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Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2714
2To whom correspondence should be addressed. E-mail: ferraris{at}umdnj.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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KEY WORDS: • aging and diet • internal organs • intestines and metabolism • mice • nutrient transport
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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60–70% ad libitum (AL) intake not only prolongs the median and
maximum life span in mammals, but also delays the onset of
age-associated degenerative diseases and decreases in physiologic
capacities, including that of the small intestine (Masoro 1992
, Turturro et al. 1999
). ER, the only method
known to date to prolong mammalian life span consistently
(Weindruch 1996
) is a nutritional intervention whose
effects are relatively well known for certain tissues such as liver and
muscle (Kim et al. 1996
) but not for others, especially
the small intestine. This is unfortunate because digestive and
absorptive processes in the small intestine are the first step in the
metabolism of nutrients. The epithelial cells of the small intestine
possess the ability to respond to changing physiologic needs such as
pregnancy and lactation or to pathologic stress such as diabetes
(Ferraris and Diamond 1997
), but the response of the
small intestine to ER remains little known.
The effects on intestinal nutrient transport of a total cessation in
food intake or of changes in luminal concentration of a single nutrient
are well known. For example, intestinal nutrient absorption decreases
dramatically with starvation; the main mechanism underlying this
decrease is a reduction in intestinal mucosal mass (Diamond et al. 1984
). Removal of a nonessential nutrient from the diet,
and therefore from the intestinal lumen of well-fed animals,
decreases the number of intestinal transporters for that nutrient
(Ferraris and Diamond 1986
). ER drastically decreases
the amount of luminal nutrients available for absorption, but its
effect on intestinal function is virtually unknown. Specific activities
of intestinal enzymes were higher in rats that were energy restricted
(Holt et al. 1991
). In aged (24 mo old) mice that had
been energy restricted since 3 mo of age, intestinal transport of
sugars and several amino acids was much higher than that in same age
mice with free access to food, and was comparable to that of young AL
mice (Casirola et al. 1996
, Ferraris et al. 1993b
). In this study, we determined the time course of
intestinal transport adaptations to ER and monitored changes in weights
of internal organs of the mice during ER to determine whether certain
organs are affected by ER more than others. We also determined
adaptations in intestinal uptake by mice starved for 1 and 2 d to
distinguish adaptations to starvation from adaptations to
short-term ER.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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Male mice C57BL/6N were purchased from the National Institute on Aging
(NIA, Bethesda, MD). Mice used in the first series of experiments were
4 mo old, all initially with free unlimited access to food; mice were
delivered in four consecutive batches, each containing at least 22
mice. Mice used in the second series were 13-mo-old mice; half were
mice with unlimited access to food since birth, and the remaining half
were mice that were energy restricted since 16 wk of age. All of the
mice were maintained in individual cages on a 12-h dark:light cycle
(1000–2200 h dark cycle) at 25°C to make their feeding times as
similar as possible. If the light:dark cycle were not reversed, rodents
allowed free access to food would eat most of their food in the dark
(Ferraris et al. 1990
), whereas ER mice would be fed
during normal daytime working hours.
In the first experimental series, the four batches were each divided
randomly into three groups as follows: control mice with unlimited
access to food (AL mice); energy-restricted mice fed 30% (by
weight) less than AL mice (ER mice); and mice starved for 1 or 2 d
(ST mice). All three groups of mice had free access to distilled water
until killed for nutrient uptake or organ weight measurements 1, 2, 10
and 24 d after the start of energy restriction in the case of AL
and ER mice, or 1 and 2 d after the start of starvation in the
case of ST mice. Before the start of energy restriction, the body
weight was stabilized for 7 d after receipt of mice from the NIA.
Series 2 mice were delivered in two batches when they were 12 mo of age; they were used to determine the effect of prolonged ER on intestinal nutrient uptake. Mice in series 2 were purchased from the NIA already energy-restricted. These mice and their AL littermates were shipped overnight to the University of Medicine and Dentistry of New Jersey (UMDNJ) 8 mo after energy restriction, and energy restriction was continued at UMDNJ for an additional 30 d before mice were killed.
All mice (except starved groups) were fed the complete, sterile,
commercially available diets (NIH-31; composition in percentage by
weight; crude protein, 18 analyzed; carbohydrates, 76.5 estimated;
fats, 4.12 analyzed; energy content, 18.2 kJ/kg). The detailed
composition of this diet was described by Eiam-Ong and Sabatini (1999)
. Although the ER group received only 3 g/d of this diet,
they received the same amount of vitamins and minerals as the AL group
because the modified NIH-31 diet for ER mice was supplemented with
essential micronutrients in a proportion that compensated for the
degree of the dietary restriction used. The 3 g/d feeding rate for ER
mice, which is typically 70% of the daily feeding rate of AL mice, is
an accepted procedure at the NIA and defines ER in this study.
Preweighed 3-g pellets provided by the NIA with each shipment were used
in feeding both series 1 and 2 ER mice in the laboratory. The feeding
rate in the AL group of all batches of mice was monitored twice each
week.
Mice were killed 1, 2, 10, 24 (series 1 mice) and 270 d (series 2 mice) after ER began. To minimize the effect of the experimental variation on comparisons, uptake measurements were matched, i.e., one mouse from the AL group, one from the ER group and one from the ST (for d 1 and 2 only) group were killed for each uptake experiment for a total of 6–9 experiments per time point. Moreover, to determine the effect of energy restriction on the weight of internal organs and to minimize the effect of unexpected mortality on uptake experiments, a larger number of mice than that used eventually for uptake experiments were energy restricted or starved. Mice were anesthetized with an overdose of pentobarbital sodium and then killed. The entire small intestine was quickly removed and flushed with ice-cold Ringer’s solution. After being blotted dry with a moist (with saline) paper towel, the small intestine’s length and weight were measured. The most proximal, middle and distal 3-cm segments were used for the preparation of everted sleeves. The other internal organs were subsequently removed, blotted dry and weighed. Mice not used for uptake experiments were also underwent dissection and their internal organs weighed. The methods described in this study were approved by the UMDNJ Institutional Animal Care and Use Committee.
Nutrient uptake measurements.
Glucose, fructose and proline transport rates were determined according
to the method of (Karasov and Diamond 1983
). We chose
these nutrients because their transport rates were greatly affected by
ER (Casirola et al. 1996 and 1997
). The isolated small
intestine was flushed with cold Ringer’s solution (composition in
mmol/L: 128 NaCl, 4.7 KCl, 2.5 CaCl2, 2.2
KH2PO4, 1.2 MgSO4, and 20
NaHCO3; pH 7.3–7.4) bubbled with
95%O2-5%CO2. Each everted sleeve, 1 cm long,
was mounted on a grooved steel rod (3-mm diameter), and preincubated in
Ringer’s solution at 37°C for 5 min. Then they were switched into
the oxygenated solution containing
D-[14C]glucose,
D-[14C]fructose and
L-[3H]proline for 1, 2 and 2 min incubations,
respectively, which are long enough to allow sufficient amounts of
labeled substrates to enter the epithelial cells.
Sleeves incubated in glucose or fructose solutions were rinsed for
20 s in 25 mL ice-cold Ringer’s solution to reduce the
radioactive label in the adherent fluid.
L-[3H]glucose was used to simultaneously
correct for adherent fluid and for passive diffusion of glucose or
fructose (Karasov and Diamond 1983
).
[14C]Polyethylene glycol (molecular weight 4000) was used
to correct for 3H-proline in the adherent fluid. Hence,
both mediated D-sugar uptake and total (mediated plus
diffusive) amino acid transport were measured in this study. All of the
radioisotopes were obtained from Du Pont-NEN (Boston, MA). The
transport rates of D-glucose, D-fructose and
L-proline were determined at 50 mmol/L, a concentration
that yields the Vmax and therefore not
significantly affected by unstirred layers (Karasov and Diamond 1983
).
Uptake results were expressed per milligram of small intestine to
detect specific changes in rates of transport, as well as per
centimeter small intestine to determine changes in total absorptive
capacity for a given nutrient. Uptakes were determined in the proximal,
middle and distal intestinal regions. Uptake per small intestine of a
nutrient was calculated by integrating D-glucose,
D-fructose or L-proline uptake per centimeter
along the length of the small intestine as previously described
(Casirola et al. 1996
).
Statistical analysis.
For organ and body weights, a two-way ANOVA testing for the effects of ER and duration of ER was conducted. The effects of ER and intestinal region on uptake rate were also analyzed by two-way ANOVA. Interactions between diet and duration of ER are mentioned only if significant at P < 0.05. Because duration of starvation was for 1 and 2 d only, a one-way ANOVA was used to test for the effects of ER (for all time intervals) and starvation (d 1 and 2 only) on the following: 1) body weight, organ weight and intestinal uptake capacity at each time interval, and 2) uptakes per milligram and per centimeter at each time interval and intestinal region. When the one-way ANOVA was significant for d 1 and 2, a post-hoc Fisher’s Protected Least Significant Difference test was used to determine which means were significantly different (P < 0.05) from each other (StatView, Cary, NC).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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The mean body weight varied significantly with diet (P
< 0.0001 by two-way ANOVA) and time after ER (P
< 0.0001, Fig. 1
). Interaction between diet and time after ER was also significant
(P < 0.0001). Although initial body weights did not
differ (P = 0.90 by one-way ANOVA), there were
already marked effects of diet 1 (P = 0.014) and 2
(P = 0.004) days after initiation of ER or starvation.
After 1 d, the body weight of starved mice was 11% lower compared
with AL and ER mice. After 2 d, the body weight of starved and ER
mice decreased by 20 and 11%, respectively. By 10, 24 and 270 d
after energy restriction, the body weight of ER mice was 17, 23 and
39% lower, respectively, than that of same age AL mice (P
< 0.01). The difference between AL and ER body weights at
270 d was almost double the difference at 24 d, mainly
because of the large increase in weight of AL mice. The mean feeding
rate for AL mice was 4.3 ± 0.1 g/d; hence, the ER feeding rate of
3 g/d is 70% that of AL mice.
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Organ weights |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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In general, the weights of organs of the gastrointestinal tract were
affected only modestly or not at all by ER (Fig. 2
). By two-way ANOVA, there was no effect of ER (P = 0.68) or duration of ER (P = 0.12) on stomach weight.
There was also no effect of diet on stomach weight after 1
(P = 0.76 by one-way ANOVA) or 2 (P
= 0.79) days. After 270 d, however, the stomach of ER mice
was 25% heavier than that of AL mice (P < 0.05).
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) and duration of ER
(P < 0.01). By 270 d after initiation of ER, the
small intestine weight of AL mice was only 12% greater than that of
ER mice (P < 0.05 by one-way ANOVA), mainly
because small intestine weight in AL mice increased by 15% over the
initial value. As would be expected, total intestine weight decreased
with starvation, particularly 2 d after cessation of food intake
(P < 0.001). This decrease was not due to decreases in
intestinal length but to decreases in average weight per centimeter of
intestine. Intestinal lengths at d 1 were not significantly different
among the three diet groups (P = 0.83): 33.3 ± 3.5, 32.3 ± 3.0 and 31.9 ± 1.9 cm for AL, ER and ST mice,
respectively. On d 2, intestinal lengths also did not differ among
treatment groups (P = 0.19): 30.9 ± 2.1, 30.5 ± 1.8 and 34.8 ± 4.5 cm for AL, ER and ST mice, respectively.
Weight per centimeter did not differ on d 1 (36.0 ± 3.5 for AL,
38.4 ± 3.2 for ER, and 32.9 ± 1.1 mg/cm for ST mice) but
differed markedly (P < 0.01) 2 d after ER (35.9
± 1.9, 37.1 ± 1.4 and 27.8 ± 2.3 mg/cm, respectively)
when the value in ST mice was less than in the other 2 groups.
There was no effect of ER (P = 0.70 by two-way
ANOVA), but there was a modest effect of experimental duration
(P = 0.04) on the weight of the cecum (Fig. 2)
. After
24 d, cecal weight was less in ER than in AL mice (P
= 0.04).
The weight of the large intestine varied with diet (P = 0.03 by two-way ANOVA) and experimental duration (P
< 0.0001). Colon weight in both AL and ER mice increased markedly
with experimental duration (P < 0.0001), although
weights in AL mice were 10% greater than those of ER mice at 10, 24
and 270 d (P = 0.15, 0.04 and 0.16, respectively, Fig. 2
). There was no effect of a 1- or 2-d starvation period on the weight
of the large intestine (P > 0.40).
Other organs.
In general, there were marked differences between AL and ER mice in
weights of organs not located along the gastrointestinal tract
(Fig. 3
). The combined weight of the two kidneys varied with duration
(P = 0.04 by two-way ANOVA) and diet (P
< 0.0001). Within 10 d after ER, there was already an
20% ER-related difference in kidney weight, a difference that
magnified to 35% at 270 d after ER. The interaction between diet
and duration was significant (P = 0.03). The weight of
the kidneys was not affected by starvation of 1 (P = 0.76) or 2 (P = 0.54) days.
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The combined weight of the two lungs varied with diet (P = 0.0006 by two-way ANOVA) and experimental duration (P = 0.008). The difference in weight of the lungs did not become significant until after 24 d of ER when the weight in AL mice was 20% greater than that in ER mice. By 270 d of ER, lung weight was almost 50% greater in AL than in ER mice. The interaction of duration and diet was significant (P = 0.02). There was no effect of starvation on lung weight (P = 0.84 for d 1; P = 0.45 for d 2).
The weight of the heart varied with diet (P < 0.0001 by two-way ANOVA) but not with duration (P = 0.89). There was a significant interaction between diet and duration, however (P = 0.0003), so that the magnitude of ER-related differences in the weight of the heart increased with time, from being similar on d 1 and 2 after ER, to 16% by d 10, to 36% by d 24 and eventually to 57% by d 270. There was an effect of starvation by d 2 (P = 0.02).
Two organs associated with the gastrointestinal system but not located
along the gastrointestinal tract were markedly affected by ER (Fig. 3)
.
The weight of the pancreas varied with duration (P = 0.0003 by two-way ANOVA) and ER (P < 0.0001). From
d 10 to 270, the pancreas weight was 30% less in ER than in AL mice.
The interaction between experimental duration and diet was significant
(P = 0.0008). Starvation markedly reduced the weight of
the pancreas (P < 0.001).
Liver weight varied with both diet (P < 0.0001 by two-way ANOVA) and duration (P < 0.0001). The liver weight increased with experimental duration in AL mice but decreased with duration in ER mice, so that after 10 mo of ER, liver weights in AL mice were more than twice those of ER mice. Starvation periods of 1 and 2 d resulted in marked reductions in liver weight (P < 0.001).
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Nutrient uptake |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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After 2 d, there was a significant effect of dietary treatment on
glucose, fructose and proline uptake per centimeter (P
< 0.001 by two-way ANOVA, Fig. 4
). For fructose uptake per centimeter, there was an interaction between
diet and intestinal region (P = 0.04). Most of the
decrease occurred in the proximal and middle intestinal regions of
starved mice (P < 0.05 by one-way ANOVA). Unlike
uptake per centimeter, glucose (P = 0.09, by
two-way ANOVA), fructose (P = 0.47) and proline
(P = 0.67) uptake per milligram was independent of dietary
treatment, indicating that the effect of starvation was mainly on the
amount of intestinal tissue per centimeter, as previously described.
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). However, fructose uptake per milligram and per centimeter
(P < 0.01, by two-way ANOVA, Fig. 5
) increased
significantly with ER because fructose uptake almost doubled in the
proximal small intestine.
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) tended to increase with ER. Fructose uptake per milligram and per
centimeter was also greater (P < 0.001 by two-way
ANOVA) in ER mice. Fructose uptake was greater in ER than in AL mice in
all intestinal regions. Proline uptake per milligram and per centimeter
also varied significantly with diet (P < 0.0001).
Proline uptake in ER mice was greater than that in control mice in the
middle and distal intestinal regions.
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Two days after initiation of starvation, total intestinal glucose
(P = 0.02 by one-way ANOVA), fructose (P
= 0.001) and proline (P = 0.0003) uptake capacity
each decreased dramatically in starved mice (Fig. 7
). Intestinal absorptive capacity for glucose, fructose and proline did
not change with an ER duration of 1, 2 and 10 d. Intestinal
fructose, but not glucose or proline, uptake capacity increased
markedly with ER for 24 d (P = 0.01). However,
after 270 d of ER, intestinal glucose (P = 0.04),
proline (P = 0.0001) and fructose (P = 0.004) uptake capacities increased markedly.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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Although ER leads to modest decreases in body weight and prevents
age-related increases in body weight induced by AL consumption,
there has been no report on how weights of internal organs are
affected. Rat epididymal and retroperitoneal fat pads decreased
modestly (10%) in weight with a brief ER lasting for 20 d, but
decreased markedly (80%) with chronic ER lasting for 15 mo
(Dean and Cartee 1996
). Our results indicate that in
mice, weights of internal organs not along the gastrointestinal tract
decreased with ER. The time course of the diet-related change in
weight also varied among these organs. In the kidneys, spleen, lungs
and heart, the diet-related difference in weight was observed after
10 d of ER, when body weight of ER mice became significantly less
than that of AL mice. Acute starvation for 1–2 d had no effect on the
weight of these organs. In contrast, weight loss in the pancreas and
liver occurred quite rapidly and seemed directly related to the amount
of food being processed, so that weight loss was moderate with acute
(1–2 d) ER, but severe with starvation. After 2 d of starvation,
decreases in combined weights of the stomach, liver and small
intestine, although significant, constituted only a small fraction
(10%) of the loss in body weight. In passerine birds, starvation
also markedly decreased weights of these organs, but the lost weight
constituted a larger fraction of the loss in body weight
(Karasov and Pinshow 1998
).
It is not clear why the gastrointestinal tract was "spared" during
ER. In fact, chronic ER even led to larger stomachs. Starvation
decreased intestinal mass in parallel with a decrease in body weight,
whereas chronic ER led to decreases in body weight with relatively
modest effects on intestinal structure. There was no (Casirola et al. 1997
) or little (Casirola et al. 1996
)
ER-induced decrease in villous height, mucosal mass or intestinal
mass. The number of cells on the villous columns was similar in AL and
ER mice (Koga and Kimura 1978
), although the number of
proliferative cells and the rate of cell proliferation decreased
(Koga and Kimura 1980
, Lok et al. 1988
).
The ER-induced decrease in proliferation rate led to decreases in
enterocyte migration rate and enterocyte life span; consequently, cells
stayed on the villus for a longer time. It is possible that energy
restriction reduced cell turnover throughout the gastrointestinal tract
without affecting its gross anatomy.
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Intestinal transport adaptation to energy restriction is a gradual process |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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suggest that the effect of ER develops gradually over
time. The difference between absorption rates in ER and AL mice is due
mainly to increases associated with prolonged ER rather than to
decreases associated with prolonged AL consumption and aging. ER has no
effect on intestinal anatomy and weight; hence, its effect on nutrient
uptake expressed per milligram of tissue or per centimeter of intestine
is the same. In contrast, the effect of acute starvation is mainly a
rapid decrease in transport per centimeter of gut, with little effect
on transport per milligram.
The effects of ER may be better compared with those of semistarvation
or malnutrition rather than those of total starvation because the
former conditions allow for partial feeding (Ferraris and Carey 2000
). Under the conditions of semistarvation or malnutrition,
glucose transport per milligram in brush border membrane vesicles
increased approximately twofold over that in well-fed rabbits and
rats (Brot-Laroche et al. 1988
, Butzner et al. 1990
, Gupta and Waheed 1992
, Marciani et al. 1987
). However, the time course of the effects of
semistarvation and malnutrition was generally rapid, occurring over
hours and days instead of months and years as is the case for ER.
Age may be a potential factor in intestinal adaptations to ER. In
young, (3 mo old) mice (this study), 24 d of ER resulted in
increases in fructose transport. In contrast, in aged (24 mo old) mice,
30 d of ER had no effect on the transport of fructose or that of
any other nutrient (Casirola et al. 1996
). Age has also
been shown to impair the ability of the gut to alter absorption rates
in response to drastic changes in composition of the diet
(Ferraris and Vinnakota 1993
). When ER aged mice are
switched to AL consumption for 1 mo, intestinal nutrient transport
decreases dramatically (Casirola et al. 1997
). Hence, a
short duration of AL consumption abolishes the effects of lifelong ER
on intestinal nutrient transport by aged mice.
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Intestinal uptake capacity and metabolic mass |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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 | (1) |
where IW represents intestinal weight. This equation apportions
the change in intestinal absorptive capacity normalized to metabolic
body weight
(
J/BW0.75) to either
of two major mechanisms, i.e., a change in amount of intestine relative
to body weight (IW/BW0.75) or to a
change in the ability of intestine to absorb nutrients
(J/IW). A detailed derivation and a discussion of the
subdivisions of each major mechanism can be found in Ferraris and Diamond (1997)
. After 270 d of ER, intestinal uptake
capacity normalized to metabolic weight
(J/BW0.75) for glucose, fructose or
proline was 75–120% greater in ER than that in AL mice (Table 1
). Similar results were obtained in mice that were energy-restricted
for 20 mo (Casirola et al. 1996
). This suggests that
chronic ER leads to intestinal adaptations that allow more nutrients to
be absorbed per unit metabolic body weight.
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Because ER has modest effects on the factor
(IW/BW0.75), the changes in uptake
capacity/g0.75 must be due to changes in the
so-called physiologic factor (J/IW), which increased
by 35% (for glucose) or 75% (fructose or proline) after 270 d of
ER. This means that more nutrients are absorbed by ER mice by the same
amount of intestinal tissue, as previously observed in mice that were
energy restricted for 20 mo (Casirola et al. 1997
).
These physiologic and anatomical contributions to intestinal adaptation
vary depending on the factor inducing the adaptation. In obese mice
whose metabolic body weights are 56% greater than those of lean
littermates, there is a 55% increase in
IW/BW0.75 but no change in J/IW, a
pattern opposite that of ER mice. Thus, in obese mice, an increase in
nutrient absorptive capacity is due solely to increases in intestinal
mass. In streptozotocin-diabetic mice, whose metabolic body weights
are similar to those of control littermates, both factors increase
markedly (Ferraris et al. 1993a
, Ferraris and Vinnakota 1995
), explaining the large increase in nutrient
absorptive capacity. In young adult rats, whose intestines were
resected by up to 80% 1 wk before killing, there were marked increases
in the weight of the remnant small intestine and a reduction in
transport activity per unit intestinal weight; hence, intestinal uptake
capacity was markedly lower than preresection values (O’Connor et al. 1999
).
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Proximate mechanisms of adaptation |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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J/IW)
for a certain nutrient are the number of transporters per cell, the
ratio of absorptive to nonabsorptive cells, the turnover number (number
of moles of substrate transporter per mole of transporter) of each
transport site and the affinity constant of transporter for its
substrate (Ferraris and Diamond 1997
). The mechanism
underlying the increased transport rate during chronic ER may be an
increase in the ratio of absorptive to nonabsorptive cells because of
decreases in enterocyte migration rate during ER (Lok et al. 1988
). In rats subjected to ER, the increase in brush border
sucrase activity was due to this same mechanism (Koga and Kimura 1978
). In starved or protein-malnourished rats, the ratio
of the density of valine transporting sites to nontransporting sites
also increased (Syme and Smith 1982
, Thompson and Debnam 1986
). Clearly, this hypothesis requires further
investigation.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: AL, (ad libitum) consumption to satiety; BW, body weight; ER, 70% energy-restricted; IW, intestinal weight; NIA, National Institute on Aging; ST, starved; UMDNJ, University of Medicine and Dentistry of New Jersey.
Manuscript received April 19, 2000. Initial review completed May 26, 2000. Revision accepted December 6, 2000.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSOrgan weightsNutrient uptakeDISCUSSIONIntestinal transport adaptation...Intestinal uptake capacity and...Proximate mechanisms of...REFERENCES |
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1.
Brot-Laroche E., Dao M. T., Alcalde A. I., Delhomme B., Triadou N., Alvarado F. Independent modulation by food supply of two distinct sodium-activated D-glucose transport systems in the guinea pig jejunal brush-border membrane. Proc. Natl. Acad. Sci. U.S.A. 1988;85:6370-6373
2.
Butzner J. D., Brockway P. D., Meddings J. B. Effects of malnutrition on microvillus membrane glucose transport and physical properties. Am. J. Physiol. 1990;259:G940-G946
3. Casirola D. M., Lan Y., Ferraris R. P. Effects of changes in calorie intake on intestinal nutrient uptake and transporter mRNA levels in aged mice. J. Gerontol. A Biol. Sci. Med. Sci. 1997;52:B300-B310[Abstract]
4.
Casirola D. M., Rifkin B., Tsai W., Ferraris R. P. Adaptations of intestinal nutrient transport to chronic caloric restriction in mice. Am. J. Physiol. 1996;271:G192-G200
5. Dean D. J., Cartee G. D. Brief dietary restriction increases skeletal muscle glucose transport in old Fischer 344 rats. J. Gerontol. A Biol. Sci. Med. Sci. 1996;51:B208-B213[Abstract]
6.
Diamond J. M., Karasov W. H., Cary C., Enders D., Yung R. Effect of dietary carbohydrate on monosaccharide uptake by mouse small intestine in vitro. J. Physiol. (Lond.) 1984;349:419-440
7.
Eiam-Ong S., Sabatini S. Food restriction beneficially affects renal transport and cortical membrane lipid content in rats. J. Nutr. 1999;129:1682-1687
8. Ferraris R. P., Carey H. V. Intestinal transport during fasting and malnutrition. Annu. Rev. Nutr. 2000;20:195-219[Medline]
9. Ferraris R. P., Casirola D. M., Vinnakota R. R. Dietary carbohydrate enhances intestinal sugar transport in diabetic mice. Diabetes 1993a;42:1579-1587[Abstract]
10. Ferraris R. P., Diamond J. M. Use of phlorizin binding to demonstrate induction of intestinal glucose transporters. J. Membr. Biol. 1986;94:77-82[Medline]
11.
Ferraris R. P., Diamond J. Regulation of intestinal sugar transport. Physiol. Rev. 1997;77:257-302
12.
Ferraris R. P., Hsiao J., Hernandez R., Hirayama B. Site density of mouse intestinal glucose transporters declines with age. Am. J. Physiol. 1993b;264:G285-G293
13. Ferraris R. P., Vinnakota R. R. Regulation of intestinal nutrient transport is impaired in aged mice. J. Nutr. 1993;123:502-511
14.
Ferraris R. P., Vinnakota R. R. Intestinal nutrient transport in genetically obese mice. Am. J. Clin. Nutr. 1995;62:540-546
15.
Ferraris R. P., Yasharpour S., Lloyd K. C., Mirzayan R., Diamond J. M. Luminal glucose concentrations in the gut under normal conditions. Am. J. Physiol. 1990;259:G822-G837
16. Gupta P. D., Waheed A. A. Effect of starvation on glucose transport and membrane fluidity in rat intestinal epithelial cells. FEBS Lett 1992;300:263-267[Medline]
17. Holt P. R., Heller T. D., Richardson A. G. Food restriction retards age-related biochemical changes in rat small intestine. J. Gerontol. 1991;46:B89-B94[Medline]
18. Karasov W. H., Diamond J. M. A simple method for measuring intestinal solute uptake in vitro. J. Comp. Physiol. 1983;152:105-116
19. Karasov W. H., Pinshow B. Changes in lean mass and in organs of nutrient assimilation in a long-distance passerine migrant at a springtime stopover site. Physiol. Zool. 1998;71:435-448[Medline]
20. Kim J. D., Yu B. P., McCarter R. J., Lee S. Y., Herlihy J. T. Exercise and diet modulate cardiac lipid peroxidation and antioxidant defenses. Free Radic. Biol. Med. 1996;20:83-88[Medline]
21. Koga A., Kimura S. Influence of restricted diet on epithelial renewal and maturation in the mice jejunum. J. Nutr. Sci. Vitaminol. 1978;24:323-329
22. Koga A., Kimura S. Influence of restricted diet on the cell cycle in the crypt of mouse small intestine. J. Nutr. Sci. Vitaminol. 1980;26:33-38
23. Lok E., Nera E. A., Iverson F., Scott F., So Y., Clayson D. B. Dietary restriction, cell proliferation and carcinogenesis: a preliminary study. Cancer Lett 1988;38:249-255[Medline]
24. Marciani P., Lindi C., Faelli A., Esposito G. Effects of semistarvation on transintestinal D-glucose transport and D-glucose uptake in brush border and basolateral membranes of rat enterocytes. Pflugers Arch 1987;408:220-223[Medline]
25.
Masoro E. J. Retardation of aging processes by food restriction: an experimental tool. Am. J. Clin. Nutr. 1992;55:1250S-1252S
26.
O’Connor T. P., Lam M. M., Diamond J. Magnitude of functional adaptation after intestinal resection. Am. J. Physiol. 1999;276:R1265-R1275
27. Syme G., Smith M. W. Intestinal adaptation of protein deficiency. Cell Biol. Int. Rep. 1982;6:573-578[Medline]
28. Thompson C. S., Debnam E. S. Hyperglucagonaemia: effects on active nutrient uptake by the rat jejunum. J. Endocrinol. 1986;111:37-42[Abstract]
29. Turturro A., Witt W. W., Lewis S., Hass B. S., Lipman R. D., Hart R. W. Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program [In Process Citation]. J. Gerontol. A Biol. Sci. Med. Sci. 1999;54:B492-B501[Abstract]
30. Weindruch R. Caloric restriction and aging. Sci. Am. 1996;274:46-52[Medline]
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