Vol. 279, Issue 1, R230-R238, July 2000
Attenuation of circadian rhythms of food intake and
respiration in aging diabetes-prone BHE/Cdb rats
Clayton E.
Mathews,
Kathie
Wickwire,
Wiliam P.
Flatt, and
Carolyn D.
Berdanier
Department of Foods and Nutrition, University of Georgia, Athens,
Georgia 30602
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ABSTRACT |
The hypothesis that BHE/Cdb
rats with mutations in their mitochondrial genome might accommodate
this mutation by changing their food intake patterns was tested. Four
experiments were conducted. Experiments 1 and 2 examined food intake patterns of BHE/Cdb rats fed a stock diet or
BHE/Cdb and Sprague-Dawley rats fed a high-fat diet from weaning.
Experiment 3 examined the daily rhythms of respiration and
heat production in these rats at 200 days of age. Experiment
4 examined the effects of diet composition on these measurements
at 50-day intervals. The Sprague-Dawley rats, regardless of diet, had
the typical day-night rhythms of feeding and respiration. In contrast,
the BHE/Cdb rats fed the high-fat diet showed normal rhythms initially,
but with age, these rhythms were attenuated. The changes in rhythms
preceded the development of glucose intolerance.
heat production; mitochondrial diabetes; high-fat diet
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INTRODUCTION |
OVER THE
LAST 30 years we have studied the metabolic characteristics of
the BHE/Cdb rat (3-9, 12,
13, 15-25). At first, these rats were
quite heterogeneous, but through selective breeding, we developed a
strain of rats that is quite uniform in its metabolic characteristics.
Selection pressure was applied to the avoidance of obesity and the
development of abnormal glucose tolerance at 300 days of age.
Throughout this breeding program, we periodically determined their
hyperlipogenic and glycemic characteristics, and these characteristics
were never lost. The strain is now in its 86th generation as a closed
colony. The BHE/Cdb rat typically has a twofold increase in de novo
hepatic lipogenesis and a 40% increase in gluconeogenesis. These
characteristics were first reported by Lakshmanan et al.
(20) and Berdanier (5), respectively. These
two features were responsive to dietary manipulation, in that high
sugar feeding and/or the use of saturated fat, instead of corn oil,
increased their activity. Mitochondrial activity was also observed to
differ from that of a control strain, and it too was responsive to
dietary manipulation (8, 9, 12, 13, 16, 25). The impaired
glucose tolerance is age related. That is, as the animals age, glucose
intolerance develops (4, 6, 7).
This glucose intolerance is maternally inherited (21,
24) and diet responsive (4, 6,
7). In male animals fed an unrefined cereal-based diet,
impaired glucose tolerance appears at 300 days of age. In rats fed
sugar-rich and/or fat-rich diets, this impaired glucose tolerance
appears much earlier. In some instances, it appears as early as 100 days of age (4, 6, 7). Despite
all these metabolic differences due to strain and diet, the total daily
food intake is very similar to that of control animals. Animals of the
BHE/Cdb strain are not hyperphagic.
The rats of the BHE/Cdb strain have been found to have two homoplasmic
mutations in the mitochondrial ATPase 6 gene as well as three
heteroplasmic mutations in this same gene (23; C. Herrnsted, personal
communication). These mutations have been found in all tissues tested
(22). The genotype and the phenotype are maternally inherited (21, 22). As a result of these
mutations, mitochondria isolated from these animals have been found to
be slightly inefficient (8). This inefficiency is
negatively correlated with its characteristically increased hepatic de
novo lipogenic activity (12) and is also maternally
inherited (21). The question that arises from these reports is how these animals manage to survive and reproduce. What
accommodations do they make to continue life? BHE/Cdb rats are
relatively short lived compared with Sprague-Dawley and Wistar rats.
Their average life span is <600 days, whereas the life span of control
rats is roughly double this.
The present report addresses the issue of how these animals accommodate
their genetic mitochondrial mutation. We previously reported that, in
part, their accommodation involves a difference in their choice of
metabolic fuels (9, 16, 17). The
present work monitored BHE/Cdb and Sprague-Dawley rats with respect to the circadian rhythms of respiration and food intake patterns as the
animals aged. We hypothesized that, in part, the accommodation to their
inherent mitochondrial defect could involve a shift in feeding
behavior. To test this hypothesis, we conducted several experiments.
Experiment 1 examined the daily feeding behavior of BHE/Cdb
rats fed an unrefined cereal-based diet. Experiments 2 and
3 compared BHE/Cdb and Sprague-Dawley rats fed a high-fat diet until 200 days of age. In experiment 4, we studied rats
at 50-day intervals from weaning until 250 days of age by measuring whole body respiration and studying feeding behavior. We found that
young rats of both strains fed the stock diet or the low-fat purified
diet had the usual day-night feeding behavior and respiratory patterns.
As the BHE/Cdb rats aged, their feeding patterns shifted. In
particular, the BHE/Cdb rats fed the high-fat diet shifted their
feeding patterns and respiratory activity as they aged, such that the
day-night pattern at 50 days of age was abolished by the time they were
killed at 250 days of age.
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METHODS AND MATERIALS |
Animals and diets.
Male weanling BHE/Cdb (University of Georgia colony) and Sprague-Dawley
(Harlan Sprague Dawley, Indianapolis, IN) rats were used.1 In experiments
1-3, group size was six. In experiment 4, group size was 12. The rats were offered an unrefined cereal-based diet (Diet
5012, PMI Feeds, St. Louis, MO), a 48% sucrose-18.5% corn oil diet,
or a 65% sucrose-5% corn oil diet (Table
1). These diets are designated the stock
diet, the high-fat diet, and the low-fat diet. The low-fat diet had the
same percent distribution of carbohydrate, fat, and protein as the
stock diet.
The animals were housed individually in hanging wire mesh cages in a
room regulated for light (lights on 0600-1800), temperature (21 ± 1°C), and relative humidity (40-50%). Animal care
followed the recommendations set forth in the Guide for the Care
and Use of Laboratory Animals [DHHS Publ. (NIH) 85-23, 1985].
The animal care facility is under the supervision of a licensed
veterinarian. Specific pathogen-free conditions were maintained and
ensured through the monthly monitoring of sentinel animals for the
presence of common pathogens. Food and water were always available,
except as noted below. The food was stored at 4°C until provided to
the animals. Except when the animals were in the respiration chambers, food intakes and body weights were measured weekly. Food intake was
expressed as grams of food consumed per 100 g body wt. This adjustment allowed for the comparison of food consumed among animals of
different body weights.
Indirect calorimetry.
Animals were placed in individual open-circuit respiration chambers at
200 days of age (experiment 3) or at 50, 100, 150, 200, and
250 days of age (experiment 4). The gas exchange was measured at 16.5-min intervals over a 48-h period. The carbon dioxide
concentration was measured using an infrared analyzer, the oxygen
concentration was determined using an Oxymax oxygen sensor battery
(Columbus Instrument, Columbus, OH), and the results of these analyses
were used to calculate heat production as well as the respiratory
quotient (RQ). Airflow was measured and regulated by a mass flow
controller. Water consumption (licks/min) and feeding activity were
also recorded automatically.
Other measurements.
In experiment 4, fasting (16 h without food) and nonfasting
blood glucose (glucose oxidase, kit 510, Sigma Chemical, St. Louis, MO)
and free glycerol and triglycerides (kit 360, Sigma Chemical) were
determined. The fasting determinations were performed in the morning
(8-9 AM), and the nonfasting measurements were made at 2 PM. This
time was selected to coincide with the maximum difference in indirect
calorimetry between the strains at the time of measurement. Glucose
tolerance was determined after an overnight fast (14-16 h without
food) at 50, 200, and 250 days of age in experiment 4.
Glucose tolerance testing consisted of measuring the blood glucose
level before and at 30, 60, and 120 min after a glucose challenge of 1 g/100 g body wt administered per os as a 25% solution.
Statistical analysis.
Statistical significance was determined using Super ANOVA for the
Macintosh (Abacus Systems, Berkeley, CA). Experiments 1 and
2 were 1 × 4 experiments and were analyzed
statistically using a one-way ANOVA. Experiment 3 utilized
regression analysis, and experiment 4 was analyzed using
ANOVA for this 2 × 3 × 5 experiment. The ANOVA on
experiments 1-3 was followed by Fisher's
least-significant difference test to determine P values. The
ANOVA used for experiment 4 was followed by Duncan's new
multiple-range test to identify significantly different means. Age, as
a variable in these experiments, was not evaluated separately.
P < 0.05 was considered significant.
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RESULTS |
Food intake.
Table 2 shows the food intake adjusted
for body weight of BHE/Cdb rats fed the stock diet from 40 to 190 days
of age (experiment 1). With age, there was a progressive
change in food consumed that is accounted for by the changing needs of
the animal with maturation. There was a change in feeding pattern as
well. In these rats, there were shifts in feeding, such that the usual day-night pattern was suppressed as the animals matured. At 40 days of
age, the rats consumed 67% of their food during the dark phase of the
lighting cycle. By 140 days of age, the rats consumed 56% of their
food during the dark phase, and by 200 days of age, this had fallen to
49% of their total food intake. Table 2 provides the results of the
ANOVA of these data. Age and time period had significant effects on
food intake.
In experiment 2, we compared BHE/Cdb and Sprague-Dawley rats
fed a 48% sucrose-18% corn oil diet from weaning until 190 days of
age (Fig. 1). As in experiment
1, we observed the usual day-night food intake pattern that
characterizes a nocturnal animal such as the young rat. However, the
strains differed with age in their feeding patterns. Just as we noted a
steady shift toward light phase feeding in the BHE/Cdb rats fed the
stock diet in experiment 1, this shift also occurred in
these rats when fed the high-sugar-high-fat diet. In contrast, the
Sprague-Dawley rats did not show as marked a shift. Yes, there was an
age-related change in feeding (the animals ate progressively less per
100 g body wt as they aged), but the Sprague-Dawley rats continued
to consume the majority of their food during the dark phase of the
lighting cycle, whereas the BHE/Cdb rats did not. These differences due
to age and strain in light phase feeding were significant.
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Fig. 1.
Relative 12- and 24-h food intakes of BHE/Cdb (BHE) and
Sprague-Dawley (SD) rats fed an 18.5% corn oil diet from weaning until
190 days of age. Values are means ± SE; n = 6. * Significant (P < 0.05) differences in light phase
feeding. A Significant (P < 0.05) age
effects within strain.
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Because we wanted to confirm these strain differences in feeding
behavior, we repeated these feeding measurements with animals of both
strains fed the stock diet, the high-fat diet, or the low-fat diet
(experiment 4). In this experiment, we observed the feeding
patterns at 50-day intervals from weaning to 250 days of age. Thus our
period of observation was longer than that used in the earlier
experiments. Furthermore, we expanded the experiment so that we could
make simultaneous measurements of rats fed one of three diets. The
stock and the high-fat diets were the same as those used in
experiments 1-3, and we added a third diet, a low-fat
diet, which replicated the proximate composition of the stock diet but
used the same ingredients used in the high-fat diet. This repeat of the
earlier experiments was made possible through the expansion of the
indirect calorimetry facility.
Figure 2 shows the food intake patterns
of both strains of rats fed these three diets as they aged from 50 to
250 days of age. The intervening ages are not shown to save space. The
results of the ANOVA of these data are shown in Table
3. There were significant strain, diet,
and interacting effects on daily food intake as the animals aged from
50 to 250 days of age.
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Fig. 2.
Age changes in the relative food intake during the light
(open portions of bars) and dark (filled portions of bars) phases of
the 12:12-h light-dark cycle of BHE/Cdb and Sprague-Dawley rats fed a
high-fat, low-fat, or stock diet; n = 12. See Fig. 1
legend for explanation of symbols. A: 50 days of age;
B: 250 days of age.
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Table 3.
ANOVA of the food intake of BHE/Cdb and Sprague-Dawley rats fed
stock, low-fat, or high-fat diet from weaning to 250 days of age
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These results confirm those found in experiments 1 and
2, in that we observed a shift in the day-night feeding
patterns of the BHE/Cdb rats, whereas the Sprague-Dawley rats retained
their nocturnal feeding pattern. Age and diet affected the feeding
pattern, such that the BHE/Cdb rats shifted to more daytime feeding
when given the high-fat diet at an earlier age than the rats fed the stock diet. Rats fed the low-fat diet shifted at an earlier age than
those fed the stock diet but not as early as those fed the high-fat diet.
Indirect calorimetry.
Figures 3 and
4 show the light-dark variation in RQ of
the BHE/Cdb and Sprague-Dawley rats (experiment 3). In Fig.
3, a time-dependent change in RQ was observed in rats fed the stock
diet. These rats were 200 days of age at the time of observation.
Although strain differences in RQ were observed, the differences were
not as marked as those shown in Fig. 4. These rats also were 200 days
of age, but instead of the stock diet, they were fed the high-fat diet. The Sprague-Dawley rats had high RQs during the dark phase of the
lighting cycle and low RQs during the light phase. Differences in RQs
were smaller throughout the 24-h light-dark cycle in the BHE/Cdb rats.
The RQs of the BHE/Cdb rats were higher during the light phase and
lower during the dark phase than those of the Sprague-Dawley rats. The
times at which there were significant strain differences are noted on
Figs. 3 and 4. The 24-h RQ patterns for the 50- and 250-day-old rats
fed the stock diet, the low-fat diet, or the high-fat diet
(experiment 4) are shown in Figs.
5 and 6.
Consistent with the results shown for experiment 3, there was a diet- and strain-dependent shift in RQ rhythm. The high-fat diet
strain difference is particularly noticeable.
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Fig. 3.
Circadian rhythm of the respiratory quotients (RQ) of
200-day-old BHE/Cdb and Sprague-Dawley rats fed a stock diet;
n = 6. * Significant (P < 0.05)
differences at specific time points.
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Fig. 4.
Circadian rhythm of the RQ of 200-day-old BHE/Cdb and
Sprague-Dawley rats fed a high-fat diet; n = 6. * Significant (P < 0.05) differences at specific
time points.
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Fig. 5.
Circadian rhythms of the RQ of 50-day-old BHE/Cdb ( )
and Sprague-Dawley ( ) rats fed a stock diet (A), a
low-fat diet (B), or a high-fat diet (C).
* Significant (P < 0.05) strain differences at
specific time points; n = 12.
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Fig. 6.
Circadian rhythms of the RQ of 250-day-old BHE/Cdb ()
and Sprague-Dawley () rats fed a stock diet (A), a
low-fat diet (B), or a high-fat diet (C).
* Significant (P < 0.05) strain differences within
each diet comparison at specific time points; n = 12.
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Table 4 gives the values for gross heat
production (kJ/24 h) and heat production adjusted for metabolic body
size (kJ/kg0.75) in the animals at 50 and 250 days of age.
Although we made these measurements at 50-day intervals, the
intervening observations are not reported to save space. Although no
differences in heat production were observed in the 50-day-old rats, by
250 days of age, strain and diet differences were found. The
250-day-old Sprague-Dawley rats fed the low-fat diet produced less heat
than their Sprague-Dawley cohorts fed the high-fat or the stock diet.
In contrast, the BHE/Cdb rats at this age produced more heat when fed
the high-fat diet than when fed either of the other two diets. ANOVA of
these data revealed significant diet, strain, and diet-strain
interaction effects. When heat production was adjusted for metabolic
body size, again there were no significant differences at 50 days of age. At 250 days of age, the Sprague-Dawley rats fed the high-fat or
low-fat diet produced less heat than their stock diet-fed cohorts and
than the BHE/Cdb rats fed any of the diets. ANOVA of these data
revealed significant diet, strain, and diet-strain interaction effects.
Other measurements.
Consistent with previous reports (3, 4,
10), strain and diet differences were observed in the
triglyceride and free glycerol levels in the fasting and nonfasting
blood (Figs. 7 and 8). In the fasting state, BHE/Cdb rats
had higher levels of triglycerides and glycerol than the Sprague-Dawley
rats, and these differences were diet and age dependent (Table
5). As the BHE/Cdb rats aged from 50 to
250 days of age, their blood triglycerides and free glycerol levels
rose, whereas these measures in the Sprague-Dawley rats were unchanged
as the animals aged. Feeding the purified diets to the BHE/Cdb rats
resulted in increases in triglycerides and glycerol, whereas these
diets had little effect on these measures in the Sprague-Dawley rats.
The strain differences in serum triglycerides and glycerol were more
pronounced in the nonfasted rats (Fig. 8), and this was probably due to
the differences in feeding patterns between the strains. The BHE/Cdb
rats had far higher nonfasting values, probably because they were
eating substantially more during the light phase than were the
Sprague-Dawley rats. ANOVA of the triglyceride and glycerol data showed
that diet and strain had significant effects on these measurements
(Table 5).
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Fig. 7.
Fasting triglyceride (A) and glycerol
(B) levels in 50- and 250-day-old BHE/Cdb and Sprague-Dawley
rats fed a stock diet, a low-fat diet, or high-fat diet from weaning
until 250 days of age; n = 12.
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Fig. 8.
Nonfasting triglyceride (A) and glycerol
(B) levels in BHE/Cdb and Sprague-Dawley rats fed a stock
diet, a low-fat diet, or a high-fat diet from weaning until 250 days of
age; n = 12.
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Table 5.
ANOVA for serum triglycerides, glycerol, fasting glucose, and area
under the curve for glucose tolerance
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Glucose tolerance, measured at 50 and 250 days of age, was affected by
age and strain (Fig. 9). Figure
9A shows that at 50 days of age all the rats returned to
their prechallenge blood glucose level. There were no strain or diet
differences. However, by 250 days of age (Fig. 9B), rats of
the BHE/Cdb strain, regardless of diet, failed to return to their
prechallenge blood glucose levels, whereas rats of the Sprague-Dawley
strain, except those fed the high-fat diet, did. The Sprague-Dawley
rats fed the high-fat diet did not have as high a 30-min postchallenge
glucose level as the BHE/Cdb rats fed the same diet, yet the strains
did not differ at 120 min. ANOVA of the fasting blood glucose and the area under the curve showed significant diet, strain, and diet-strain interaction effects at 250 days of age (Table 5). A diet-strain interaction effect on fasting blood glucose was found at 50 days of
age, but no other effects were observed at this age.
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Fig. 9.
Glucose tolerance of 50-(A) and 250-day-old
(B) BHE/Cdb and Sprague-Dawley rats fed a stock diet, a
low-fat diet, or a high-fat diet from weaning to 250 days of age;
n = 12.
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DISCUSSION |
The results of the present work raise some important questions
about the nature of the cues that influence (or fail to influence) metabolism. Examination of the data from the Sprague-Dawley rats gives
clear indication that the lighting regimen cues feeding and that this
feeding influences intermediary metabolism as assessed by indirect
calorimetry. The food intake during the dark phase of the lighting
cycle cues the oxidation of carbohydrate, which, in turn, is reflected
by the elevations in RQ in the periods that follow. The stock diet is
rich in complex carbohydrates from cereal grains, and this carbohydrate
has a longer residence time in the intestinal tract than the low-fat
diet, which has the same proximate composition but contains sugar as
the carbohydrate source. This carbohydrate is readily absorbed and
thus, when used as the metabolic fuel, will result in an RQ close to 1. When the diet is richer in fat (with smaller amounts of sugar), this
too cues the RQ, but the excursions are broader than when the stock
diet is consumed. This too is probably due to the nature of the diet
consumed. This diet has a combination of sugar (as the carbohydrate
source) and corn oil as the fat source. The sugar will disappear
relatively quickly from the intestinal tract and will be used as a
metabolic fuel. An elevated RQ is characteristic of this oxidation
state. The fat, with its longer residence time in the intestinal tract and slower rate of use as fuel, will result in a lower RQ when it
serves as the metabolic fuel. Indeed, in the Sprague-Dawley rats, this
is what we observed. These rats, when fed the stock diet or the low-fat
diet, had larger excursions in RQ between the light and dark periods,
yet differences between light and dark periods of feeding were smaller
when the Sprague-Dawley rats were offered the high-fat diet. This diet
effect was also observed in the BHE/Cdb rats, but the peaks and nadirs
in the RQ were far closer in this strain than in the Sprague-Dawley
rats fed the high-fat diet. The circadian rhythms of feeding and RQ
were muted to a greater extent than in the Sprague-Dawley rats. When
the low-fat or stock diet was offered, the RQs were, in general, higher in the BHE/Cdb rats than in similarly fed Sprague-Dawley rats. As the
BHE/Cdb rats aged, they shifted their feeding and RQ patterns, whereas
the Sprague-Dawley rats did not.
The question that arises is why this should occur. The central
integrator of these rhythms clearly is of environmental and genetic
origin. In a recent, thought-provoking article, Sassone-Corsi (26) described self-sustaining clocks that master time by
gene regulation. In the present instance of rats having a normal or an
abnormal base sequence in their mitochondrial genome and provided diets
that differed in composition, we found an interactive effect of
genetics and nutrition on these internal clocks. In fact, we provide
evidence of these interactive effects that alter the shifts in
time-related biological functions, and we suspect that these shifts are
related to life span as well as disease development. Our previous
studies of longevity of BHE/Cdb rats showed that when they were fed
high-fat diets, life span was decreased and the time frame for
degenerative change in the pancreatic islets and the kidneys was
compressed. The shifts in feeding pattern and corresponding shifts in
intermediary metabolism as described here might thus have relevance to
life span and the time course of degenerative disease development.
It is known that rats of the BHE/Cdb strain have a mutated
mitochondrial genome and a tendency to develop age-related glucose intolerance (4, 6, 7,
21-24). We have also shown that the composition of
the diet influences the age at which this intolerance occurs
(6, 7). The results of the present study
suggest that shifts in the circadian rhythms of feeding occur as the
animal attempts to regulate its metabolism so as to forestall abnormal glucose homeostasis. These rats have a twofold increase in de novo
fatty acid synthesis when fed a low-fat or stock diet compared with
rats of other strains. They also have an increase in lipolytic rate
(10), which suggests that fatty acids are choice metabolic fuels. The high rate of fatty acid synthesis could artificially elevate
the RQ. However, the high-fat diet should suppress de novo fatty acid
synthesis, and the RQ should fall as a result (Figs. 5C and
6C). Although elevated fatty acid synthesis can explain in
part the RQ, one should also realize that glucose carbon recycling also
occurs to a greater extent in the BHE/Cdb rat than in the normal rat.
Increased gluconeogenesis and increased glycogen turnover as well as
glucose oxidation could influence the RQ pattern. Glucose turnover is
likewise influenced by diet composition. Altogether then, these
observations suggest that the genomic mutation has subtle effects on
metabolic flux that, in turn, influence the feeding pattern and the RQ.
Indeed, it is conceivable that the BHE/Cdb rats adapt to their mutation
(5), such that these aberrant metabolic patterns suppress
the normal day-night feeding and respiratory patterns. The age- and
diet-related increases in serum triglycerides and glycerol that
characterize this rat strain indicate a greater dependence on fatty
acid recycling. This too would influence the circadian rhythms of
feeding and respiration. As the BHE/Cdb rats fed the high-fat diet
began to lose control of glucose homeostasis and rely more on fatty
acids as metabolic fuel, they shifted their feeding pattern, and this
resulted in a shift in their RQ rhythm. These rats were responding to
some internal cue that abolished the day-night circadian rhythm in
feeding that is usually observed in rodents. We suspect that this cue
might originate with the mitochondrial defect that reduces ATP
synthesis efficiency (8). That a reduction in ATP
synthesis efficiency could occur can be deduced from the RQs and from
the heat production that rises as the animal ages. An increase in heat
production due to some sort of mitochondrial slippage would be
expected, and indeed we observed this to occur.
Perspectives
How relevant are these observations to the human? Recently,
several reports appeared in the literature documenting mutations in the
mitochondrial genome that associate with non-insulin-dependent diabetes
mellitus (1, 2, 21). Many years
ago, Jarrett and others (11, 14,
15, 27) reported that the normal diurnal rhythm in glucose tolerance was lost as humans progress toward non-insulin-dependent diabetes mellitus. These changes in rhythm were
associated with losses in the rhythms of blood glucose, insulin sensitivity, growth hormone, and fatty acids, suggesting that prediabetic humans, like the BHE/Cdb rats, adjust their metabolic patterns in an effort to retain some control of glucose homeostasis. The humans studied by Jarrett and colleagues were not genetically screened, so we do not know whether the rat-human comparison is valid.
However, given our present knowledge of the incidence of mitochondrial
DNA defects and diabetes, perhaps the comparison has some merit.
Further studies of prediabetic humans with mitochondrial defects should
be conducted to determine whether such shifts do occur and are relevant
to our understanding of how the body accommodates its aberrant
mitochondrial metabolism when such metabolism is abnormal.
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ACKNOWLEDGEMENTS |
This work was supported by the Georgia Agricultural Experiment
Station and The University of Georgia Diabetes Research Fund.
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FOOTNOTES |
Present address of C. E. Mathews: The Jackson Laboratory, Bar
Harbor, ME 04609-1500.
Address for reprint requests and other correspondence: C. D. Berdanier, Dept. of Foods and Nutrition, University of
Georgia, Athens, GA 30602-3622 (E-mail:
cberdani{at}hestia.fcs.uga.edu).
1
F1 crosses of these strains were also
studied in experiments 1-3 (21). Their
feeding behavior and RQ patterns were identical to those of their
mothers. That is, progeny of BHE/Cdb female and Sprague-Dawley male
rats were identical to BHE/Cdb full breds, and progeny of
Sprague-Dawley female with BHE/Cdb male rats were identical to the SD
full breds.
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 2 April 1999; accepted in final form 4 February 2000.
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