scholarly journals Sex hormones affect endothelial lipase-mediated lipid metabolism and atherosclerosis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Chuan Wang ◽  
Manabu Niimi ◽  
Shuji Kitajima ◽  
Fumikazu Matsuhisa ◽  
Haizhao Yan ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Plasma Lipids ◽  
Lipoprotein Metabolism ◽  
Lesion Size ◽  
Lipid Lowering ◽  
Endothelial Lipase ◽  
Chow Diet ◽  
Functional Roles ◽  
Hepatic Expression ◽  
Before And After

Abstract Background Endothelial lipase (EL) plays an important role in lipoprotein metabolism and atherosclerosis. To study the functional roles of EL, we recently generated transgenic (Tg) rabbits and reported that increased hepatic expression of EL in male Tg rabbits significantly reduced diet-induced hypercholesterolemia compared with non-Tg controls. This gender difference suggests that sex hormones may mediate EL functions thereby influencing lipoprotein metabolism. To examine this hypothesis, we compared the effects of orchiectomy and ovariectomy on plasma lipids and diet-induced atherosclerosis in both Tg and non-Tg rabbits. Methods Male rabbits were under orchiectomy whereas female rabbits were under ovariectomy. We compared plasma lipids, lipoproteins, and apolipoproteins of rabbits before and after surgery in each group fed either a chow diet or cholesterol-rich diet. Results On a chow diet, both male and female Tg rabbits showed lower plasma lipids than non-Tg counterparts and this lipid-lowering effect of EL was not affected by either orchiectomy in male or ovariectomy in female Tg rabbits. On a cholesterol diet; however, male Tg rabbits but not female Tg rabbits showed significant resistance to diet-induced hypercholesterolemia and atherosclerosis. The EL-mediated atheroprotective effect was eliminated after orchiectomy in male Tg rabbits. Female Tg rabbits showed similar levels of total cholesterol and lesion size of atherosclerosis compared with non-Tg rabbits and ovariectomy did not affect diet-induced hypercholesterolemia or atherosclerosis. Conclusion These results suggest that increased EL protects against diet-induced hypercholesterolemia and atherosclerosis. The beneficial effect of EL was dependent upon the presence of androgenic hormones.

Abstract 95: Naringenin Supplementation of a Low-Fat Diet Enhances the Reversal of Metabolic Dysfunction, Promotes Atherosclerosis Regression and Improves Lesion Pathology in Ldlr -/- Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Amy C Burke ◽  
Brian G Sutherland ◽  
Cynthia G Sawyez ◽  
Dawn E Telford ◽  
Murray W Huff
Keyword(s):  
Caloric Intake ◽  
Lesion Size ◽  
Chow Diet ◽  
Metabolic Dysfunction ◽  
Low Fat ◽  
Aortic Sinus ◽  
Rapid Weight Gain ◽  
Hepatic Expression ◽  
Low Fat Diet ◽  
Glucose Plasma

Diet-induced metabolic dysregulation (MetS) and atherosclerosis in mouse models can be reversed by intervention with a low-fat diet. Supplementation of a high-fat diet (HFHC) with naringenin prevents development of abnormal lipid and glucose metabolism and attenuates atherosclerosis. In the present study, we hypothesized that intervention by the addition of naringenin to a low-fat diet would enhance the reversal of MetS and atherosclerosis. Ldlr -/- mice were fed a HFHC diet for 12 weeks to induce MetS and intermediate atherosclerosis (baseline). Intervention for an additional 12 weeks consisted of transfer to: 1) a low-fat, isoflavone-free chow diet (IFF), 2) IFF with 3% naringenin (IFF+Nar) or 3) continuation on HFHC. HFHC-feeding induced rapid weight gain and adiposity, which were reversed to a greater extent by intervention with IFF+Nar (-93% and -76%, P <0.05) compared to IFF (-60% and -46%, P <0.05), independent of caloric intake. The hypercholesterolemia and hypertriglyceridemia induced by HFHC were further decreased by intervention with IFF+Nar (-105% and -124%, P <0.05) compared to IFF (-96% vs -103%, P <0.05). Hepatic lipids were normalized by both IFF+Nar and IFF, although IFF+Nar induced a greater decrease in liver triglyceride (-110% vs -86%, P =0.05). Hepatic expression of Pgc1a , Cpt1a and Pnpla2 were significantly higher with IFF+Nar compared to IFF. Fasting plasma glucose, plasma insulin and insulin sensitivity were further improved by IFF+Nar, compared to IFF. Relative to baseline, aortic cholesteryl ester (CE) increased with intervention by IFF alone (+40%), whereas IFF+Nar reversed aortic CE content (-19%, P <0.04). Compared to baseline, aortic sinus lesion size continued to increase with IFF (+47%), whereas with IFF+Nar lesion size increased only 14% ( P <0.05), indicating almost complete attenuation of lesion growth. Both intervention diets decreased lesion apoptotic cells similarly, although fewer lesion macrophages (35% vs 43%, P <0.05) and reduced necrotic area (6.5% vs 7.5%, trend) resulted from intervention with IFF+Nar, compared to IFF. In conclusion, intervention with naringenin enhances improvements in metabolic function, halts progression of atherosclerosis and improves lesion pathology.

scholarly journals Sex Differences in Lipid and Lipoprotein Metabolism: It's Not Just about Sex Hormones

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1192-1192
Author(s):  
Xuewen Wang ◽  
Faidon Magkos ◽  
Bettina Mittendorfer
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Plasma Lipids ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Men And Women ◽  
Beneficial Effects ◽  
Physiological Alterations ◽  
First Pass ◽  
Hormonal Milieu

Abstract It is commonly thought that sex hormones are important regulators of plasma lipid kinetics and are responsible for sexual dimorphism in the plasma lipid profile. Here we discuss the findings from studies evaluating lipid and lipoprotein kinetics in men and women in the context of what we know about the effects of exogenous sex hormone administration, and we conclude that it is more complicated than that. It has become clear that normal physiological alterations in the hormonal milieu (i.e. due to menopause or throughout the menstrual cycle) do not significantly affect plasma lipid homeostasis. Furthermore, parenterally administered estrogens have either no effect or only very small beneficial effects, whereas orally administered estrogens raise plasma triglyceride concentrations—a phenomenon that is not consistent with the observed sex differences and likely results from the hepatic “first-pass effect.” The effects of progestogens and androgens mimic only in part the differences in plasma lipids between men and women. Thus, the underlying physiological modulators of plasma lipid metabolism responsible for the differences between men and women remain to be elucidated.

scholarly journals Sex Differences in Lipid and Lipoprotein Metabolism: It's Not Just about Sex Hormones

2011 ◽  
Vol 96 (4) ◽  
pp. 885-893 ◽  
Author(s):  
Xuewen Wang ◽  
Faidon Magkos ◽  
Bettina Mittendorfer
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Plasma Lipids ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Men And Women ◽  
Beneficial Effects ◽  
Physiological Alterations ◽  
First Pass ◽  
Hormonal Milieu

Abstract It is commonly thought that sex hormones are important regulators of plasma lipid kinetics and are responsible for sexual dimorphism in the plasma lipid profile. Here we discuss the findings from studies evaluating lipid and lipoprotein kinetics in men and women in the context of what we know about the effects of exogenous sex hormone administration, and we conclude that it is more complicated than that. It has become clear that normal physiological alterations in the hormonal milieu (i.e. due to menopause or throughout the menstrual cycle) do not significantly affect plasma lipid homeostasis. Furthermore, parenterally administered estrogens have either no effect or only very small beneficial effects, whereas orally administered estrogens raise plasma triglyceride concentrations—a phenomenon that is not consistent with the observed sex differences and likely results from the hepatic “first-pass effect.” The effects of progestogens and androgens mimic only in part the differences in plasma lipids between men and women. Thus, the underlying physiological modulators of plasma lipid metabolism responsible for the differences between men and women remain to be elucidated.

Abstract 650: Ceramide as a Mediator of Insulin Resistance--Associated Atherosclerosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Takhar Kasumov ◽  
Ling Li ◽  
Stephen Previs ◽  
Kailash Gulshan ◽  
Belinda Willard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Plasma Lipids ◽  
De Novo ◽  
Lipoprotein Metabolism ◽  
Western Diet ◽  
Sphingolipid Metabolism ◽  
Chow Diet ◽  
Turnover Rates ◽  
Serum Triglycerides ◽  
Long Chain

Objectives: Insulin resistance-induced hyperlipidemia and hyperlipoproteinemia are risk factors of atherosclerosis. Spingolipid ceramide is involved in insulin resistance and lipoprotein metabolism, and sphingomyelin, a ceramide metabolite, is an independent risk factor for CVD. Here we studied the role of spingolipids in insulin resistance associated atherosclerosis. Methods: Low density lipoprotein receptors knockout (LDLR -/- ) mice, a diet induced mouse model of insulin resistance and atherosclerosis, were fed a standard chow diet or a western diet (high fat with 0.2% cholesterol) for 12 weeks with or without myriocin, an inhibitor of de novo ceramide synthesis. A targeted lipidomics approach was used for hepatic and plasma profiling of ceramides. Metabolic 2 H 2 O-labeling technique was applied to quantify turnover rates of hepatic and plasma lipids and lipoproteins, including ApoB and ApoAI - the principle proteins of VLDL/LDL and HDL. Hepatic and intestinal expression of genes and proteins involved in insulin signaling, lipid and lipoprotein metabolism were characterized. Results: A western diet caused insulin resistance, increased hepatic and serum triglycerides and the altered distribution of hepatic ceramides, i.e. hepatic levels of long chain ceramides (C16 & C18), involved in apoptosis, were increased by 80% and 27%, respectively, while a very-long chain ceramide C24 was reduced more than twice. A western diet also induced dyslipidemia, hepatic oxidative stress, inflammation, apoptosis, mild fibrosis, and atherosclerosis. The plasma ratio of ApoB/ApoA1 was increased >2 fold which was due to increased production of ApoB. HDL turnover was not affected. Pharmacologic inhibition of sphingolipid biosynthesis with myriocin improved insulin sensitivity, hepatic steatosis, fibrosis, apoptosis, and prevented atherosclerosis. These changes were associated with decreased lipogenesis and ApoB production. In addition, myriocin significantly increased both plasma levels and flux of HDL. Conclusions: Modulation of sphingolipid metabolism may lead to the development of novel therapeutic strategies for the treatment of insulin resistance and associated atherosclerosis.

The Effect of n-3 Fatty Acids on Lipids and Haemostasis in Patients with Type lla and Type IV Hyperlipidaemia

1989 ◽  
Vol 62 (02) ◽  
pp. 797-801 ◽  
Author(s):  
E Berg Schmidt ◽  
E Ernst ◽  
K Varming ◽  
J O Pedersen ◽  
J Dyerberg
Keyword(s):  
Fatty Acids ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Apolipoprotein A1 ◽  
Type Iv ◽  
Before And After ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryPlasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type II a and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.

scholarly journals From evidence to practice: development of web-based Dutch lipid reference values

2021 ◽  
Author(s):  
N. S. Nurmohamed ◽  
D. Collard ◽  
J. W. Balder ◽  
J. A. Kuivenhoven ◽  
E. S. G. Stroes ◽  
...  
Keyword(s):  
The Netherlands ◽  
Reference Values ◽  
Plasma Lipids ◽  
Digital Health ◽  
Reference Value ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Cascading Style Sheets ◽  
Age And Sex

Abstract Introduction In the Netherlands, the total number of yearly measured lipid profiles exceeds 500,000. While lipid values are strongly affected by age and sex, until recently, no up-to-date age- and sex-specific lipid reference values were available. We describe the translation of big-cohort lipid data into accessible reference values, which can be easily incorporated in daily clinical practice. Methods Lipid values (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) from all healthy adults and children in the LifeLines cohort were used to generate age- and sex-specific percentiles. A combination of RStudio, Cascading Style Sheets and HyperText Markup Language was used to interactively display the percentiles in a responsive web layout. Results After exclusion of subjects reporting cardiovascular disease or lipid-lowering therapy at baseline, 141,611 subjects were included. On the website, input fields were created for age, sex and all main plasma lipids. Upon input of these values, corresponding percentiles are calculated, and output is displayed in a table and an interactive graph for each lipid. The website has been made available in both Dutch and English and can be accessed at www.lipidtools.com. Conclusion We constructed the first searchable, national lipid reference value tool with graphical display in the Netherlands to use in screening for dyslipidaemias and to reduce the underuse of lipid-lowering therapy in Dutch primary prevention. This study illustrates that data collected in big-cohort studies can be made easily accessible with modern digital techniques and preludes the digital health revolution yet to come.

Preoperative and postoperative cognitive functioning in patients with frontal meningiomas

2003 ◽  
Vol 98 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Oliver Tucha ◽  
Christian Smely ◽  
Michael Preier ◽  
Georg Becker ◽  
Geraldine M. Paul ◽  
...  
Keyword(s):  
Executive Functions ◽  
Cognitive Functioning ◽  
Time Course ◽  
Lesion Size ◽  
Test Battery ◽  
Surgical Removal ◽  
Specific Information ◽  
Content Type ◽  
Before And After ◽  
Fine Print

Object. There is presently no specific information available concerning the nature and course of cognitive deficits caused by intracranial meningiomas. In this prospective study the authors examined the cognitive functioning of patients with frontal meningiomas. Methods. Fifty-four patients with frontal meningiomas were examined neuropsychologically before and after neurosurgery. The test battery consisted of standardized instruments including those assessing memory, attention, visuoconstructive abilities, and executive functions. The time period between pre-and postoperative assessment ranged from 4 to 9 months. The patients' performance was compared with the results in 54 healthy adults who were also assessed twice by using the same test battery in a period ranging from 4 to 9 months. In addition, the effect on cognition of meningioma lateralization, localization, lesion size, edema, brain compression, time course, and the occurrence of preoperative seizures was analyzed. Conclusions. Except in the case of working memory, comparisons of pre- and postoperative assessments of cognition revealed no differences in memory, visuoconstructive abilities, or executive functions, although a postoperative improvement in attentional functions was observed. The results of this study indicate that the surgical removal of frontal meningiomas does not impair patients' cognitive functioning. Furthermore, improvements in attentional functions may occur in these patients.

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