![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, 7369 School of Pharmacy, Université Catholique de Louvain, 73 B-1200 Brussels, Belgium
3To whom correspondence should be addressed.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
KEY WORDS: • lipogenesis • triglycerides • fructans • liver • rats • oligofructose
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
). Experimental data support the hypothesis that an
increase in postprandial TAG and lipoprotein remodeling is associated
with atheroma deposition and coronary events in hyperlipidemic,
diabetic and obese subjects, but the relationships among dietary
intake, postprandial response and pathologic events remain to be
clarified (Lairon 1996
). A well-established
association exists between chronic hyperinsulinemia and
hypertriglyceridemia. Insulin appears to be a key hormone in the
regulation of TAG-VLDL secretion. Its influence is dependent on the
nutritional state, i.e., insulin stimulates TAG secretion by perfused
liver of fed rats, but inhibits it in the liver from food-deprived
or insulin-deficient rats (Zammitt et al. 1999
).
Studies have been conducted to identify specific nutrients that would
contribute to the regulation of lipid homeostasis in obesity.
Interestingly, some dietary components that completely escape digestion
can modulate serum lipid concentrations. Oat bran, through its
interaction with bile acid metabolism, is an effective
hypocholesterolemic agent (Lia et al. 1997
). In addition
to their effects in the gastrointestinal tract, several nondigestible
but fermentable carbohydrates have been shown to exert systemic effects
by modifying lipid metabolism. Resistant starch, for example, lowers
plasma cholesterol and TAG concentrations in hamster or rats
(Levrat et al. 1996
, Trautwein et al. 1999
, Younes et al. 1995
). The modulation of
lipoprotein profile (decrease in LDL cholesterol and increase in HDL
cholesterol) by resistant starch was also shown in hypercholesterolemic
patients; this effect seems dependent on the activity of colonic
microflora (Jenkins et al. 1999
). In previous studies,
we demonstrated that the addition of oligofructose (OFS) to the diet of
male Wistar rats decreased serum and hepatic TAG levels
(Delzenne and Kok 1998
, Kok et al. 1996
).
OFS is a nondigestible oligomer of ß-D-fructose, obtained
by enzymatic hydrolysis of inulin extracted from chicory root; these
fructans are also present in vegetables such as onions, artichoke,
asparagus and garlic. OFS is highly fermented in the cecocolon, in both
human and rodents, leading to the selective proliferation of
bifidobacteria [for review, see Roberfroid and Delzenne (1998)
]. In rats, the addition of OFS to a standard diet
enriched in saccharose decreases both serum and hepatic TAG by reducing
de novo fatty acid synthesis in the liver (Agheli et al. 1998
, Kok et al. 1996
). This phenomenon is due
mainly to a decrease in the expression and activity of key lipogenic
enzymes such as fatty acid synthase (FAS) (Delzenne and Kok 1998
). The hypotriglyceridemic effect of OFS has also been
observed in rats and hamsters fed a fat- and cholesterol-rich diet;
such effects could be attributed to extrahepatic events such as the
modulation of bile acid metabolism or an increase in the catabolism of
triglyceride-rich lipoproteins in the circulation (Kok et al. 1998b
, Trautwein et al. 1998
).
Could fructans like OFS, through their influence on lipid homeostasis,
be considered as "functional foods" beneficial for human health?
Several papers support their beneficial influence on serum lipids in
humans (Jackson et al. 1999
), but a recent study did not
show any influence of fructans on circulating TAG in patients with type
2 diabetes (Alles et al. 1999
). Analysis of the effect
of dietary supplementation with fructans in models mimicking metabolic
alterations occurring in obese/noninsulin-dependent diabetes mellitus
(NIDDM) patients is therefore important. This study was designed to
characterize the metabolic effects of supplementing OFS to the diet of
obese male Zucker rats with a genetic deficiency in the leptin
receptor, leading to insulin resistance and preferential utilization of
carbohydrates toward fatty acid storage as TAG in the liver and adipose
tissue.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Genetically obese Zucker (fa/fa) male rats, weighing 140
± 10 g at the beginning of the experiment, were obtained
from Iffa Credo (Les Oncins, France) 5 wk after birth. All animals
received care in compliance with institutional guidelines from the NIH
(NRC 1985)
. Rats were housed in individual cages in a room with
temperature control and an automatic light:dark cycle (lights on from 0700 to 1900h). Rats were randomly assigned to one of the two
groups. Control rats were given free access to a powdered nonpurified
standard diet obtained from a commercial source (UAR AO4, UAR
Villemoisson-sur-Orge, France). This diet contained the following
(g/100 g dry weight): 19% protein (consisting of an equivalent mix of
soy and fish proteins); 70% total carbohydrates obtained from corn,
wheat, barley and bran (containing 3% saccharose and 5% cellulose);
3.2% total lipids; 7.3% minerals and vitamins; 0.32% methionine; and
0.04% choline. OFS-fed rats were fed the same diet containing
100 g raftilose P95/kg. The energy value for the
control and OFS diet was 13.86 and 13.08 kJ/g, respectively. Body
weight and food intake were monitored two times per week. Serum
metabolites were measured during the experiment in rats in the
postprandial state, i.e., at 0900 h and after 9 h food
deprivation in the afternoon, at 1700 h.
After 8 wk of treatment, an oral glucose and lipid tolerance test was
performed according to the procedure described by Iritani et al. 1999
. Food was removed 24 h before the test; the rats were
fed by gavage a glucose load (2 g/kg body) followed by a lipid load (5
g corn oil/kg). Corn oil was commercially available and the fatty acid
composition (g/100 g fatty acids) was as follows: myristic acid 0.6;
palmitic acid 13.4; stearic acid 2.2; palmitoleic acid 0.3; oleic acid
28.7; linoleic acid 47.8; and linolenic acid 1.5. Glucose, triglyceride
and insulin concentrations in plasma were determined using blood
obtained from the tail vein.
After 10 wk of treatment, at 0900 h (corresponding to the postprandial period), all rats were anesthetized with pentobarbital (60 mg/kg body). Blood was collected from the cava and portal veins. Some liver samples were clamped immediately in liquid nitrogen and kept at -80°C. Some pieces were frozen in isopentane, then cut cryostatically for histochemical fat staining with Sudan 7b. Some liver specimens were fixed in 10% formalin, embedded in paraffin and cut with a microtome for hematoxylin and eosin staining.
Chemicals.
Raftilose P95 (Raffinerie Tirlemontoise, Tienen, Belgium), a mixture of glucosyl-(fructosyl)n-fructose and (fructosyl)m-fructose with an average degree of polymerization of 4–8, was used as the fructan source.
Analytical procedures.
Triglycerides, phospholipids, total cholesterol and glucose
concentrations were measured in the serum with the use of kits coupling
enzymatic reaction and spectrophotometric detection of reaction end
products (Triglycerides ESPAS, Phospholipids-PAP, Cholesterol PAP
and Glucose PAP, Elitech, Brussels, Belgium). The same kits were used
for liver lipid analysis, after a chloroform-methanol extraction
according to Folch et al. (1957)
. Insulin concentrations
were determined on frozen plasma samples using a RIA kit from CIS bio
international (Insulin-CT, Oris group, Gif-sur-Yvette, France).
Fatty acid synthase (FAS) activity was measured according to the method
of Linn (1981)
. ATP citrate lyase (ATPCL) and malic
enzyme (ME) activities were measured in the cytosolic fractions
according to Takeda et al. (1969)
and Hsu and Lardy (1969)
, respectively. The esterification pathway
was assessed by measuring phosphatidate phosphohydrolase (PAP) activity
as described by Cheng and Saggerson (1978)
. Protein
concentration was measured by the method of Lowry et al. (1951)
, using bovine serum albumin as standard.
Total RNA was isolated from frozen liver (200 mg) by using the RNAgent total RNA isolation system (Promega, Leiden, Netherlands). The quantification of FAS mRNA was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) as described in the RT-PCR system kit (Promega, Leiden, Netherlands). Amplification was carried out under standard cycling conditions. Specific primer pairs were as follows: 1) FAS, sense 5'- CCAGGCTGTGGAACACAGTGATGGAAC-3' and anti sense 5'-CCAGGCTGTGGAACACAGTGATGGAAC-3'; and 2) ß-actin, sense 5'-CTGACCGAGCGTGGCTACAG-3' and anti sense 5'-GGTGCTAGGAGCCAGGGCAG-3'. Cycle numbers used for each primer pair were adjusted to ensure linear amplification. Reaction products were separated on 1.8% agarose gel in TAE buffer (2 mol/L Tris base; 5.7% acetic acid; 0.05 EDTA, pH 8) containing 0.1 g/L ethidium bromide. RT-PCR products were visualized under short-wave UV light and photographed. Photographs were scanned and the density of the bands was calculated using the program Image Master (Pharmacia Biothec Benelux, Roosendaal, The Netherlands). The FAS/ß-actin mRNA ratio was used as a relative estimate of FAS mRNA abundance.
Statistical analysis.
Data are presented as means ± SEM. Data were analyzed by two-way ANOVA when testing for the interaction of time and treatment. Student’s t test was applied to compare results at one particular time point. StatView512+ (Abacus Concepts, Berkeley, CA) was used as software. The level of significance was set at P < 0.05.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
). Body weight gradually increased with time but it was significantly
lower in OFS than in control rats (P < 0.05) after 4
wk of treatment. At the end of the study, body weight was
±10% lower in OFS-fed than in control rats (Table 1
).
|
|
) was significantly lower in OFS than in
control rats mainly at the beginning of the study; the difference
between groups gradually disappeared with time from wk 4. Serum triglyceride concentrations increased gradually with time during the study in both the control and OFS-fed rats. In the postprandial state, TAG levels started at 0.71 ± 0.04 mmol/L and reached 2.95 ± 0.37 mmol/L in control rats within 7 wk of treatment. They increased from 0.68 ± 0.10 to 3.43 ± 0.3 mmol/L in OFS-fed rats. In food-deprived rats, TAG concentrations reached 2.72 ± 0.29 and 3.09 ± 0.35 mmol/L in control and OFS-fed rats, respectively. No significant differences in glycemia were observed between groups when measured in the postprandial or food-deprived states (data not shown).
After 8 wk of treatment, we evaluated the putative effect of OFS on
glycemia and triglyceridemia, after an oral load in glucose and lipids,
in rats that had been deprived of food for 24 h. Within 1 h
after gavage, triglyceridemia decreased in both control and OFS-fed
rats; between 1 and 2 h, a large increase in serum triglyceridemia
was observed, which was significantly higher in OFS-fed than in
control rats (Fig. 2A
) (P = 0.0024). The areas under the curves between 1 and
5 h were 16.34 ± 0.65 and 24.76 ± 1.52
mmol/(L · h) for control and OFS-fed rats, respectively
(P = 0.001). Glycemia peaked at 30 min, and returned to
basal values within 2 h (Fig. 2B
). Control and
OFS-fed groups did not differ. The evolution of insulinemia also
did not differ between OFS-fed and control rats (Fig. 2C
) (P = 0.08).
|
At the end of the study, glycemia was significantly lower than controls
in both the portal and the cava veins of OFS-fed rats (Table 2
). Serum insulin was 100% greater in the OFS group compared with
controls, but differences were not significant (P = 0.120) due to interindividual variability. Phospholipemia,
triglyceridemia and cholesterolemia did not differ between groups
(Table 2)
.
|
Liver weight was 20% lower in OFS-fed rats than in controls
(P = 0.002) (Table 1)
. Hepatic triglyceride
concentration was 57% lower in OFS-fed rats compared with control
rats (P = 0.04), and hepatic PL concentration was also
lower (P = 0.04). This was confirmed by histologic
examination of the liver (Fig. 3
). Fat staining performed on cryostat section in controls (Fig. 3A
) showed numerous micro- and macrovacuolar Sudan 7b
positive hepatocytes, which were present mainly in the midzonal,
partially in the periportal area of the hepatic lobule. Fewer fat
positive cells were found in the liver of OFS-treated rats (Fig. 3B
); these cells were dispersed mainly in the periphery of
the midzonal area. This difference in fatty degeneration of hepatocytes
between Zucker rats fed control and OFS-containing diets, was also
visible after hematoxylin and eosin staining (white vacuoles) (Fig. 3C
and Fig. 3D
).
|
, as was that of PAP, a key enzyme
controlling fatty acid esterification. Only malic enzyme activity was
significantly lower in OFS-fed rats than in controls. FAS mRNA
levels did not differ between groups. |
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
,
Diehl 1999
, Purnell and Brunzell 1997
).
Our previous studies used nonobese rats; other results obtained in
hypertriglyceridemic nonobese patients suggest that the supplementation
of diets with some specific nutrients such as nondigestible fructans
could be helpful in the control of TAG metabolism (Delzenne and Kok 1999
, Fiordaliso et al. 1995
, Jackson et al. 1999
, Kok et al. 1996
and 1998a
and 1998b
). Our work was designed to analyze the putative
influence of dietary supplementation with a nondigestible fructan,
oligofructose, in obese fa/fa Zucker rats, which develop
hypertriglyceridemia associated with muscle insulin resistance and
obesity (Penicaud et al. 1987
). The addition of 10% OFS
to the standard diet of male Zucker rats slowed the increase in body
weight, an effect that was not shown in previous experiments performed
in nonobese rats receiving the same dose of OFS (Delzenne and Kok 1998
, Fiordaliso et al. 1995
). This effect
was significant after 4 wk of treatment, whereas the inhibitory effect
of OFS on food and energy intake was significant during the first few
weeks of treatment only. At the end of the treatment (10 wk), body
weight was ±10% lower in OFS than in controls rats. Interestingly, a
significantly lower epididymal fat mass was observed in OFS-fed
rats.
The influence of OFS on lipemia and glycemia in Zucker rats varied with
the duration of the treatment. In contrast to the results obtained in
rats fed OFS in either standard or lipid-rich diets, in which a
lower triglyceridemia was observed from wk 1 of treatment (Kok et al. 1996
and 1998a
), serum TAG were not modified by
OFS treatment in either the postprandial or food-deprived state. A
glucose and lipid load test was performed after 8 wk of treatment. The
increase in triglyceridemia occurring 2 h after an oral load of
glucose and corn oil was significantly higher in OFS-fed than in
controls rats, suggesting either a higher capacity to absorb lipids
from the intestinal tract and/or a greater secretion of endogenous VLDL
from the liver. The putative promoting effect of OFS on lipid
absorption is disturbing because it is generally accepted that dietary
fiber promotes the fecal excretion of bile acids and thus interferes
with the absorption of dietary lipids. However, some investigators have
obtained results suggesting that the intestinal activity of lipase and
the secretion of bile acids, two processes participating in TAG
digestion, are higher in rats fed a diet containing fermentable fibers
such as guar gum or pectin (Favier et al. 1997
,
Foreman and Scheemann 1982
, Levrat et al.
2000
). Could such a mechanism also occur in OFS-fed rats?
The question remains open. What about a putative effect on VLDL
secretion? This question will be discussed below.
Knowing the putative atherogenic role of postprandial
hypertriglyceridemia in humans, it is essential to clarify the
mechanism and the putative relevance in humans of the higher
triglyceridemia observed in OFS-treated rats after a fat load.
After 10 wk of treatment, serum TAG and cholesterol levels, measured in
the cava and portal veins, were similar in control and OFS-fed
rats. However, OFS feeding led to a dramatic decrease in the
concentration of TAG in liver. This phenomenon, which reduced the
relative liver weight, was confirmed by histologic analysis. In Zucker
rats fed the standard diet, accumulation of lipid vacuoles, stained by
Sudan 7b, was observed mainly in the midzonal area and partially in the
periportal zone of the liver lobule, as previously shown by
Koneru et al. (1995)
. The phenomenon was much less
dramatic in the liver of rats fed OFS, in which only rare enlarged
fat-containing hepatocytes were dispersed, mainly in the periphery
of the midzonal area.
Obese Zucker rats develop hepatic steatosis due to excessive synthesis
and storage of TAG in the liver (Fukuda et al. 1982
).
Therefore, we measured the activities of key enzymes involved in fatty
acid synthesis (ME, ATPCL and FAS) and esterification (PAP). The only
significant effect was a lower activity of ME, which provides NADPH for
fatty acid elongation by FAS complex in OFS-fed rats, whereas the
other enzyme activities and FAS mRNA were not different. This effect
differed from the huge decrease in lipogenic enzyme mRNA and activities
observed in the liver of OFS-fed Wistar rats (Delzenne and Kok 1999
). Glucose and insulin are important regulators of
fatty acid synthesis because they coordinately promote lipogenic enzyme
gene expression (Girard et al. 1997
). Postprandial
insulin was significantly lower in nonobese rats fed
fructan-enriched diets, in which hepatic lipogenesis was strongly
inhibited (Kok et al. 1998b
). Is the present
study, we did not detect any modifications of glycemia during OFS
treatment, but a lower serum glucose concentration was observed in the
portal and cava veins at the end of the study in OFS-fed rats. This
effect was accompanied by a higher concentration of insulin. Although
the role of insulin as a regulator of VLDL secretion is controversial,
several studies support its role as a promoter of VLDL secretion from
liver tissue in vivo and in vitro (Zammitt 1996
). A
higher secretion of VLDL in Zucker rats treated with OFS could explain
the lower TAG accumulation in the liver. This hypothesis remains to be
tested. De novo lipogenesis is not the sole source of fatty acids for
TAG synthesis in the liver. In Zucker rats, the large fat mass releases
nonesterified fatty acids that reach the liver. We have shown that the
epididymal fat mass is lower in OFS-fed rats, but the postprandial
and post- food deprivation concentrations of nonesterified fatty acids
in the serum was not modified by the treatment, at least until wk 5
(data not shown).
The mechanism by which such nondigestible carbohydrate such as
oligofructose may modulate systemic lipid metabolism remains unknown.
It could be related to the lower food and energy intakes at the
beginning of the treatment, or to OFS fermentation in the ceco-colon. A
possible role of the microflora in providing a hepatotrophic factor or
in modifying their bioavailability would be interesting to test. On the
other hand, short-chain carboxylic acids such as acetate and
propionate are end products of bacterial fermentation of fructans,
which reach the liver through the portal vein. Some in vitro studies
indicate that both acetate and propionate have antagonistic effects on
lipid metabolism (acetate is a lipogenic substrate, whereas propionate
is an effective inhibitor of lipid synthesis in isolated hepatocytes)
(Demigné et al. 1995
and 1999
). Their putative
role as regulators of TAG synthesis and secretion in the liver of obese
Zucker rats remains to be evaluated.
In conclusion, this study suggests that the metabolic response to
dietary fructans is different in obese Zucker rats than in other animal
models. They do not have the hypotriglyceridemia observed in numerous
studies of animals and humans (Roberfroid and Delzenne 1998
). This study suggests that fructans do not counteract the
hyperlipidemia associated with insulin resistance due to a
leptin-receptor defect. This could explain why some authors failed
to find a hypotriglyceridemic effect of fructans in diabetic patients
(Alles et al. 1999
). However, we found that dietary
fructan supplementation counteracted both fat mass development and the
hepatic steatosis that occur in obese Zucker rats. The putative
influence of dietary fructans on body weight and fat mass, if confirmed
in humans, would constitute an interesting tool in the control of
obesity. A recent paper reported that in severely obese people (body
mass index >45 kg/m2), 86% were found to have
steatosis (Marceau et al. 1999
). The pathologic
consequences of TAG accumulation in the liver are not well understood,
but more and more studies suggest that fatty liver is more sensitive to
viral infection (hepatitis C), ischemia, or toxic compounds
(Hourigan et al. 1999
, Koneru et al. 1995
). Future studies will be designed to analyze the mechanism
of the "hepatoprotective" effect of dietary fructans in obese
animals to clarify its putative usefulness in the control of the
hepatic alterations linked to obesity in humans.
|
FOOTNOTES |
|---|
2 C. D. is financed by Danone Institute
(Brussels, Belgium).
4 Abbreviations used: ATPCL, adenosine
triphosphate citrate lyase; FAS, fatty acid synthase; ME, malic enzyme;
NIDDM, noninsulin-dependent diabetes mellitus; OFS, oligofructose;
PAP, phosphatidate phosphohydrolase; PL, phospholipids; RT-PCR,
reverse transcriptase-polymerase chain reaction; TAG,
triacylglycerol.
Manuscript received October 1, 1999. Initial review completed November 7, 1999. Revision accepted February 3, 2000.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1.
Agheli N., Kabir M., Berni-Canani S., Petitjean E., Boussairi A., Luo J., Bornet F., Slama G., Rizkalla S. W. Plasma lipids and fatty acid synthase activity are regulated by short-chain fructooligosaccharides in sucrose-fed insulin-resistant rats. J. Nutr. 1998;128:1283-1288
2.
Alles M., de Roos N., Carel Bakx J., van de Lisdonk E., Zock P., Hautvast J. Consumption of oligofructosaccharides does not favorably affect blood glucose and serum lipid concentrations in patients with type 2 diabetes. Am. J. Clin. Nutr. 1999;69:64-69
3. Bacon B., Farahvash M., Janney C., Neuschwander-Tetri B. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994;107:1103-1109[Medline]
4. Boulangé A., Planche E., Gasquet P. Onset and development of hypertriglyceridemia in the Zucker rat (fa/fa). Metabolism 1981;30:1045-1052[Medline]
5. Cheng C., Saggerson E. Rapid antagonistic actions of noradrenaline and insulin on rat adipocyte phosphatidate phospho-hydrolase activity. FEBS Lett 1978;93:120-124[Medline]
6. Delzenne N., Kok N. Effect of non-digestible fermentable carbohydrates on hepatic fatty acid metabolism. Biochem. Soc. Trans. 1998;26:21-23[Medline]
7. Delzenne N., Kok N. Biochemical basis of oligofructose-induced hypolipidemia in animal models. J. Nutr. 1999;129:1467S-1470S
8. Demigné C., Morand C., Levrat A.M., Besson C., Moundras C., Rémésy C. Effects of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes. Br. J. Nutr. 1995;74:209-219[Medline]
9. Demigné C., Rémésy C., Morand C. Short chain fatty acids. Gibson G. R. Roberfroid M. B. eds. Colonic Microbiota, Nutrition and Health 1999:55-69 Kluwer Academic Publishers Dordrecht, The Netherlands.
10. Diehl A. Nonalcoholic steatohepatitis. Semin. Liver Dis. 1999;19:221-229[Medline]
11. Favier M. L., Bost P. E., Guittard C., Demigné C., Rémésy C. The cholesterol-lowering effect of guar gum is not the result of a simple diversion of bile acids toward fecal excretion. Lipids 1997;32:953-959[Medline]
12. Fiordaliso M., Kok N., Desager J. P., Goethals F., Deboyser D., Roberfroid M., Delzenne N. Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats. Lipids 1995;30:163-167[Medline]
13.
Folch J., Lees M., Sloane-Stanley G. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 1957;226:497-509
14. Foreman L. P., Scheemann B. O. Dietary pectin’s effect on starch utilization in rats. J. Nutr. 1982;112:528-533
15. Fukuda N., Azain M. J., Ontko J. A. Altered hepatic metabolism of free fatty acids underlying hypersecretion of very low density lipoproteins in the genetically obese Zucker rats. J. Biol. Chem. 1982;25:571-579
16. Girard J., Ferre P., Foufelle F. Mechanisms by which carbohydrates regulate expression of genes for glycolytic and lipogenic enzymes. Annu. Rev. Nutr. 1997;17:325-352[Medline]
17. Hourigan L. F., Macdonald G. A., Purdie D., Whitehall V. H., Shorthouse C., Clouston A., Powell E. E. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 1999;29:1215-1219[Medline]
18. Hsu R., Lardy H. Malic enzyme. Methods Enzymol 1969;13:230-235
19.
Iritani N., Sugimoto T., Fukuda H., Komiya M., Ikeda H. Oral triacylglycerols regulate plasma glucagon-like peptide-1(7–36) and insulin levels in normal and especially in obese rats. J. Nutr. 1999;129:46-50
20. Jackson K., Taylor G., Clohessy A., Williams C. The effect of the daily intake of inulin on fasting lipid, insulin and glucose concentrations in middle-aged men and women. Br. J. Nutr. 1999;82:23-30[Medline]
21. Jenkins D. J., Vuksan V., Rao A. V., Vidgen E., Kendall C. W., Tariq N., Wursch P., Koellreuter B., Shiwnarain N., Jeffcoat R. Colonic bacterial activity and serum lipid risk factors for cardiovascular disease. Metabolism 1999;48:264-268[Medline]
22. Karpe F. Effects of diet on postprandial lipaemia: a suggestion for methodological standarization. Nutr. Metab. Cardiovasc. Dis. 1997;7:44-55
23.
Kok N., Morgan L., Williams C., Roberfroid M., Thissen J. P., Delzenne N. Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats. J Nutr 1998a;128:1099-1103
24. Kok N., Roberfroid M., Robert A., Delzenne N. Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose in rats. Br. J. Nutr. 1996;76:881-890[Medline]
25. Kok N., Taper H., Delzenne N. Oligofructose modulates lipid metabolism alterations induced by a fat-rich diet in rats. J. Appl. Toxicol. 1998b;18:47-53[Medline]
26. Koneru B., Reddy M., Dela Torre A., Patel D., Ippolito T., Ferrante R. Studies of hepatic warm ischemia in the obese Zucker rat. Transplantation 1995;59:942-946[Medline]
27. Lairon D. Nutritional and metabolic aspects of postprandial lipemia. Reprod. Nutr. Dev. 1996;36:345-355
28. Levrat M. A., Moundras C., Younes H., Morand C., Demigné C., Rémésy C. Effectiveness of resistant starch, compared to guar gum, in depressing plasma cholesterol and enhancing fecal steroid excretion. Lipids 1996;31:1069-1075[Medline]
29.
Levrat-Verny M. A., Behr S., Mustad V., Remesy C., Demigné C. Low levels of viscous hydrocolloids lower plasma cholesterol in rats primarily by impairing cholesterol absorption. J. Nutr. 2000;130:243-248
30.
Lia A., Andersson H., Mekki N., Juhel C., Senft M., Lairon D. Postprandial lipemia in relation to sterol and fat excretion in ileostomy subjects given oat-bran and wheat test meals. Am. J. Clin. Nutr. 1997;66:357-365
31. Linn T. C. Purification and crystallization of rat liver fatty acid synthetase. Arch. Biochem. Biophys. 1981;209:613-619[Medline]
32.
Lowry O., Rosebrough N., Farr A., Randall R. Protein measurements with the Folin phenol reagent. J. Biol. Chem. 1951;193:265-273
33.
Marceau P., Biron S., Hould F. S., Marceau S., Simard S., Thung S. N., Kral J. G. Liver pathology and the metabolic syndrome X in severe obesity. J. Clin. Endocrinol. Metab. 1999;84:1513-1517
34. National Research Council (1985) Guide for the Care and Use of Laboratory Animals. Publication no. 85–23 (rev.). National Institutes of Health, Bethesda, MD.
35. Penicaud L., Ferré P., Terretaz J., Kinebanyan M. F., Leturque A., Doré E., Girard J., Jeanrenaud B., Picon L. Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue. Diabetes 1987;36:626-631
36. Purnell J., Brunzell J. Effect of intensive diabetes therapy on diabetic dyslipidemia. Diabetes Rev 1997;5:434-444
37. Roberfroid M., Delzenne N. Dietary fructans. Annu. Rev. Nutr. 1998;18:117-143[Medline]
38. Takeda Y., Suzuki F., Inoue H. ATP citrate lyase (citrate cleavage enzyme). Methods Enzymol 1969;13:236-238
39. Trautwein E. A., Forgbert K., Rieckhoff D., Erbersdobler H. F. Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters. Biochim. Biophys. Acta 1999;1437:1-12[Medline]
40.
Trautwein E. A., Rieckhoff D., Eerbersdobler H. F. Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters. J. Nutr. 1998;128:1937-1943
41. Younes H., Levrat M. A., Demigné C., Rémésy C. Resistant starch is more effective than cholestyramine as lipid-lowering agent in the rat. Lipids 1995;30:847-853[Medline]
42. Zammitt V. Role of insulin in hepatic fatty acid partitionning: emerging concepts. Biochem. J. 1996;314:1-14
43. Zammitt V., Lankester D. J., Brown A. M., Park B. S. Insulin stimulates triacylglycerol secretion by perfused livers from fed rats but inhibits it in livers from fasted or insulin-deficient rats: implications for the relationschip between hyperinsulinaemia and hypertriglyceridaemia. Eur. J. Biochem. 1999;263:859-864[Medline]
This article has been cited by other articles:
|
|
 |
|
  S. McNear and S. A. Harrison Review: Current status of therapy in nonalcoholic fatty liver disease Therapeutic Advances in Gastroenterology, January 1, 2009; 2(1): 29 - 43. [Abstract] [PDF]
|
|
|
|
 |
|
 F. Respondek, K. S. Swanson, K. R. Belsito, B. M. Vester, A. Wagner, L. Istasse, and M. Diez Short-Chain Fructooligosaccharides Influence Insulin Sensitivity and Gene Expression of Fat Tissue in Obese Dogs J. Nutr., September 1, 2008; 138(9): 1712 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Roberfroid Inulin-Type Fructans: Functional Food Ingredients J. Nutr., November 1, 2007; 137(11): 2493S - 2502S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Delzenne, P. D. Cani, and A. M. Neyrinck Modulation of Glucagon-like Peptide 1 and Energy Metabolism by Inulin and Oligofructose: Experimental Data J. Nutr., November 1, 2007; 137(11): 2547S - 2551S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sugatani, T. Wada, M. Osabe, K. Yamakawa, K. Yoshinari, and M. Miwa Dietary Inulin Alleviates Hepatic Steatosis and Xenobiotics-Induced Liver Injury in Rats Fed a High-Fat and High-Sucrose Diet: Association with the Suppression of Hepatic Cytochrome P450 and Hepatocyte Nuclear Factor 4{alpha} Expression Drug Metab. Dispos., October 1, 2006; 34(10): 1677 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D Cani, C. A Daubioul, B. Reusens, C. Remacle, G. Catillon, and N. M Delzenne Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats J. Endocrinol., June 1, 2005; 185(3): 457 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Neyrinck, H. Alexiou, and N. M. Delzenne Kupffer Cell Activity Is Involved in the Hepatoprotective Effect of Dietary Oligofructose in Rats with Endotoxic Shock J. Nutr., May 1, 2004; 134(5): 1124 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Letexier, F. Diraison, and M. Beylot Addition of inulin to a moderately high-carbohydrate diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans Am. J. Clinical Nutrition, March 1, 2003; 77(3): 559 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Aprikian, J. Busserolles, C. Manach, A. Mazur, C. Morand, M.-J. Davicco, C. Besson, Y. Rayssiguier, C. Remesy, and C. Demigne Lyophilized Apple Counteracts the Development of Hypercholesterolemia, Oxidative Stress, and Renal Dysfunction in Obese Zucker Rats J. Nutr., July 1, 2002; 132(7): 1969 - 1976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Daubioul, N. Rousseau, R. Demeure, B. Gallez, H. Taper, B. Declerck, and N. Delzenne Dietary Fructans, but Not Cellulose, Decrease Triglyceride Accumulation in the Liver of Obese Zucker fa/fa Rats J. Nutr., May 1, 2002; 132(5): 967 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Delzenne, N. Kok, P. Deloyer, and G. Dandrifosse Dietary Fructans Modulate Polyamine Concentration in the Cecum of Rats J. Nutr., October 1, 2000; 130(10): 2456 - 2460. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
