Cholesteryl ester transfer protein promotes the formation of cholesterol-rich remnant like lipoprotein particles in human plasma

Okamoto, Hiroshi; Miyai, Atsuko; Sasase, Tomohiko; Furukawa, Noboru; Matsushita, Mutsuyoshi; Nakano, Takamitsu; Nakajima, Katsuyuki

doi:10.1016/j.cca.2006.06.015

Cited by 19 publications

(11 citation statements)

References 34 publications

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“…These results indicate that formation of RLP-C is controlled by a different metabolic pathway from that of RLP-TG. RLP-C formation is known to be strongly associated with cholesteryl ester transfer protein activity in plasma, [34][35][36] while RLP-TG formation is known to be associated with LPL activity which is partly activated by adiponectin. [37][38][39][40] RLP-TG was most strongly associated with waist circumference among the variables studied, indicating a specific marker of MetS by factor analysis ( Table 6).…”

Section: Discussionmentioning

confidence: 99%

Plasma adiponectin is a more specific marker of fatty liver than a marker of metabolic syndrome in Japanese men

et al. 2013

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Background: The association of plasma cardiovascular risk markers and metabolic syndrome (MetS) with non-alcoholic fatty liver disease (NAFLD) has not been well defined. Methods: Japanese men (n ¼ 809) had standard anthropometric measurements done, and had their liver fat quantitated by ultrasound. Three groups were identified: (1) normal controls without significant disease, (2) preliminary-metabolic syndrome (pre-MetS) cases and (3) MetS cases. Plasma adiponectin, high sensitivity-C reactive protein (hs-CRP), HOMA-IR, lipids, lipoproteins and liver enzymes were evaluated among the three groups. Results: The prevalence of fatty liver was 13% in controls, 39% in pre-MetS and 62% in MetS. Plasma adiponectin and high density lipoprotein cholesterol (HDL-C) were significantly decreased, and HOMA-IR, hs-CRP, TG, remnant lipoproteins (RLPs) and small dense-LDL-C (sd LDL-C) were significantly increased in subjects with fatty liver compared to those without fatty liver. Multivariate analyses of serum parameters associated with fatty liver revealed that adiponectin and hs-CRP were more strongly associated with the presence of fatty liver than waist circumference. However, HOMA-IR, HDL-C, TG, RLP-C, RLP-TG and sd LDL-C were more strongly associated with waist circumference than with fatty liver. Factor analysis revealed that adiponectin and HDL-C were linked to liver enzymes, lipoproteins and HOMA-IR associated with fatty liver, but not with waist circumference. Conclusions: Adiponectin was found to be a more specific diagnostic marker for the presence of fatty liver regardless of MetS status, and was inversely correlated with liver enzyme concentrations. However, RLPs were found to be more specifically associated with the presence of MetS.

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Section: Discussionmentioning

confidence: 99%

Plasma adiponectin is a more specific marker of fatty liver than a marker of metabolic syndrome in Japanese men

et al. 2013

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“…However, in this case subject, the serum RLP-C level was highly elevated in fasting and did not increase after a fat load but rather decreased, while the RLP-TG and total TG levels significantly increased after a fat load with a delayed peak time compared with those of normal control subjects. This phenomenon indicated that CETP and HDL played an important role for the formation of RLP-C, as previously reported on postprandial lipid metabolism in homo-and heterozygous CETP deficiency cases 24 and as reported on an in vitro study by Okamoto et al 29 However, interestingly, RLP-TG and total TG levels in the case subject increased significantly at 240 mins after a fat load like those in common hyperlipidaemic patients. The trend of the case subject was similar to that of individuals treated with estrogen whose serum RLP-C level is reduced but RLP-TG level increases after the treatment.…”

Section: Discussionmentioning

confidence: 50%

“…Because of CETP deficiency, his HDL cannot exchange its cholesteryl ester with the TG of other lipoprotein particles, including RLP. 24,29 In this case, it is not easy to assume that CETP deficiency originated the cause of this unique profile of postprandial RLP-C and RLP-TG. A similar CETP deficient case with abnormally elevated TG was previously reported by Ritsch et al 30 and precise genetic analysis of CETP was performed to find the cause of the dissociation between cholesteryl ester and TG transportation in plasma.…”

Section: Discussionmentioning

confidence: 99%

A deficiency of cholesteryl ester transfer protein whose serum remnant-like particle-triglyceride significantly increased, but serum remnant-like particle-cholesterol did not after an oral fat load

Tanaka

Shimokado

et al. 2009

Ann Clin Biochem

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Background: We found a unique cholesteryl ester transfer protein (CETP) deficient case with markedly elevated serum triglyceride (TG) as well as high-density lipoprotein cholesterol (HDL-C) levels. Most of the CETP deficiency cases were reported to have normal or reduced serum TG with elevated HDL-C. Methods: The case subject was a 40-year-old male with a compound heterozygous CETP deficiency. Two heterozygous CETP deficient cases and 10 normal volunteers were also recruited as controls. They underwent an oral fat tolerance test (OFTT) and their blood was taken at fasting and during the OFTT to be used for laboratory tests. Results: The case subject had apolipoprotein E (apo-E) phenotype 4/2 with fatty liver but without any cardiovascular disease. His serum TG, HDL-C, apo-AI and apo-B48 levels were significantly higher, but the low-density lipoprotein cholesterol level was lower than controls. Although post-heparin plasma lipoprotein lipase and hepatic lipase (both mass and activity) were nearly normal, the serum level of angiopoietin-like-protein-3 was extremely elevated. While his serum remnant-like particles-TG (RLP-TG) and total TG levels significantly increased after a fat load, the RLP-cholesterol (RLP-C) level did not increase during OFTT. Conclusions: The case subject was different from the common CETP deficient cases reported previously. Also, the results indicated that the metabolic pathways of RLP-C and RLP-TG formation in the postprandial state are controlled independently in CETP deficient cases. CETP deficiency itself may not be atherogenic, while one with elevated RLPs may be atherogenic. These cases may have raised the controversy of whether CETP deficiency is atherogenic or not.

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“…Human in vitro studies have shown that dalcetrapib inhibits CETPmediated transfer of cholesteryl ester from HDL-C to triglyceride-rich lipoproteins [36]. Dalcetrapib inhibits cholesteryl ester transfer to remnant-like lipoprotein particles (RLP) more than transfer to non-RLP, resulting in significant reduction in RLP-C. RLP-C, along with LDL-C, are components of non-HDL-C, the second target of lipid therapy identified by the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III guidelines [7].…”

Section: Introduction To the Compoundmentioning

confidence: 99%

Dalcetrapib: a review of Phase II data

Robinson

2010

Expert Opinion on Investigational Drugs

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Before regulatory approval is granted, results from the ongoing dal-OUTCOMES trial evaluating the effects of dalcetrapib 600 mg daily over standard statin therapy on mortality and morbidity in > 15,000 high-risk CHD patients will be needed. The Dalcetrapib HDL Evaluation, Atherosclerosis and Reverse Cholesterol Transport (dal-HEART) program also includes three surrogate end point trials, dal-VESSEL, dal-PLAQUE and dal-PLAQUE 2, which will provide further information as to the contribution of CETP to cardiovascular disease.

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Cholesteryl ester transfer protein promotes the formation of cholesterol-rich remnant like lipoprotein particles in human plasma

Cited by 19 publications

References 34 publications

Plasma adiponectin is a more specific marker of fatty liver than a marker of metabolic syndrome in Japanese men

Plasma adiponectin is a more specific marker of fatty liver than a marker of metabolic syndrome in Japanese men

A deficiency of cholesteryl ester transfer protein whose serum remnant-like particle-triglyceride significantly increased, but serum remnant-like particle-cholesterol did not after an oral fat load

Dalcetrapib: a review of Phase II data

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