scholarly journals Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function

2020 ◽  
Vol 21 (23) ◽  
pp. 8985
Author(s):  
Julia T. Stadler ◽  
Gunther Marsche
Keyword(s):  
High Density Lipoprotein ◽  
Virgin Olive Oil ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Hdl Function ◽  
Increased Risk ◽  
And Function ◽  
The Impact

In obese individuals, atherogenic dyslipidemia is a very common and important factor in the increased risk of cardiovascular disease. Adiposity-associated dyslipidemia is characterized by low high-density lipoprotein cholesterol (HDL-C) levels and an increase in triglyceride-rich lipoproteins. Several factors and mechanisms are involved in lowering HDL-C levels in the obese state and HDL quantity and quality is closely related to adiponectin levels and the bioactive lipid sphingosine-1-phosphate. Recent studies have shown that obesity profoundly alters HDL metabolism, resulting in altered HDL subclass distribution, composition, and function. Importantly, weight loss through gastric bypass surgery and Mediterranean diet, especially when enriched with virgin olive oil, is associated with increased HDL-C levels and significantly improved metrics of HDL function. A thorough understanding of the underlying mechanisms is crucial for a better understanding of the impact of obesity on lipoprotein metabolism and for the development of appropriate therapeutic approaches. The objective of this review article was to summarize the newly identified changes in the metabolism, composition, and function of HDL in obesity and to discuss possible pathophysiological consequences.

scholarly journals HDL in the 21st Century: A Multifunctional Roadmap for Future HDL Research

Circulation ◽  
2021 ◽  
Vol 143 (23) ◽  
pp. 2293-2309
Author(s):  
Anand Rohatgi ◽  
Marit Westerterp ◽  
Arnold von Eckardstein ◽  
Alan Remaley ◽  
Kerry-Anne Rye
Keyword(s):  
Cardiovascular Risk ◽  
High Density Lipoprotein ◽  
Therapeutic Target ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Optimal Time ◽  
Bioactive Lipids ◽  
Hdl Function ◽  
Increased Risk

Low high-density lipoprotein cholesterol (HDL-C) characterizes an atherogenic dyslipidemia that reflects adverse lifestyle choices, impaired metabolism, and increased cardiovascular risk. Low HDL-C is also associated with increased risk of inflammatory disorders, malignancy, diabetes, and other diseases. This epidemiologic evidence has not translated to raising HDL-C as a viable therapeutic target, partly because HDL-C does not reflect high-density lipoprotein (HDL) function. Mendelian randomization analyses that have found no evidence of a causal relationship between HDL-C levels and cardiovascular risk have decreased interest in increasing HDL-C levels as a therapeutic target. HDLs comprise distinct subpopulations of particles of varying size, charge, and composition that have several dynamic and context-dependent functions, especially with respect to acute and chronic inflammatory states. These functions include reverse cholesterol transport, inhibition of inflammation and oxidation, and antidiabetic properties. HDLs can be anti-inflammatory (which may protect against atherosclerosis and diabetes) and proinflammatory (which may help clear pathogens in sepsis). The molecular regulation of HDLs is complex, as evidenced by their association with multiple proteins, as well as bioactive lipids and noncoding RNAs. Clinical investigations of HDL biomarkers (HDL-C, HDL particle number, and apolipoprotein A through I) have revealed nonlinear relationships with cardiovascular outcomes, differential relationships by sex and ethnicity, and differential patterns with coronary versus noncoronary events. Novel HDL markers may also have relevance for heart failure, cancer, and diabetes. HDL function markers (namely, cholesterol efflux capacity) are associated with coronary disease, but they remain research tools. Therapeutics that manipulate aspects of HDL metabolism remain the holy grail. None has proven to be successful, but most have targeted HDL-C, not metrics of HDL function. Future therapeutic strategies should focus on optimizing HDL function in the right patients at the optimal time in their disease course. We provide a framework to help the research and clinical communities, as well as funding agencies and stakeholders, obtain insights into current thinking on these topics, and what we predict will be an exciting future for research and development on HDLs.

Gene Therapy to Improve High-Density Lipoprotein Metabolism and Function

2010 ◽  
Vol 16 (13) ◽  
pp. 1531-1544 ◽  
Author(s):  
Eline Van Craeyveld ◽  
Stephanie Gordts ◽  
Frank Jacobs ◽  
Bart De Geest
Keyword(s):  
Gene Therapy ◽  
High Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
High Density ◽  
And Function

scholarly journals The impact of aerobic and isometric exercise on different measures of dysfunctional high-density lipoprotein in patients with hypertension

2019 ◽  
Vol 26 (12) ◽  
pp. 1301-1309 ◽  
Author(s):  
Nikolaos Pagonas ◽  
Stergios Vlatsas ◽  
Frederic Bauer ◽  
Felix S Seibert ◽  
B Sasko ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
High Density Lipoprotein ◽  
Aerobic Exercise ◽  
Isometric Exercise ◽  
Density Lipoprotein ◽  
High Density ◽  
Hdl Function ◽  
Antioxidant Function ◽  
The Impact

Background Exercise training increases high-density lipoprotein (HDL) cholesterol, but its effect on HDL function is unclear. In hypertensives, exercise improves endothelial dysfunction, which is related to HDL function. In the present study, we assess for the first time the effects of different exercise modalities on two cell-free assays of HDL function. Design The study was conducted as a prospective randomized controlled trial in 75 hypertensive patients. Methods Patients were randomized in three groups: (a) handgrip isometric training five times weekly; (b) placebo-handgrip; and (c) aerobic exercise training at least three times per week. HDL function was assessed in serum samples at baseline and after 12 weeks of training by two independent assays that determine the proinflammatory phenotype (haptoglobin content) of a specific amount of HDL (Haptoglobin-HDL [HPHDL]) and oxidized HDL (HDLox) as a measure of reduced antioxidant function of HDL. HDL function measures were normalized by the measures of a pooled control of sera from healthy participants and by HDL-C levels (normalized ratio, no units). Results Aerobic exercise led to significant reduction of the HDLox from 0.99 ± 0.27 to 0.90 ± 0.29 (no units, p = 0.03). The HPHDL did not change in any training group. Changes of HDLox correlated with reduction of the systolic blood pressure only after aerobic exercise ( R = 0.64, p = 0.03). Conclusions Aerobic but not isometric exercise improves the antioxidant function of HDL in patients with hypertension. This improvement correlates positively with reductions of blood pressure.

Abstract 407: Atherogenic Dyslipidemia in Patients with Diabetes Mellitus May Have Distinct High Density Lipoprotein Function

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Wenliang Song ◽  
Jing Du ◽  
Li Qin ◽  
Stuart Zarich ◽  
Sachin Majumdar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Platelet Aggregation ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Profiles ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Platelet Apoptosis ◽  
Hdl Function ◽  
Two Populations

There is growing evidence suggesting that high-density lipoprotein (HDL) function is more important than the HDL cholesterol (HDL-C) levels. HDL particles are highly heterogeneous and their function may also differ among different patient populations. There are two populations that are recognized tohave significant residual cardiovascular risk despite intensive statin therapy: atherogenic dyslipidaemia and diabetes mellitus. Atherogenic dyslipidemia and diabetes have significant homology with regards to lipid profiles. However, systemic epidemiological studies that describes the overlapping profiles between atherogenic dyslipidemia and diabetes is lacking. The function and types of HDL in these two populations needs to be carefully elucidated. HDL has many functions includingreverse cholesterol transport, anti-oxidant activity and anti-inflammatory activity. HDL may also exert “antiplatelet effects”but the mechanism is unclear.We assessed the prevalence of atherogenic dyslipidemia in diabetes mellitus using data from the National Health and Nutrition Examination Survery (NHANES) and data from Yale New Haven Health (YNHH). We found that atherogenic dyslipidemia and diabetes mellitushave overlapping lipid profiles but are clearly two distinct conditions. In our preliminary studies, we found that HDL inhibits platelet aggregation and activation. Very interestingly, we found HDL can induce mitochondria dependent platelet apoptosis. The antiplatelet effect of HDL, as observed by others in the past, may arise fromapoptotic platelets that do not aggregate, and thus the inhibition of platelet aggregation. Whether HDL subtypes from atherogenic dyslipidemia and diabetes patient have differential effects on platelet apoptosis are currently being investigated.

scholarly journals HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition

2020 ◽  
Author(s):  
Samar R. El Khoudary ◽  
Xirun Chen ◽  
Alexis Nasr ◽  
Jeff Billheimer ◽  
Maria Mori Brooks ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Lipid Content ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Menstrual Period ◽  
Resonance Spectroscopy ◽  
Hdl Function ◽  
Menopause Transition ◽  
And Function

Objective: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. Conclusions: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

scholarly journals Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

2001 ◽  
Vol 42 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Sylvie Braschi ◽  
Cynthia R. Coffill ◽  
Tracey A-M. Neville ◽  
Darren M. Hutt ◽  
Daniel L. Sparks
Keyword(s):  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Structure And Function ◽  
High Density ◽  
Lipoprotein Particles ◽  
And Function

scholarly journals Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism

2015 ◽  
Vol 291 (6) ◽  
pp. 2799-2811 ◽  
Author(s):  
Ruwanthi N. Gunawardane ◽  
Preston Fordstrom ◽  
Derek E. Piper ◽  
Stephanie Masterman ◽  
Sophia Siu ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Acyltransferase ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
High Density ◽  
Human Antibodies ◽  
Lecithin Cholesterol Acyltransferase
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