Cholesteryl ester transfer protein: ace of spades, queen of hearts, or the joker?

Miller, N. E.

doi:10.3389/fphar.2015.00145

Cited by 5 publications

(5 citation statements)

References 24 publications

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“…One plausible mechanism linking carbohydrate restriction and weight loss to improved HDL metabolism is via cholesteryl ester transfer protein (CETP). The activity of this enzyme, which transfers cholesteryl ester from HDL particles to LDL and VLDL particles in exchange for triglyceride, is known to be significantly increased in CVD and obesity and normalize in parallel with weight loss (Miller, 2015[ 25 ]; Scharnagl et al, 2014[ 36 ]). It is plausible that excess dietary intake of refined carbohydrates upregulates CETP activity, perhaps via postprandial and/or chronic elevations of glucose, insulin, triglyceride, and/or VLDL (Kontush et al, 2013[ 18 ]; Miller, 2015[ 25 ]; Scharnagl et al, 2014[ 36 ]; Sprandel et al 2015[ 41 ]), and carbohydrate restriction plausibly reverses this hyperactivity, especially in the setting of insulin re-sistance and atherogenic dyslipidaemia.…”

Section: Discussionmentioning

confidence: 99%

“…The activity of this enzyme, which transfers cholesteryl ester from HDL particles to LDL and VLDL particles in exchange for triglyceride, is known to be significantly increased in CVD and obesity and normalize in parallel with weight loss (Miller, 2015[ 25 ]; Scharnagl et al, 2014[ 36 ]). It is plausible that excess dietary intake of refined carbohydrates upregulates CETP activity, perhaps via postprandial and/or chronic elevations of glucose, insulin, triglyceride, and/or VLDL (Kontush et al, 2013[ 18 ]; Miller, 2015[ 25 ]; Scharnagl et al, 2014[ 36 ]; Sprandel et al 2015[ 41 ]), and carbohydrate restriction plausibly reverses this hyperactivity, especially in the setting of insulin re-sistance and atherogenic dyslipidaemia. This hypothesized mechanism is compatible with other data showing that carbohydrate restriction and weight loss each improve levels of small dense LDL particles (Siri-Tarino et al, 2009[ 40 ]; Tay et al 2014[ 45 ]; Volek et al, 2009[ 48 ]), and the strong correlation between improvements in large HDL and small-dense LDL particles is consistent with a common underlying mechanism (Mascarenhas-Melo et al, 2013[ 23 ]; Shoji et al, 2009[ 39 ]).…”

Section: Discussionmentioning

confidence: 99%

“…Measuring large HDL levels via 2-dimensional electrophoresis is a highly accurate method for measuring large HDL particle levels (Dullens et al, 2007[ 6 ]; Rosenson et al, 2013[ 29 ]; Warnick, 2000[ 49 ]), however many clinicians are unfamiliar with the use of this technology in the clinical setting. Furthermore, although large HDL particles are more strongly predictive of cardiovascular disease prevention than HDL cholesterol levels, our study did not measure levels of HDL functionality, CETP activity, or lecithin-cholesterol acyltransferase (LCAT) activity, which may have added important insights (Kontush et al, 2013[ 18 ]; Miller, 2015[ 25 ]; Scharnagl et al, 2014[ 36 ]; Sprandel et al 2015[ 41 ]).…”

Section: Discussionmentioning

confidence: 99%

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The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss

Finelli,

Crispino,

Gioia

et al. 2016

EXCLI Journal; 15:Doc166; ISSN 1611-2156

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss

Finelli,

Crispino,

Gioia

et al. 2016

EXCLI Journal; 15:Doc166; ISSN 1611-2156

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“…There may be several reasons for this. First, CETP inhibition per se may not be antiatherogenic (88). It has been increasingly suggested that HDL function instead of concentration may underlie its link to CVD benefits (26).…”

Section: Cholesteryl Ester Transfer Protein Inhibitorsmentioning

confidence: 99%

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol

et al. 2016

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Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives in Diabetes article, we emphasize that changing demographics and lifestyles over the past few decades have resulted in an epidemic of the "atherogenic dyslipidemia complex," the main features of which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes in LDL particles, accumulation of remnant lipoproteins, and postprandial hyperlipidemia. We briefly review the underlying pathophysiology of this form of dyslipidemia, in particular its association with insulin resistance, obesity, and type 2 diabetes, and the marked atherogenicity of this condition. We explain the failure of existing classes of therapeutic agents such as fibrates, niacin, and cholesteryl ester transfer protein inhibitors that are known to modify components of the atherogenic dyslipidemia complex. Finally, we discuss targeted repurposing of existing therapies and review promising new therapeutic strategies to modify the atherogenic dyslipidemia complex. We postulate that targeting the central abnormality of the atherogenic dyslipidemia complex, the elevation of triglyceriderich lipoprotein particles, represents a new frontier in CVD prevention and is likely to prove the most effective strategy in correcting most aspects of the atherogenic dyslipidemia complex, thereby preventing CVD events.

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“…The underlying mechanism by which CETP transfers lipoprotein is still not clearly understood, and the fundamental function of CETP in nature remains unknown [ 9 , 33 ]. The PLS-DA model not only distinguished the metabolic components of genetically modified pigs from unmodified pigs, but also showed discrepancy between transgenic positive and cloned pigs.…”

Section: Discussionmentioning

confidence: 99%

A novel swine model for evaluation of dyslipidemia and atherosclerosis induced by human CETP overexpression

et al. 2017

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BackgroundThe mechanism of cholesteryl ester transfer protein (CETP) in lipid metabolism is still unclear. Furthermore, the relationship of CETP and atherosclerosis (AS) has been controversial. As pigs are a good model for both lipid and AS research, we investigated the lipid metabolism of human CETP (hCETP) transgenic pigs and explored the mechanism of CETP in lipid modulation.MethodsPlasmids expressing the hCETP gene were designed, successfully constructed, and transfected into porcine fetal fibroblasts by liposomes. Using somatic cell nuclear transfer technology and embryonic transfer, hCETP transgenic pigs were generated. After the DNA, RNA, and protein levels were identified, positive hCETP transgenic pigs were selected. Blood samples were collected at different ages to evaluate the phenotypes of biochemical markers, and the metabolomes of plasma samples were analyzed by liquid mass spectrometry.ResultsEight positive hCETP transgenic pigs and five negative cloned pigs were generated by transgenic technology. Finally, five hCETP transgenic and five cloned pigs were grown healthily. After feeding with a normal diet, hCETP transgenic pigs compared with unmodified pigs had no significant differences in body weight, liver function, kidney function, or plasma ions, while total cholesterol and low-density lipoprotein were higher than in unmodified pigs, and high-density lipoprotein was significantly decreased. Metabolomics analysis showed that there were differences in metabolic components between hCETP transgenic pigs, cloned pigs, and unmodified pigs.ConclusionsIn this study, we created hCETP transgenic pigs that could serve as an excellent model for lipid disorders and atherosclerosis.Electronic supplementary materialThe online version of this article (10.1186/s12944-017-0563-x) contains supplementary material, which is available to authorized users.

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Cholesteryl ester transfer protein: ace of spades, queen of hearts, or the joker?

Cited by 5 publications

References 24 publications

The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss

The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol

A novel swine model for evaluation of dyslipidemia and atherosclerosis induced by human CETP overexpression

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