Application of Fluorescence Correlation Spectroscopy to Measure High-Density Lipoprotein (HDL) Metabolism

abstract To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL[ namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.

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Insulin-Like Growth Factor Type I (Somatomedin-C) Stimulates High Density Lipoprotein (HDL) Metabolism and HDL-Supported Progesterone Biosynthesis by Swine Granulosa Cellsin Vitro*

Endocrinology ◽

10.1210/endo-124-6-3069 ◽

1989 ◽

Vol 124 (6) ◽

pp. 3069-3076 ◽

Cited By ~ 9

Author(s):

JOHANNES D. VELDHUIS ◽

JOHN T. GWYNNE

Keyword(s):

Growth Factor ◽

High Density Lipoprotein ◽

Density Lipoprotein ◽

High Density ◽

Type I ◽

Insulin Like Growth Factor ◽

Somatomedin C ◽

Factor Type ◽

Hdl Metabolism ◽

Progesterone Biosynthesis

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A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.94.23.12610 ◽

1997 ◽

Vol 94 (23) ◽

pp. 12610-12615 ◽

Cited By ~ 628

Author(s):

A. Rigotti ◽

B. L. Trigatti ◽

M. Penman ◽

H. Rayburn ◽

J. Herz ◽

...

Keyword(s):

High Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

High Density ◽

Type I ◽

Gene Encoding ◽

Scavenger Receptor Class ◽

Targeted Mutation ◽

Class B ◽

Hdl Metabolism

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High-density lipoprotein (HDL) metabolism and bone mass

Journal of Endocrinology ◽

10.1530/joe-16-0657 ◽

2017 ◽

Vol 233 (2) ◽

pp. R95-R107 ◽

Cited By ~ 12

Author(s):

Nicholaos I Papachristou ◽

Harry C Blair ◽

Kyriakos E Kypreos ◽

Dionysios J Papachristou

Keyword(s):

Bone Mass ◽

High Density Lipoprotein ◽

Current Knowledge ◽

Density Lipoprotein ◽

Osteoblastic Differentiation ◽

High Density ◽

Inflammatory Microenvironment ◽

Marrow Adiposity ◽

And Function ◽

Hdl Metabolism

It is well appreciated that high-density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models, have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in metabolic pathways of HDL favors adipoblastic differentiation and restrains osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades. Increased bone marrow adiposity also deteriorates bone osteoblastic function and thus bone synthesis, leading to reduced bone mass. In this review, we present the current knowledge and the future directions with regard to the HDL–bone mass connection. Unraveling the molecular phenomena that underline this connection will promote the deeper understanding of the pathophysiology of bone-related pathologies, such as osteoporosis or bone metastasis, and pave the way toward the development of novel and more effective therapies against these conditions.

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High Density Lipoprotein (HDL) Metabolism in Noninsulin-Dependent Diabetes Mellitus: Measurement of HDL Turnover Using Tritiated HDL*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-65-3-512 ◽

1987 ◽

Vol 65 (3) ◽

pp. 512-518 ◽

Cited By ~ 102

Author(s):

A. GOLAY ◽

L. ZECH ◽

M.-Z. SHI ◽

Y.-A. M. CHIOU ◽

G. M. REAVEN ◽

...

Keyword(s):

Diabetes Mellitus ◽

High Density Lipoprotein ◽

Density Lipoprotein ◽

High Density ◽

Dependent Diabetes Mellitus ◽

Hdl Metabolism

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Lipoprotein distribution and serum concentrations of 7α-hydroxy-4-cholesten-3-one and bile acids: effects of monogenic disturbances in high-density lipoprotein metabolism

Clinical Science ◽

10.1042/cs20110482 ◽

2011 ◽

Vol 122 (8) ◽

pp. 385-400 ◽

Cited By ~ 4

Author(s):

Carine Steiner ◽

Adriaan G. Holleboom ◽

Ratna Karuna ◽

Mohammad M. Motazacker ◽

Jan Albert Kuivenhoven ◽

...

Keyword(s):

High Density Lipoprotein ◽

Hepatic Lipase ◽

Plasma Concentrations ◽

Density Lipoprotein ◽

High Density ◽

Low Density ◽

Serum Concentrations ◽

Very Low Density Lipoproteins ◽

Hdl Metabolism ◽

Lipoprotein Distribution

BA (bile acid) formation is considered an important final step in RCT (reverse cholesterol transport). HDL (high-density lipoprotein) has been reported to transport BAs. We therefore investigated the effects of monogenic disturbances in human HDL metabolism on serum concentrations and lipoprotein distributions of the major 15 BA species and their precursor C4 (7α-hydroxy-4-cholesten-3-one). In normolipidaemic plasma, approximately 84%, 11% and 5% of BAs were recovered in the LPDS (lipoprotein-depleted serum), HDL and the combined LDL (low-density lipoprotein)/VLDL (very-low-density lipoproteins) fraction respectively. Conjugated BAs were slightly over-represented in HDL. For C4, the respective percentages were 23%, 21% and 56% (41% in LDL and 15% in VLDL) respectively. Compared with unaffected family members, neither HDL-C (HDL-cholesterol)-decreasing mutations in the genes APOA1 [encoding ApoA-I (apolipoprotein A-I], ABCA1 (ATP-binding cassette transporter A1) or LCAT (lecithin:cholesterol acyltransferase) nor HDL-C-increasing mutations in the genes CETP (cholesteryl ester transfer protein) or LIPC (hepatic lipase) were associated with significantly different serum concentrations of BA and C4. Plasma concentrations of conjugated and secondary BAs differed between heterozygous carriers of SCARB1 (scavenger receptor class B1) mutations and unaffected individuals (P<0.05), but this difference was not significant after correction for multiple testing. Moreover, no differences in the lipoprotein distribution of BAs in the LPDS and HDL fractions from SCARB1 heterozygotes were observed. In conclusion, despite significant recoveries of BAs and C4 in HDL and despite the metabolic relationships between RCT and BA formation, monogenic disorders of HDL metabolism do not lead to altered serum concentrations of BAs and C4.

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High-density lipoprotein metabolism in human apolipoprotein B100transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia

Applied Physiology Nutrition and Metabolism ◽

10.1139/h11-003 ◽

2011 ◽

Vol 36 (3) ◽

pp. 313-322 ◽

Cited By ~ 4

Author(s):

Sarah J. Ehlers ◽

Stephanie M. Larson ◽

Heather E. Rasmussen ◽

Young-Ki Park ◽

Ji-Young Lee

Keyword(s):

Adipose Tissue ◽

High Density Lipoprotein ◽

Brown Adipose Tissue ◽

Density Lipoprotein ◽

High Density ◽

Type I ◽

Human Apolipoprotein ◽

Protein Levels ◽

Brown Adipose ◽

Hdl Metabolism

Obese and diabetic humans display decreased plasma high-density lipoprotein cholesterol (HDL-C) concentrations and an increased risk for coronary heart disease. However, investigation on HDL metabolism in obesity with a particular emphasis on hepatic ATP-binding cassette transporter A1 (ABCA1), the primary factor for HDL formation, has not been well studied. Human apolipoprotein B100transgenic (hApoBtg) and brown adipose tissue deficient (BATless) mice were crossed to generate hApoBtg/BATless mice. Male and female hApoBtgand hApoBtg/BATless mice were maintained on either a regular rodent chow diet or a diet high in fat and cholesterol until 24 weeks of age. The hApoBtg/BATless mice that were fed a HF/HC diet became obese, developed hepatic steatosis, and had significantly elevated plasma insulin levels compared with their hApoBtgcounterparts, but plasma concentrations of total cholesterol, HDL-C, triglycerides, and free fatty acids and lipoprotein distribution between genotypes were not significantly different. Hepatic expression of genes encoding HDL-modifying factors (e.g., scavenger receptor, class B, type I, hepatic lipase, lecithin:cholesterol acyltransferase, and phospholipid transfer protein) was either altered significantly or showed a trend of difference between 2 genotypes of mice. Importantly, hepatic protein levels of ABCA1 were significantly lowered by ∼35% in male obese hApoBtg/BATless mice with no difference in mRNA levels compared with hApoBtgcounterparts. Despite reduced hepatic ABCA1 protein levels, plasma HDL-C concentrations were not altered in male obese hApoBtg/BATless mice. The result suggests that hepatic ABCA1 may not be a primary contributing factor for perturbations in HDL metabolism in obesity-induced hyperinsulinemia.

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Structural and Functional Impairments of Reconstituted High-Density Lipoprotein by Incorporation of Recombinant β-Amyloid42

Molecules ◽

10.3390/molecules26144317 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4317

Author(s):

Kyung-Hyun Cho

Keyword(s):

High Density Lipoprotein ◽

Bound States ◽

Density Lipoprotein ◽

High Density ◽

Molar Ratio ◽

Dependent Manner ◽

Functional Impairments ◽

Amyloid Aβ ◽

Co Addition ◽

Hdl Metabolism

Beta (β)-amyloid (Aβ) is a causative protein of Alzheimer’s disease (AD). In the pathogenesis of AD, the apolipoprotein (apo) A-I and high-density lipoprotein (HDL) metabolism is essential for the clearance of Aβ. In this study, recombinant Aβ42 was expressed and purified via the pET-30a expression vector and E.coli production system to elucidate the physiological effects of Aβ on HDL metabolism. The recombinant human Aβ protein (51 aa) was purified to at least 95% purity and characterized in either the lipid-free and lipid-bound states with apoA-I. Aβ was incorporated into the reconstituted HDL (rHDL) (molar ratio 95:5:1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol:apoA-I) with various apoA-I:Aβ ratios from 1:0 to 1:0.5, 1:1 and 1:2. With an increasing molar ratio of Aβ, the α-helicity of apoA-I was decreased from 62% to 36% with a red shift of the Trp wavelength maximum fluorescence from 337 to 340 nm in apoA-I. The glycation reaction of apoA-I was accelerated further by the addition of Aβ. The treatment of fructose and Aβ caused more multimerization of apoA-I in the lipid-free state and in HDL. The phospholipid-binding ability of apoA-I was impaired severely by the addition of Aβ in a dose-dependent manner. The phagocytosis of LDL into macrophages was accelerated more by the presence of Aβ with the production of more oxidized species. Aβ severely impaired tissue regeneration, and a microinjection of Aβ enhanced embryotoxicity. In conclusion, the beneficial functions of apoA-I and HDL were severely impaired by the addition of Aβ via its detrimental effect on secondary structure. The impairment of HDL functionality occurred more synergistically by means of the co-addition of fructose and Aβ.

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