
Lipid Level ◽  
Plasma Lipid ◽  
Lipid Levels ◽  
Regulatory Relationship ◽  
Artery Disease

Abstract Background Coronary artery disease (CAD) and plasma lipid levels are highly correlated, indicating the presence of common pathways between them. Nevertheless, the molecular pathways underlying the pathogenic comorbidities for both traits remain poorly studied. We sought to identify common pathways and key driver genes by performing a comprehensive integrative analysis based on multi-omic datasets. Methods By performing a pathway-based analysis of GWAS summary data, we identified that lipoprotein metabolism process-related pathways were significantly associated with CAD risk. Based on LD score regression analysis of CAD-related SNPs, significant heritability enrichments were observed in the cardiovascular and digestive system, as well as in liver and gastrointestinal tissues, which are the main regulators for lipid level. Results We found there existed significant genetic correlation between CAD and other lipid metabolism related traits (the smallest P value < 1 × 10− 16). A total of 13 genes (e.g., LPA, APOC1, APOE and SLC22A3) was found to be overlapped between CAD and plasma lipid levels. By using the data-driven approach that integrated transcriptome information, we discovered co-expression modules associated prominently with both CAD and plasma lipids. With the detailed topology information on gene-gene regulatory relationship, we illustrated that the identified hub genes played important roles in the pathogenesis of CAD and plasma lipid turbulence. Conclusion Together, we identified the shared molecular mechanisms underlying the correlation between CAD and plasma lipid levels.

Fasting is not required for measuring plasma lipid levels in rabbits

2019 ◽  
Vol 54 (3) ◽  
pp. 272-280 ◽  
Author(s):  
Rong Wang ◽  
Ruihan Liu ◽  
Lu Li ◽  
Baoning Liu ◽  
Liang Bai ◽  
...  
Keyword(s):  
Corn Oil ◽  
Experimental Studies ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Diet Group ◽  
Lipoprotein Cholesterol ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Lipid Levels ◽  
Glucose Levels

Plasma lipid and glucose levels are important parameters for evaluating the onset and development of metabolic and cardiovascular diseases. In clinical and experimental studies of humans or mice, fasting is often required before testing plasma lipid and glucose levels. The rabbit is a valuable animal model for cardiovascular disease research. However, whether fasting is necessary for measuring plasma lipid and glucose levels in rabbits remains unclear. In the current study, 12 healthy Japanese white rabbits (males weighing 2.5–3.0 kg) were randomly divided into a chow diet group ( n = 6) and a high cholesterol diet group ( n = 6). They were fed either a standard chow diet or a chow diet supplemented with 0.5% cholesterol and 3% corn oil for 12 weeks. After 12 weeks, the plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and glucose were measured before and after various fasting durations (8, 12, 16, 20 and 24 h). The results showed that there were no significant differences in lipid levels between the fasting and non-fasting samples, whereas glucose levels were lower after 8 h of fasting than in the absence of fasting. Moreover, the glucose levels were restored to normal after 8 h of refeeding. These results indicate that fasting does not affect plasma lipid values in rabbits but that fasting is important for determining the glucose level in rabbits. These findings may be helpful for future rabbit experiments and beneficial for animal welfare.

scholarly journals Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonna Weisell ◽  
Anna-Kaisa Ruotsalainen ◽  
Juha Näpänkangas ◽  
Matti Jauhiainen ◽  
Jaana Rysä
Keyword(s):  
Aortic Valve ◽  
Body Weight Gain ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Hepatic Tissue ◽  
Lipid Levels ◽  
Calcific Aortic Valve Disease ◽  
Beneficial Effects ◽  
Valvular Calcification ◽  
Cytokines And Chemokines

AbstractIn calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD. LDLr−/−ApoB100/100 male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemic LDLr−/− ApoB100/100 mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.

scholarly journals Effects of inulin-type fructans on lipid metabolism in man and in animal models

2005 ◽  
Vol 93 (S1) ◽  
pp. S163-S168 ◽  
Author(s):  
Michel Beylot
Keyword(s):  
Propionic Acid ◽  
Acid Metabolism ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Selective Exposure ◽  
Bile Acid Metabolism ◽  
Lipid Levels ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
The Difference

Studies in rodents show that inulin and oligofructose can reduce the plasma levels of cholesterol and triacylglycerols (TG). In addition, they can oppose TG accumulation in liver and have favourable effects on hepatic steatosis. The hypotriglyceridaemic effect is due to a reduction in hepatic re-esterification of fatty acids, but mainly in the expression and activity of liver lipogenesis, resulting in lower hepatic secretion rate of TG. This repression of lipogenesis is not observed in adipose tissue. The effect on liver lipogenesis can be explained by reduced insulin/glucose levels or by a selective exposure of the liver to increased amounts of propionic acid produced in the large intestine during fermentation of non-digestible carbohydrates. The decrease in plasma cholesterol could also be due to inhibition of cholesterol synthesis by propionic acid or to modifications in the bile acid metabolism. Studies in man yield more conflicting results with a decrease or no effects on plasma lipid levels, and, when a decrease is observed, more marked effects on TG than on cholesterol and more consistent action of inulin than of oligofructose. Besides the difference in the dose of inulin or oligofructose used, differences in metabolic status could play a role in this discrepancy between man and animals since reduction in plasma TG is observed in man mainly in a situation of increased liver lipogenesis (high-carbohydrate diet, obesity, hypertriglyceridaemia). The effects on plasma cholesterol appear also more marked in hyperlipidaemic subjects than in healthy controls, suggesting that inulin and oligofructose have beneficial effects in these types of subjects.

scholarly journals Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients

2002 ◽  
Vol 43 (8) ◽  
pp. 1170-1180 ◽  
Author(s):  
Joel D. Morrisett ◽  
Ghada Abdel-Fattah ◽  
Ron Hoogeveen ◽  
Eddie Mitchell ◽  
Christie M. Ballantyne ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Renal Transplant ◽  
Lipase Activity ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Transplant Rejection ◽  
Plasma Lipid ◽  
Immunosuppressive Drug ◽  
Transplant Patients ◽  
Renal Transplant Patients

Sirolimus (Rapammune®, rapamycin, RAPA) is a potent immunosuppressive drug that reduces renal transplant rejection. Hyperlipidemia is a significant side effect of sirolimus treatment, and frequently leads to cardiovascular disease. This study was undertaken to determine the repeatability, reversibility, and dose dependence of the plasma lipid and apolipoprotein altering effects of sirolimus, and to elucidate the mechanism by which sirolimus induces hypertriglyceridemia in some renal transplant patients. Six patients with renal allografts maintained on cyclosporine A and prednisone were selected on the basis of their previous hyperlipidemic response to short term (14 days) sirolimus administration. For longer-term treatment, each patient was started on 10 mg/day sirolimus and continued as tolerated for 42 days to reinduce hyperlipidemia. Timed blood samples were analyzed for lipid, apolipoprotein, and sirolimus levels. During sirolimus administration, mean total plasma cholesterol increased from 214 mg/dl to 322 mg/dl (+50%; range 25–92%); LDL-cholesterol levels followed a similar pattern. Mean triglyceride level rose from 227 to 432 mg/dl (+95%; range 9–254%). ApoB-100 concentration rose from 124 to 160 mg/dl (+28%; P < 0.05). ApoC-III level increased from 28.9 to 55.5 mg/dl, +92%; (P < 0.013). These lipid and apolipoprotein changes were found to be repeatable, reversible, and dose dependent. [13C4]palmitate metabolic studies in four patients with hypertriglyceridemia indicated that the free fatty acid pool was expanded by sirolimus treatment (mean = 42.3%). Incorporation of [13C4]palmitate into triglycerides of VLDL, IDL, and LDL was decreased 38.3%, 42,1%, and 38.4%, respectively, by sirolimus treatment of these patients.These results suggest that sirolimus alters the insulin signaling pathway so as to increase adipose tissue lipase activity and/or decrease lipoprotein lipase activity, resulting in increased hepatic synthesis of triglyceride, increased secretion of VLDL, and increased hypertriglyceridemia.

Sign in / Sign up

Export Citation Format

Share Document