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1.
Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference 总被引:1,自引:0,他引:1
Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has
been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. New findings
suggest that eicosapentaenoic acid (EPA), and not docosahexaenoic acid (DHA), lowers plasma triacylglycerol by increased mitochondrial
fatty acid oxidation and decreased availability of fatty acids for triacylglycerol synthesis. To contribute to the understanding
of the triacylglycerol-lowering mechanism of fish oil, the different metabolic properties of EPA and DHA were studied in rat
liver parenchymal cells and isolated rat liver organelles. EPA-CoA was a poorer substrate than DHA-CoA for DGAT in isolated
rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[3H]glycerol/diacyl[3H]glycerol ratio was observed. The distribution of [1-14C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not
DHA) in rat liver parenchymal cells. [1-14C]EPA was oxidized to a much greater extent than [1-14C]DHA in rat liver parenchymal cells, isolated peroxisomes, and especially in purified mitochondria. As the oxidation of EPA
was more effective and sensitive to the CPT-I inhibitor, etomoxir, when measured in a combination of both mitochondria and
peroxisomes, we hypothesized that both are involved in EPA oxidation, whereas DHA mainly is oxidized in peroxisomes. In rats,
EPA treatment lowered plasma triacylglycerol and increased hepatic mitochondrial fatty acid oxidation and carnitine palmitoyltransferase
(CPT)-I activity in both the presence and absence of malonyl-CoA. Whereas only EPA treatment increased the mRNA levels of
CPT-I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl-CoA oxidase and fatty acid binding protein more effectively
than EPA treatment. In conclusion, EPA and DHA affect cellular organelles in relation to their substrate preference. The present
study strongly supports the hypothesis that EPA, and not DHA, lowers plasma triacylglycerol by increased mitochondrial fatty
acid oxidation. 相似文献
2.
Reduced secretion of triacylglycerol in CaCo-2 cells transfected with intestinal fatty acid-binding protein 总被引:1,自引:0,他引:1
The fatty acid-binding proteins are hypothesized to be involved in cellular fatty acid transport and trafficking. We established
CaCo-2 cells stably transfected with intestinal fatty acid-binding protein (I-FABP) and examined how the expression of this
protein may influence fatty acid metabolism. I-FABP expression was detectable in I-FABP-transfected cells, whereas parent
CaCo-2 cells as well as mock-transfected cells failed to express detectable levels of I-FABP mRNA or protein at any stage
of differentiation. For studies of lipid metabolism, cells were incubated with [14C]oleic acid in taurocholate micelles containing monoolein, and distribution of labeled fatty acid in cellular and secreted
lipids was examined. In one transfected cell clone, expressing the highest level of I-FABP, labeled cellular triacylglycerol
increased approximately twofold as compared to control cells. The level of intracellular triacylglycerol in two other I-FABP-transfected
clones resembled that of control cells. However, secretion of triacylglycerol was markedly reduced in all the I-FABP-expressing
cell lines. Our data suggest that increased expression of I-FABP leads to reduced triacylglycerol secretion in intestinal
cells. 相似文献
3.
An overview of JML tools and applications 总被引:3,自引:0,他引:3
Lilian Burdy Yoonsik Cheon David R. Cok Michael D. Ernst Joseph R. Kiniry Gary T. Leavens K. Rustan M. Leino Erik Poll 《International Journal on Software Tools for Technology Transfer (STTT)》2005,7(3):212-232
The Java Modeling Language (JML) can be used to specify the detailed design of Java classes and interfaces by adding annotations to Java source files. The aim of JML is to provide a specification language that is easy to use for Java programmers and that is supported by a wide range of tools for specification typechecking, runtime debugging, static analysis, and verification.This paper gives an overview of the main ideas behind JML, details about JML’s wide range of tools, and a glimpse into existing applications of JML. 相似文献
4.
AC Rustan B Halvorsen AC Huggett T Ranheim CA Drevon 《Canadian Metallurgical Quarterly》1997,17(10):2140-2149
We studied the effect of the coffee diterpene alcohols, cafestol and kahweol, on cholesterol metabolism in HepG2 cells. Uptake of 125I-tyramine cellobiose-labeled LDL was decreased by 15% to 20% (P < .05) after 18 hours of preincubation with cafestol (20 micrograms/mL), whereas 25-hydroxycholesterol reduced uptake by 55% to 65% (P < .05). Degradation of LDL in the presence of cafestol was decreased by 20% to 30% (P < .05) under the same conditions. The effect of cafestol (20 micrograms/mL) on uptake and degradation of LDL was greatest (35% to 40%, P < .05) after 6 and 10 hours of preincubation, respectively. Furthermore, the effect of cafestol was also dependent on its concentration, and a significant decrease in the LDL uptake (19%) was observed at 10 micrograms/mL (P < .05). Specific binding of LDL was reduced by 17% (P < .05) and 60% (P < .05) after preincubation with cafestol (20 micrograms/mL) and 25-hydroxycholesterol (5 micrograms/mL) for 6 hours, respectively, compared with control cells. Analysis of LDL binding showed that cafestol reduced the number of binding sites for LDL on the cell surface (capacity) by 35% (P < .05). In contrast, no significant effect on the level of mRNA for the LDL receptor was observed after incubation with cafestol, whereas 25-hydroxycholesterol reduced the mRNA level for the LDL receptor by 40% to 50% (P < .05). A fusion gene construct consisting of a synthetic sterol regulatory element-1 (SRE-1) promoter for the human LDL receptor coupled to the reporter gene for chloramphenicol acetyltransferase (CAT) was transfected into HepG2 cells. No change was observed in CAT activity in SRE-1-transfected cells after incubation with cafestol, whereas 25-hydroxycholesterol reduced CAT activity by 30% to 40% (P < .05). Incorporation of [14C]acetate into unesterified cholesterol and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were unaffected in cells incubated with cafestol as well as the cafestol-kahweol mixture compared with control cells. Moreover, cafestol and the cafestol-kahweol mixture did not promote increased incorporation of radiolabeled [14C]oleic acid into cholesteryl esters after short-term incubation compared with control cells. On the other hand, 25-hydroxycholesterol caused a 70% to 90% reduction of cholesterol synthesis (P < .05) and HMG-CoA reductase activity (P < .05), decreased HMG-CoA reductase mRNA level by 70% to 80% (P < .05), and promoted a twofold increase in cholesterol esterification (P < .05). Finally, no effect of the coffee diterpenes on bile acid formation was observed. These results suggest that cafestol (and kahweol) may reduce the activity of hepatic LDL receptors and thereby cause extracellular accumulation of LDL. 相似文献
5.
6.
K. Rustan M. Leino 《Formal Aspects of Computing》1999,11(1):56-74
A permutation can be encoded in several different ways. This paper discusses some relations among some encodings and how
one can be computed from others. The paper shows a short proof of an existing efficient algorithm for encoding a permutation
and presents two new efficient algorithms. One of the new algorithms is constructed as the inverse of an existing algorithm
for decoding, making it the first efficient permutation encoding algorithm obtained in that way.
Received June 1994 / Accepted in revised form December 1998 相似文献
7.
Tranheim Kase E Nikolić N Pettersen Hessvik N Fjeldheim AK Jensen J Thoresen GH Rustan AC 《Lipids》2012,47(5):483-493
This study explores the pharmacokinetics of 22-S-hydroxycholesterol (22SHC) in vivo in rats. We also carried out a metabolic study to explore whether the beneficial effects
observed of 22SHC on glucose and lipid metabolism in vitro could be seen in vivo in rats. In the pharmacokinetic study, rats
were given 50 mg/kg of [3H]22-S-hydroxycholesterol before absorption, distribution and excretion were monitored. In the metabolic study, the effect of 22SHC
(30 mg/kg/day for 3 weeks) in rats on body weight gain [chow and high-fat diet (HFD)], serum lipids triacylglycerol (TAG)
content and gene expression in liver and skeletal muscle were examined. Results showed that 22SHC was well absorbed after
oral administration and distributed to most organs and mainly excreted in feces. Rats receiving 22SHC gained less body weight
than their controls regardless whether the animals received chow diet or HFD. Moreover, we observed that animals receiving
HFD had elevated levels of serum TAG while this was not observed for animals on HFD supplemented with 22SHC. The amount of
TAG in liver was reduced after 22SHC treatment in animals receiving either chow diet or HFD. Gene expression analysis revealed
that two genes (carnitine palmitoyltransferase 2 and uncoupling protein 3) involved in fatty acid oxidation and energy dissipation
were increased in liver. Ucp3 expression (both protein and mRNA level) was increased in skeletal muscle, but insulin-stimulated
glucose uptake and TAG content were unchanged. In conclusion, 22SHC seems to be an interesting model substance in the search
of treatments for disorders involving aberrations in lipid metabolism. 相似文献
8.
Generalizing the notion of function composition, we introduce the concept ofconditional function composition and present a theory of such compositions. We use the theory to describe the semantics of a programming language with exceptions, and to relate exceptions to theIF statement.Supported in part by Air Force Office of Scientific Research grant number 91-0070. Now at DEC Systems Research Center, Palo Alto, CA. 相似文献
9.
The mechanisms behind the hypolipidemic effect of two sulfur-substituted fatty acid analogues, 3-thiadicarboxylic acid and
tetradecylthioacetic acid, have been investigated in cultured hepatocytes. There was a dose-dependent reduction in incorporation
of [3H]water into triacylglycerol and diacylglycerol when tetradecylthioacetic acid was added to rat hepatocytes cultured in the
presence of 200 μM oleic acid. Tetradecylthioacetic acid also increased the oxidation of [14C]palmitic acid compared to oleic acid, inhibited the incorporation of radiolabeled precursors into diacylglycerol to a greater
extent than into triacylglycerol, and reduced the secretion of triacylglycerol more than its synthesis. A stimulation, rather
than a reduction, in glycerolipid synthesis and secretion by tetradecylthioacetic acid was observed when oleic acid was omitted
from the culture medium. When 3-thiadicarboxylic acid was added to cultured hepatocytes, the effects on glycerolipid synthesis
were generally similar to those observed with tetradecylthioacetic acid, but 3-thiadicarboxylic acid did not increase the
oxidation of [14C]palmitic acid. The two fatty acid analogues also had different effects on the synthesis and secretion of cholesterol and
cholesteryl esters—3-thiadicarboxylic acid reduced the incorporation of [3H]water into synthesized and secreted cholesterol and cholesteryl esters, whereas tetradecylthioacetic acid only reduced the
secretion of cholesteryl esters without affecting its synthesis. It is concluded that tetradecylthioacetic acid increases
the oxidation of fatty acids and reduces the synthesis and secretion of glycerolipids. 3-Thiadicarboxylic acid reduces the
synthesis and secretion of both glycerolipids and cholesterol to approximately the same extent without a concomitant increase
in the oxidation of fatty acids. 相似文献
10.
Parosh Aziz Abdulla K. Rustan M. Leino 《International Journal on Software Tools for Technology Transfer (STTT)》2013,15(2):85-88
Developing tools that are able to perform automatic verification on realistic models of software systems is one of the main challenges facing the formal methods community. We briefly review the research area and introduce three papers selected from the Seventeenth International Conference on Tools and Algorithms for the Construction and Analysis of Systems (tacas 2011). 相似文献