Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles.

Aalto‐Setälä, Katriina; Fisher, Edward A.; Chen, X; Chajek-Shaul, Tova; Hayek, Tony; Zechner, Rudolf; Walsh, Annemarie; Ramakrishnan, R; Ginsberg, Henry N.; Breslow, Jan L.

doi:10.1172/jci116066

Cited by 422 publications

(348 citation statements)

References 54 publications

(17 reference statements)

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“…RBP4 is a transporter protein for retinol that serves as a precursor for the synthesis of ligands of the retinoid X receptor and retinoic acid receptor nuclear hormone receptors [19]. In previous studies, retinoids increased the hepatic production of VLDL [20] and elevated the levels of apolipoprotein (apo) C-III [21], a hepatic protein that delays (1) the catabolism of VLDL particles by inhibiting their binding to the endothelial surface and (2) lipolysis by lipoprotein lipase [22]. This may explain the lack of an association between RBP4 and lipoprotein lipase in our study.…”

Section: Discussionmentioning

confidence: 99%

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

et al. 2007

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Aims/hypothesis Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. Methods Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. Results RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA 1c in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDLcholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDLcholesterol and plasma triacylglycerol. Conclusions/interpretation RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

et al. 2007

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“…The genetically determined deficiency of apo-CIII has been shown to increase the rate of TG clearance from plasma by 6-to 7-fold (31). Over-expression of apo-CIII produces hypertriglyceridemia in transgenic mouse models via inhibition of clearance of TG-rich particles (32). It is now clear that normal physiological systems responsible for TG transport are partially determined by the plasma concentration of apo-CIII (33).…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Parzianello

Oliveira

Coelho

2008

Braz J Med Biol Res

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Apolipoprotein CIII (apo-CIII) participates in the regulation of triglyceride-rich lipoprotein metabolism. Several polymorphic sites have been detected within and around the apo-CIII gene. Here, we examined the relationship between apo-CIII Sst I polymorphism (CC, CG, GG genotypes) and plasma triglyceride (TG) levels in a group of 159 Japanese individuals living in Southern Brazil. The sample was divided into a group of Japanese descendants (N = 51) with high TG (HTG; >200 mg/dL) and a group of Japanese descendants (N = 108) with normal TG (NTG; <200 mg/dL). TG and total cholesterol levels were analyzed by an enzymatic method using the Labtest-Diagnostic kit and high-and low-density lipoproteins by a direct method using the Labtest-Diagnostic kit and DiaSys Diagnostic System International kit, respectively. A 428-bp sequence of apo-CIII gene was amplified using oligonucleotide primers 5' GGT GAC CGA TGG CTT CAG TTC CCT GA 3' and 5' CAG AAG GTG GAT AGA GCG CTG GCC T 3'. The PCR products were digested with a restriction endonuclease Sst I. Rare G allele was highly prevalent in our study population (0.416) compared to Caucasians (0.00-0.11). G allele was almost two times more prevalent in the HTG group compared to the NTG group (P < 0.001). The genotype distribution was consistent with the Hardy-Weinberg equilibrium. There was a significant association between rare G allele and HTG in Japanese individuals living in Southern Brazil as indicated by one-way ANOVA, P < 0.05.

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“…Since ApoC-III induces an increase in plasma TG levels [36], this may be an additional factor contributing to dyslipidemia in CKD.…”

Section: Apolipoprotein C3 (Apoc-iii)mentioning

confidence: 99%

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Khurana

Silverstein

2015

Pediatr Nephrol

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Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Children with chronic kidney disease (CKD) and end-stage renal disease (ESRD) exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high, being present in 39-65 % of patients. Elevated lipid levels in children without renal disease are a risk factor for cardiovascular disease (CVD), while the risk for CVD in pediatric CKD/ESRD is unclear. The pathogenesis of dyslipidemia in CKD features various factors, including increased levels of triglycerides, triglyceride-rich lipoproteins, apolipoprotein C3 (ApoC-III), decreased levels of cholesterylester transfer protein and high-density lipoproteins, and aberrations in serum very low-density and intermediatedensity lipoproteins. If initial risk assessment indicates that a child with advanced CKD has 2 or more co-morbidities for CVD, first-line treatment should consist of nonpharmacologic management such as therapeutic lifestyle changes and dietary counseling. Pharmacologic treatment of dyslipidemia may reduce the incidence of CVD in children with CKD/ESRD, but randomized trials are lacking. Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Lipids are generally categorized by their density and other physical characteristics [1]. Since lipids such as cholesterol and triglycerides (TG) are insoluble in plasma, lipoproteins are required to transport all sources (e.g., diet) of lipids to areas in which the lipids can either be stored for future use or used immediately [2], although it should be noted that short-and medium-chain fatty acids also flow via the portal system as fatty acids. Specifically, low-density lipoproteins (LDL) carry the majority of cholesterol (forming LDL-C), while very low-density lipoproteins (VLDL) carry the majority of triglycerides.The broad categories of lipoproteins are chylomicrons, VLDL, LDL, and high-density lipoproteins (HDL Prevalence and sub-types of dyslipidemia in pediatric chronic kidney disease (CKD) and end-stage renal disease (ESRD)Children with CKD/ESRD exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high (39-65 %), but is significantly dependent on the cause and vintage of CKD (e.g., usually more common and severe with glomerular disease and proteinuria) and the stage of the disease [4,5]. The Chronic Kidney Disease in Children (CKiD) study included an assessment of the relationship between renal function and serum lipid levels. The most common type of dyslipidemia was hypertriglyceridemia. They found an inverse relationship between renal function (measured glomerular filtration rate, or GFR) and serum TG and total cholesterol (TC) levels; that is, as GFR declines, TG and TC levels generally increase. Conversely, there is a ...

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Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles.

Cited by 422 publications

References 54 publications

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

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