Increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia

Cohn, Jeffrey S.; Tremblay, Michel J.; Batal, Rami; Jacques, Hélène; Rodríguez, Claudia; Steiner, George; Mamer, Orval; Davignon, Jean

doi:10.1016/j.atherosclerosis.2004.06.011

Cited by 56 publications

(60 citation statements)

References 49 publications

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“…Recent epidemiological studies show that apoC-III is an independent predictor of CVD risk and progression in humans (9,40,41), and that its presence on lipoproteins promotes their atherogenicity (8,(43)(44)(45). This is likely because apoC-III, expressed in both liver and the intestine, raises plasma TAG through the inhibition of hepatic clearance of TAG-rich chylomicrons and VLDLs, stimulates VLDL secretion, and modulates intestinal TAG trafficking (12,(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Jattan

Rodia

et al. 2017

Journal of Lipid Research

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The intestine plays a crucial role in regulating wholebody lipid homeostasis through dietary fat absorption and secretion, and through its endocrine secretions of incretin hormones and immune mediators. The intestine synthesizes a specialized lipoprotein, the chylomicron, which contains both dietary triglyceride (TAG) and cholesterol, in addition to both structural and functional apolipoprotein cargo. apoB-48 provides structure to the nascent chylomicron, while apoA-IV, apoA-I, and apoC-III function in the periphery to modify plasma lipid metabolism and clearance, interact with inflammatory apparatus for efficient clearance of dietary lipopolysaccharide and oxidized lipids, and modulate insulin signaling and glucose metabolism (1-3). Therefore, the intestine and its secreted chylomicron are critical regulators of metabolic disease.Despite the importance of the intestine in raising plasma TAG levels in the postprandial state and in apolipoprotein secretion, mechanistic studies are difficult to carry out. This is due to a lack of suitable ex vivo cell culture models that are nontransformed yet stable enough in culture for extended studies and genetic manipulations. The intestine is difficult to model ex vivo because enterocytes are in constant turnover, and are only replenished by intestinal stem cells

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Section: Discussionmentioning

confidence: 99%

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Jattan

Rodia

et al. 2017

Journal of Lipid Research

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“…These studies have been relatively consistent in revealing that plasma apoC-III pool size (PS) and production rate (PR), rather than plasma apoC-III fractional catabolic rate (FCR), were the major determinants of plasma TG levels (13). Other studies have also indicated that apoC-III concentrations and PR were strongly and positively associated with increased production rate of VLDL-TG (14).…”

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confidence: 90%

Apolipoprotein C-III isoforms: kinetics and relative implication in lipid metabolism

Mauger

Couture

Bergeron

et al. 2006

Journal of Lipid Research

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Apolipoprotein C-III (apoC-III) production rate (PR) is strongly correlated with plasma triglyceride (TG) levels. ApoC-III exists in three different isoforms, according to the sialylation degree of the protein. We investigated the kinetics and respective role of each apoC-III isoform in modulating intravascular lipid/lipoprotein metabolism. ApoC-III kinetics were measured in a sample of 18 healthy men [mean age (6SD) 42.1 6 9.5 years, body mass index 29.8 6 4.6 kg/m 2 ] using a primed-constant infusion of L-(5,5,5-D3) leucine for 12 h. Mono-sialylated and di-sialylated apoC-III (apo-CIII 1 and apoC-III 2 ) exhibited similar PRs (means 6 SD, 1.22 6 0.49 mg/kg/day vs. 1.15 6 0.59 mg/ kg/day, respectively) and similar fractional catabolic rates (FCRs) (0.51 6 0.13 pool/day vs. 0.61 6 0.24 pool/day, respectively). Nonsialylated apoC-III (apoC-III 0 ) had an 80% lower PR (0.25 6 0.12 mg/kg/day) and a 60% lower FCR (0.21 6 0.07 pool/day) (P , 0.0001 for comparison with CIII 1 and CIII 2 isoforms). The PRs of apoC-III 1 and apoC-III 2 were more strongly correlated with plasma TG levels (r . 0.8, P , 0.0001) than was apoC-III 0 PR (r 5 0.54, P , 0.05). Finally, the PR of apoC-III 2 was strongly correlated with the proportion of LDL ,255 Å (r 5 0.72, P 5 0.002). These results suggest that all apoC-III isoforms, especially the predominant CIII 1 and CIII 2 isoforms, contribute to hypertriglyceridemia and that apoC-III 2 may play a significant role in the expression of the small, dense LDL phenotype.-Mauger J-F., P. Couture, N. Bergeron, and B. Lamarche. Apolipoprotein C-III isoforms: kinetics and relative implication in lipid metabolism. J. Lipid Res. 2006Res. . 47: 1212Res. -1218 Supplementary key words VLDL metabolism . metabolic syndrome . triglycerides . LDL particle size . sialylation Emphasis is continuously put on plasma triglyceride (TG) levels as a key correlate of many features of the metabolic syndrome, such as abdominal obesity, type 2 diabetes, lower levels of anti-atherogenic HDL-cholesterol (HDL-C), and higher levels of triglyceride-rich lipoproteins (TRLs) (1-3). Increased concentrations of plasma triglycerides are also thought to promote the expression of the type B LDL phenotype, characterized by the predominant presence of more-atherogenic, small, dense LDL particles (4, 5). In that context, there is a renewed interest in better understanding the mechanisms modulating plasma TG levels.Apolipoprotein C-III (apoC-III) is a protein secreted mostly by the liver and, to a lesser extent, by the intestine (3). In circulation, it is associated with both TRLs and HDL (6). ApoC-III is present in three isoforms that are termed apoC-III 0 , apoC-III 1 , and apoC-III 2 , depending on the number of sialic acid molecules (0 to 2) terminating the oligosaccharidic portions of the protein (7). Each isoform has been shown to contribute, respectively, to approximately 10, 55, and 35% of the total apoC-III levels in circulation (8). Total plasma apoC-III levels have been identified as a major determinant of trig...

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“…Recent kinetic studies conducted in humans have suggested that an increased production rather than a decreased catabolism of apoC-III was the most important determinant of plasma TG levels in human subjects and a characteristic feature of patients with hypertriglyceridemia (Cohn et al, 2004b). These results suggest that a pharmacological or dietary treatment that reduces apoC-III production would most likely be effective in lowering plasma TG levels.…”

Section: Introductionmentioning

confidence: 96%

Kinetics of plasma apolipoprotein C-III as a determinant of diet-induced changes in plasma triglyceride levels

Desroches

Deshaies

et al. 2007

Eur J Clin Nutr

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Objective: To compare the effect of a high monounsaturated fatty acid (MUFA) diet and of a control low-fat diet consumed under ad libitum conditions on plasma apolipoprotein (apo) C-III metabolism. Design: Randomized, two-arm parallel dietary trial. Setting: Diets were prepared and consumed at the metabolic kitchen of the Department of Food Sciences and Nutrition, and laboratory analyses were performed at the Institute of Nutraceuticals and Functional Foods at Laval University. Subjects and interventions: Eighteen men were randomly assigned to either the high MUFA diet or the low-fat control diet, which they consumed for 6-7 weeks. Before and after the dietary intervention, subjects received a primed-constant infusion of [5,5,5-D 3 ]-L-leucine for 12 h under constant feeding conditions for the determination of plasma apoC-III kinetics. Results: The high-MUFA diet and the low-fat control diet had no significant impact on plasma apoC-III production rate (PR) or fractional catabolic rate. However, diet-induced variations in plasma apoCIII PR predicted the reduction in plasma triglycerides and apoC-III levels (r ¼ 0.85, Po0.01 and r ¼ 0.73, Po0.05, respectively) in the high MUFA group only. Conclusions: These results suggest that the hypotriglyceridemic effect of a high-MUFA diet may be attributable in part to a reduced hepatic production of apoC-III.

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Increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia

Cited by 56 publications

References 49 publications

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Apolipoprotein C-III isoforms: kinetics and relative implication in lipid metabolism

Kinetics of plasma apolipoprotein C-III as a determinant of diet-induced changes in plasma triglyceride levels

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