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- Aminoff, A, et al.
(författare)
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Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
- 2010
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Ingår i: Journal of lipid research. - 0022-2275 .- 1539-7262. ; 51:1, s. 103-11
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Tidskriftsartikel (refereegranskat)abstract
- Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
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- Andersson, Eva-Lotta, et al.
(författare)
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Bile salt-stimulated lipase and pancreatic lipase-related protein 2 : key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line
- 2011
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Ingår i: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 52:11, s. 1949-1956
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Tidskriftsartikel (refereegranskat)abstract
- In rodents, bile salt-stimulated lipase (BSSL) and pancreatic lipase-related protein 2 (PLRP2) are the dominant lipases expressed in the exocrine pancreas in early life, when milk is the main food. The aim of the present study was to evaluate if BSSL and PLRP2 are also key enzymes in neonatal intestinal fat digestion. Using Caco-2 cells as a model for the small intestinal epithelium, purified human enzymes were incubated in the apical chamber with substrates and bile salt concentrations resembling the milieu of the small intestine of newborn infants. BSSL and PLRP2 hydrolyzed triglycerides (TG) to free fatty acids (FA) and glycerol. The cells took up the FA, which were reesterfied to TG. Together, BSSL and PLRP2 have a synergistic effect, increasing cellular uptake 4-fold compared to the sum of each lipase alone. A synergistic effect was also observed with retinyl ester as a substrate. PLRP2 hydrolyzed cholesteryl ester but not as efficiently as BSSL, and the two had an additive rather than synergistic effect. We conclude the key enzymes in intestinal fat digestion are different in newborns than later in life. Further studies are needed to fully understand this difference and its implication for designing optimal neonatal nutrition.
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- Bendsen, Nathalie T., et al.
(författare)
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Effect of industrially produced trans fat on markers of systemic inflammation : evidence from a randomized trial in women
- 2011
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 52:10, s. 1821-1828
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Tidskriftsartikel (refereegranskat)abstract
- Consumption of industrially produced trans fatty acids (IP-TFA) has been positively associated with systemic markers of low-grade inflammation and endothelial dysfunction in cross-sectional studies, but results from intervention studies are inconclusive. Therefore, we conducted a 16 week double-blind parallel intervention study with the objective to examine the effect of IP-TFA intake on bio-markers of inflammation, oxidative stress, and endothelial dysfunction. Fifty-two healthy overweight postmenopausal women (49 completers) were randomly assigned to receive either partially hydrogenated soybean oil (15.7 g/day IP-TFA) or control oil without IP-TFA. After 16 weeks, IP-TFA intake increased baseline-adjusted serum tumor necrosis factor (TNF) alpha by 12% [95% confidence interval (CI): 5-20; P = 0.002] more in the IP-TFA group compared with controls. Plasma soluble TNF receptors 1 and 2 were also increased by IP-TFA [155 pg/ml (CI: 63-247); P < 0.001 and 480 pg/ml (CI: 72-887); P = 0.02, respectively]. Serum C-reactive protein, interleukin (IL) 6 and adiponectin and subcutaneous abdominal adipose tissue mRNA expression of IL6, IL8, TNF alpha, and adiponectin as well as ceramide content were not affected by IP-TFA, nor was urinary 8-iso-prostaglandin-F(2 alpha). In conclusion, this dietary trial indicates that the mechanisms linking dietary IP-TFA to cardiovascular disease may involve activation of the TNF alpha system.
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