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3-adrenoreceptor
blockade attenuate acute exercise-induced reductions in leptin
mRNA?
1 Exercise and Nutrition Program and 2 Neurosciences Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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We investigated the effect of a single bout of
exercise on leptin mRNA levels in rat white adipose
tissue. Male Sprague-Dawley rats were randomly assigned to
an exercise or control group. Acute exercise was performed on a rodent
treadmill and was carried out to exhaustion, lasting an average of 85.5 ± 1.5 min. At the end of exercise, soleus muscle and liver glycogen
were reduced by 88% (P < 0.001).
Acutely exercised animals had lower (P < 0.05) leptin mRNA levels in retroperitoneal but not epididymal fat, and this was independent of fat pad weight. To test the hypothesis that
3-adrenergic-receptor
stimulation was involved in the downregulation of leptin mRNA in
retroperitoneal fat, a second experiment was performed in which rats
were randomized into one of four groups: control, control + 3-antagonist, exercise, and
exercise + 3-antagonist. A
highly selective 3-antagonist
(SR-59230A) or vehicle was given by gavage 30 min before exercise or
control experiment. Exercise consisted of 55 min of treadmill running,
sufficient to reduce liver and muscle glycogen by 70 and 80%,
respectively (both P < 0.0001). Again, acute exercise reduced leptin mRNA in retroperitoneal fat (exercise vs. control; P < 0.05), but 3-antagonism blocked this effect (exercise + 3-antagonist vs. control + 3-antagonist; P = 0.42). Unexpectedly, exercise
increased serum leptin. This would be consistent with the idea that
there are releasable, preformed pools of leptin within adipocytes. We
conclude that 3-receptor stimulation is a mechanism by which acute exercise downregulates retroperitoneal adipose tissue leptin mRNA in vivo.
adipose tissue; insulin; sympathetic nervous system; energy expenditure; ob gene
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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LEPTIN IS A PROTEIN HORMONE product of the mouse ob gene, and it is thought to regulate body energy balance through control of appetite, functioning as a satiety factor (2, 26, 36). In normal mice, rats, and humans, serum leptin levels are positively related to body fat, and diet-induced weight (fat) loss is accompanied by significant reductions in expression and circulating levels of leptin (4, 5, 7, 15). Our laboratory has shown that 7 wk of exercise training, in the form of voluntary wheel running, decreased body fat in male Osborne-Mendel and S5B/Pl rats (35). The exercise groups of both strains also had reduced levels of leptin mRNA in white adipose tissue, as well as lower circulating levels of leptin (35). However, it was not possible to ascertain whether the reduction in leptin was due to the reduced body fat or was a direct result of exercise. Zheng et al. (38) have compared the effect of chronic vs. a single bout of exercise (which does not alter body fat mass) on leptin expression. Their findings suggest that reduction in leptin mRNA was a direct result of acute exercise.
3-Adrenergic-receptor
stimulation regulates leptin expression in white adipose tissue (3, 10,
23). For example, norepinephrine acts on
3-adrenergic receptors and
inhibits leptin expression through a cAMP-dependent pathway (10). The
sympathetic nervous system is stimulated during exercise, resulting in
an increase in circulating catecholamines (16). We hypothesized that
catecholamines released during exercise act on
3-adrenergic receptors in
adipose tissue, and this results in downregulation of leptin mRNA.
The purpose of this investigation was twofold: first, to verify that
acute exercise reduces adipose tissue leptin mRNA and, second, to
address the extent to which
3-adrenergic-receptor stimulation is involved in this response. To test the hypothesis that
exercise activation of
3-adrenergic receptors in white
adipose tissue is responsible for the downregulation of leptin mRNA in rats, we administered SR-59230A, a
3-selective adrenergic-receptor blocking agent, before exercise (9, 22).
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Study Conditions
Animals. Male Sprague-Dawley rats were used in this study. The rats were purchased from Harlan Sprague-Dawley. They were 2 mo old and weighed ~250 g on arrival at the Pennington Biomedical Research Center vivarium, which is an animal care facility accredited by the American Association for Accreditation of Laboratory Animal Care. All rats were housed individually in Plexiglas cages (with bedding) in a temperature-controlled room (21-23°C). Rodent laboratory chow (5001 pellets, PMI Feeds, St. Louis, MO) was put on a wire rack placed over the top of the cage, and the rats were allowed to eat ad libitum throughout the experiment. A water bottle was attached to each cage, and it was changed daily. The animal room was on a 12:12-h light-dark cycle with lights on at 7 AM. All animal procedures were approved by the Animal Welfare Committee of the Pennington Biomedical Research Center.
Chemicals.
A 0.5% carboxymethylcellulose (C 5678, Sigma Chemical) solution was
used as a vehicle to administer the
3-antagonist and was also used
as a placebo. The selective
3-antagonist, SR-59230A, was
supplied by Dr. L. Manara (Research Centre Sanofi Midy, Milan, Italy).
SR-59230A is a 3-(2-ethylphenoxy)
1-[(1S)-1,2,3,4-tetrahydronaphth-1- yl-amino]-(2S)-2-propanol
oxalate, and it belongs to the aryloxypropanolaminotetralin class of
-adrenoreceptor-blocking agents. It is a highly selective 3-antagonist that, at 20 mg/kg,
has been shown to inhibit the thermogenic response of rat brown adipose
tissue to selective 3-agonists
(22). Furthermore, in rat white adipose tissue, SR-59230A has been
shown to antagonize
3-receptor-agonist-induced lipolysis (9).
Exercise familiarization. All animals were accustomed to exercise before experimentation by running on a rodent treadmill (Columbus Instruments, Columbus, OH) for 10 min per exposure, at 22 m/min and a 5% incline. Duration and frequency were kept to a minimum to ensure that training adaptations did not occur.
Experiment 1
The purpose of this experiment was to test the hypothesis that acute exercise, which does not alter fat pad weight, results in reduced leptin mRNA levels in white adipose tissue. Seventeen animals were randomly assigned to either an exercise (n = 9) or control (n = 8) group. Rats in the exercise group were run until exhaustion while the treadmill incline was fixed at 5%. For the first 5 min, animals ran at 15 m/min, followed by 10 min at 18 m/min, 15 min at 20 m/min, and then +2 m/min until 28 m/min. Treadmill belt speed was maintained at 28 m/min until exhaustion, which was defined as the point at which rats refused to run despite continual prodding. Only two rats were run at a time, and the exercise bouts were started 4 h after removal of food. Control rats were placed in a different Plexiglas cage (no bedding, without food and water) in the same room with the running rats. Rats were killed by decapitation immediately after the run, as were an equal number of control animals. Blood was collected for serum analyses. A part of the liver, soleus muscle, and retroperitoneal and epididymal fat pads was dissected, weighed, frozen in liquid nitrogen, and stored at
80°C until
later analyses.
Experiment 2
The purpose of this experiment was to test the hypothesis that administration of a3-adrenergic-receptor
antagonist would block the reduction in white adipose tissue leptin
mRNA that occurs during acute exercise. After exercise familiarization,
animals were randomly assigned to one of the following four groups:
control + vehicle (n = 8), exercise + vehicle (n = 8), control + SR-59230A (20 mg/kg body wt; n = 6), or exercise + SR-59230A (20 mg/kg body wt; n = 6).
Rats in the exercise groups were run on a motor-driven treadmill for 55 min in the following manner: 5 min at 22 m/min, 40 min at 27 m/min, 5 min at 22 m/min, and 5 min at 27 m/min. Only three rats were run at a
time, and the exercise bouts were started 4 h after the removal of food
and ~30 min after tube-fed vehicle or SR-59230A (20 mg/kg). Control
rats were also tube fed vehicle or SR-59230A and were killed by
decapitation ~1.5 h later. Thus all rats, exercise and control, were
killed 1.5 h after tube feeding. At death, blood was collected for
serum analyses. A part of the liver, soleus muscle, and retroperitoneal
and epididymal fat pads was dissected, weighed, frozen in liquid
nitrogen, and stored at 80°C until later analyses. The
carcasses were cleaned and stored at 20°C until body
composition analyses were performed.
Analytic Procedures
Serum analyses. Blood was collected for the following analyses: serum glucose, insulin, corticosterone, free fatty acids (FFA), and leptin. Glucose was analyzed by an enzymatic method (procedure no. 16-UV, Sigma Diagnostics), serum leptin and insulin concentrations were determined by RIA by using rat-specific antibodies (Linco Research, St. Charles, MO), corticosterone was also determined by RIA (ICN Biomedicals, Irvine, CA), and FFA (experiment 2 only) were determined with an enzymatic colormetric method (Wako Diagnostics, Richmond, VA).
Muscle and liver glycogen. Soleus muscle and liver samples were homogenized in weak acid (0.03 N HCl), and glycogen was measured fluorometrically essentially as described by Passonneau and co-workers (20, 25), with correction for free glucose.
Leptin mRNA determination. Total RNA was extracted from epididymal and retroperitoneal adipose tissue by using TriZol reagent (GIBCO-BRL, Gaithersburg, MD). RNA yield was determined spectrophotometrically, and integrity was determined by agarose gel electrophoresis. Rodent leptin mRNA was detected by Northern blot analysis by using a 320-bp cDNA probe derived by PCR from rat retroperitoneal adipose tissue, as previously described (13). The relative level of leptin mRNA was standardized against 28S rRNA and is expressed in arbitrary units.
Carcass body composition (experiment 2 only). Carcass composition was determined as previously described by Harris and Martin (11, 12). Briefly, autoclaved cold carcasses were homogenized with an equal weight of distilled water, and separate analyses were performed to measure carcass water, ash, and fat. Triplicate aliquots of the homogenates were dried at 80°C to constant weight for determination of carcass water. The same dried samples were held at 500°C overnight for determination of carcass ash. Three 10-ml aliquots of the homogenates were extracted with chloroform-methanol for measurement of carcass fat content.
Statistical Analysis
Data are presented as means ± SE, and statistical significance was set at P < 0.05. For experiment 1, Student's unpaired t-tests were used to detect differences between acutely exercised and control animals for all dependent variables measured. Data from experiment 2 were analyzed by using two-way analysis of variance with group (control and exercise) and treatment (placebo and3-antagonist) as factors.
Pairwise comparison of least squares means from the adopted model
allowed us to test components of the overall interaction that were of
greatest interest (i.e., control vs. exercise, and control + 3-antagonist vs. exercise + 3-antagonist). Data were analyzed by using SAS for Windows (version 6.12, SAS, Cary, NC).
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Experiment 1
The average run time to exhaustion was 85.5 ± 1.5 min, and acutely exercised animals had low soleus muscle and liver glycogen levels (Table 1).
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Compared with control animals, leptin mRNA levels in retroperitoneal
fat were significantly lower (Fig. 1;
P < 0.05) in the exercise
group. On the other hand, leptin mRNA in epididymal fat was similar
between exercise and control groups. For control animals, leptin mRNA
was higher in retroperitoneal than in epididymal fat (Fig. 1;
P < 0.01).
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Retroperitoneal and epididymal fat pad weights for the exercise and control groups were comparable. For retroperitoneal fat, the exercise group fat pad weight averaged 1.24 ± 0.08 g, whereas that for the control group averaged 1.41 ± 0.08 g. For epididymal fat, the exercise group fat pad weight averaged 2.88 ± 0.14 g, whereas that for control averaged 3.19 ± 0.13 g. Total body weight, measured before treadmill running, was also similar in the exercise and control groups, averaging 384 ± 6 and 381 ± 5 g, respectively.
Serum glucose and insulin were lower
(P < 0.01) in the acutely exercised
animals. Serum corticosterone was significantly elevated (P < 0.05) in the exercise group.
Serum leptin levels tended to be higher in the exercise group, but this
was not statistically significant (Table
2).
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Experiment 2
At the end of the 55-min treadmill protocol, all exercised animals exhibited low soleus muscle and liver glycogen levels (Table 1).Again, exercised animals had lower levels of leptin mRNA in
retroperitoneal fat (Fig.
2A,
exercise main effect, P < 0.05). Pairwise comparison of least squares means revealed that leptin mRNA
levels for the exercise group were lower than for control (P < 0.05), but that leptin mRNA
levels for control + 3-antagonist and exercise + 3-antagonist were not
statistically different (P = 0.42). In
epididymal fat, there were no significant differences in leptin mRNA
levels between exercise and control groups (Fig. 2B); however, animals receiving
SR-59230A exhibited higher leptin mRNA (treatment main effect,
P < 0.05).
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Acute exercise was not associated with an increase in serum FFA, but
FFA levels were higher in animals receiving SR-59230A (treatment main
effect, P < 0.05). Serum leptin
levels were higher, and insulin levels were lower, in the exercise
groups (exercise and exercise + 3-antagonist; exercise main
effect for both, P < 0.05). Pairwise
comparison of least squares means for insulin indicated that exercise + 3-antagonist animals had lower
levels than control + 3-antagonist animals
(P < 0.01), but insulin levels for
control and exercise alone were not statistically different (P = 0.27). Serum glucose was the same
across groups, whereas corticosterone levels were elevated in the
exercise groups (exercise main effect,
P < 0.001). Serum values for FFA,
leptin, insulin, glucose, and corticosterone can be found in Table
3.
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Data for body composition are listed in Table
4. There were no differences in percent
body fat, water, and ash among the four groups of animals. Similarly,
retroperitoneal and epididymal fat pad weights were the same across the
control, exercise, control + 3-antagonist, and exercise + 3-antagonist groups.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Our laboratory has previously shown that voluntary
wheel running in rats decreases both adipose tissue mRNA and
circulating levels of leptin (35). The decrease in leptin was related
to reductions in fat mass and cell size associated with exercise training. This observation was in agreement with the findings of
Friedman et al. (8), who showed that 8-12 wk of treadmill exercise
training reduced fat mass and leptin mRNA in lean and obese
SHHF/Mcc-facp rats. What was
unclear from these studies was whether exercise, independent of changes
in fat mass and cell size, could reduce white adipose tissue leptin
mRNA. Catecholamines, -agonists, and agents that increase cellular
levels of cAMP all acutely reduce leptin mRNA (32, 34). Because
exercise significantly increases the activity of the sympathoadrenal
system, we hypothesized that acute exercise would result in reduced
white adipose tissue leptin mRNA immediately postexercise. Findings
from experiment 1 demonstrate that a
single bout of treadmill exercise in male Sprague-Dawley rats is
sufficient to reduce leptin mRNA in retroperitoneal but not epididymal
fat. Reduced leptin mRNA in retroperitoneal fat after acute exercise
was independent of a decline in fat mass.
Noradrenaline given to mice by subcutaneous injection reduces leptin
expression in white adipose tissue by >50% (34), whereas specific
3-adrenergic agonists also
suppress leptin mRNA levels (3, 19). During exercise, catecholamine
activation of adrenoreceptors on adipose tissue leads to lipid
mobilization. Activation of lipolysis in this manner could initiate a
signaling cascade that suppresses leptin mRNA. The purpose of the
second experiment was to test the hypothesis that
3-adrenergic-receptor
stimulation during acute exercise is responsible for the downregulation
of leptin mRNA. First, we confirmed our initial observation that acute
exercise reduces leptin mRNA in retroperitoneal, but not epididymal,
white adipose tissue. However, leptin mRNA levels in retroperitoneal fat after administration of the
3-antagonist were similar in exercised and control animals, suggesting that
3-receptor activation is
involved in the downregulation of leptin mRNA. A complete block of the
exercise effect was not observed, as leptin mRNA levels for exercise + 3-antagonist were not
statistically different from those of exercise alone
(P = 0.20). Reduction in leptin mRNA during acute exercise likely involves a combination of mechanisms. Previous studies have shown that insulin levels are related to leptin
expression (24, 31, 37) and that rats subjected to streptozotocin-induced diabetes experience a complete suppression of
leptin mRNA (21). Exercise and
3-blocked animals tended to
have the lowest insulin level, and this likely explains the partial
reduction in leptin mRNA, even under conditions of
3-receptor antagonism.
We have shown that activation of
3-receptors during exercise is
involved in the downregulation of leptin mRNA. Accordingly, blood flow,
which is important for catecholamine (-receptor agonist) delivery,
may mediate this response. It has been shown that, at rest, rat
retroperitoneal fat receives twice the blood flow as epididymal fat
(6). If this regional difference in blood flow were to be maintained
during exercise, greater potential for catecholamine delivery to
retroperitoneal fat would exist. This could explain why leptin mRNA was
reduced in retroperitoneal, but not epididymal, fat after acute
exercise. To our knowledge, no study has directly compared metabolic
and lipolytic capabilities of rat retroperitoneal and epididymal fat,
but regional differences in -adrenoreceptor type, density, and
function (1) and hormone-sensitive lipase mass and function (18, 33)
could exist. Thus blood flow and metabolic potential, as well as direct
sympathetic activation of fat pads, may predict how leptin mRNA levels
are influenced by acute and/or chronic exercise.
Reduction in white adipose tissue leptin mRNA after acute exercise was also found in a study by Zheng et al. (38). They reported a 30% reduction in epididymal and periuterine fat after 60-120 min of treadmill running in male and female rats, respectively. Under our exercise conditions, we found leptin mRNA to be reduced in retroperitoneal but not epididymal fat. Zheng et al. did not report on leptin mRNA in retroperitoneal fat, and 6 of their 10 acutely exercised animals were female, each running at 30 m/min up an 8% grade for a total of 120 min. Thus gender and the ability to perform long-duration high-intensity exercise may be factors that contribute to the leptin mRNA response during acute exercise.
In humans, acute exercise appears to have no effect on serum leptin
levels (14, 27) or adipose tissue production of leptin (28). In
experiment 2, we found that acute
exercise, independent of
3-receptor antagonism, was
associated with high serum leptin. Kirchgessner et al. (17) recently
reported that tumor necrosis factor (TNF)-
-treated mice exhibited
high, whereas TNF--deficient mice had low, serum leptin levels.
Furthermore, they reported that TNF- treatment of 3T3-L1 adipocytes
results in rapid accumulation of leptin in cell culture media. Their
work suggests the existence of regulatable, preformed pools of leptin
within adipocytes and that TNF- can stimulate leptin release. Our
data are consistent with the idea that, in rats, exercise also
stimulates leptin release from a storage site within adipocytes but
that this is dependent on the duration of exercise. When exercise time
was fixed at 55 min, serum leptin was increased. When rats exercised
for >80 min, no significant increase in serum leptin was observed,
suggesting that the stored pool of leptin had been depleted. Precise
identification of an exercise time course for serum leptin changes in
the rat is beyond the scope of the present study. Additional
experiments will be required to confirm that moderate-intensity
treadmill running for <1 h is sufficient to increase serum leptin
levels in rats. Interestingly, the increase in serum leptin corresponds to previous experiments that have found exercise to induce an anorectic
effect in rats (30); therefore, leptin may be acting as a satiety
factor immediately postexercise.
It is interesting that the
3-receptor antagonist increased
FFA and that there was a trend for the exercise + 3-antagonist animals to have
the highest levels. Blockade of the
3-receptor may have increased
the responsiveness of the 1-
and 2-receptors for
adrenoreceptor-mediated lipolysis, resulting in the higher FFA
levels. Normally, elevated FFA during exercise tends to spare muscle
glycogen use (29), but there was little evidence of this in exercise + 3-antagonist animals. Thus an
alternative explanation may be that SR-59230A blocks fatty acid uptake
or oxidation in vivo, thereby giving rise to higher serum FFA.
Unfortunately, the present experiments were not designed to fully
characterize 3-receptor-antagonism effects
on serum FFA turnover and/or oxidation.
In summary, we have shown that acute exercise in rats reduces leptin
mRNA in retroperitoneal but not epididymal fat. A partial block of the
reduction in leptin mRNA after acute exercise was accomplished through
the administration of a
3-receptor antagonist (SR-59230A). This provides direct in vivo evidence that the
3-receptor in adipose tissue is
involved in the regulation of leptin expression. Because
3-receptor antagonism did not
completely block exercise-induced downregulation of leptin mRNA, other
factors such as low serum insulin contribute to this response.
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ACKNOWLEDGEMENTS |
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This study was supported, in part, by Department of Defense contract no. DAAH04-93-G-0298.
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FOOTNOTES |
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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.
Address for reprint requests and other correspondence: J. J. Zachwieja, Pennington Biomedical Research Center, Louisiana State Univ., 6400 Perkins Road, Baton Rouge, LA 70808 (E-mail: zachwijj{at}mhs.pbrc.edu).
Received 8 February 1999; accepted in final form 19 July 1999.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Arner, P.,
L. Hellstrom,
H. Wahrenberg,
and
M. Bronnegard.
Beta-adrenoreceptor expression in human fat cells from different regions.
J. Clin. Invest.
86:
1595-1600,
1990.
2.
Campfield, A. L.,
F. J. Smith,
Y. Guisez,
R. Devos,
and
P. Burn.
Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central networks.
Science
269:
546-549,
1995
3.
Collins, S.,
and
R. S. Surwit.
Pharmacologic manipulation of ob expression in a dietary model of obesity.
J. Biol. Chem.
271:
9437-9440,
1996
4.
Considine, R. V.,
E. L. Considine,
C. J. Williams,
M. R. Nyce,
S. A. Magosin,
T. L. Bauer,
E. L. Rosato,
J. Colberg,
and
J. F. Caro.
Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity.
J. Clin. Invest.
95:
2986-2988,
1995.
5.
Considine, R. V.,
S. K. Madhur,
M. L. Heiman,
A. Kriauciunas,
T. W. Stephens,
M. R. Nyce,
J. P. Ohannesian,
C. C. Marco,
L. J. McKee,
T. L. Bauer,
and
J. F. Caro.
Serum immunoreative-leptin concentrations in normal-weight and obese humans.
N. Engl. J. Med.
334:
292-295,
1996
6.
Crandall, D. L.,
B. M. Goldstein,
F. Huggins,
and
P. Cervoni.
Adipocyte blood flow: influence of age, anatomic location, and dietary manipulation.
Am. J. Physiol.
247 (Regulatory Integrative Comp. Physiol. 16):
R46-R51,
1984.
7.
Frederich, R. C.,
A. Hamann,
S. Anderson,
B. Lollmann,
B. B. Lowell,
and
J. S. Flier.
Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action.
Nature Med.
1:
1311-1314,
1995[Medline].
8.
Friedman, J. E.,
C. M. Ferrara,
K. S. Aulak,
M. Hatzoglou,
S. A McCune,
S. Park,
and
W. M. Sherman.
Exercise training down-regulates ob gene expression in the genetically obese SHHF/Mcc-facp rat.
Horm. Metab. Res.
29:
214-219,
1997[Medline].
9.
Galitzky, J.,
D. Langin,
P. Verwaerde,
J.-L. Montastruc,
M. Lafontan,
and
M. Berlan.
Lipolytic effects of conventional exercise 3-adrenoceptor agonists and of CGP 12,177 in rat and human fat cells: preliminary pharmacological evidence for a putative 4-adrenoceptor.
Br. J. Pharmacol.
122:
1244-1250,
1997[Medline].
10.
Gettys, T. W.,
P. J. Harkness,
and
P. M. Watson.
The 3-adrenergic receptor inhibits insulin-stimulated leptin secretion from isolated rat adipocytes.
Endocrinology
137:
4054-4057,
1996[Abstract].
11.
Harris, R. B. S.
The impact of high- or low-fat cafeteria foods on nutrient intake and growth of rats consuming a diet containing 30% energy as fat.
Int. J. Obes.
17:
307-315,
1993.
12.
Harris, R. B. S.,
and
R. J. Martin.
Metabolic response to a specific lipid-depleting factor in parabiotic rats.
Am. J. Physiol.
250 (Regulatory Integrative Comp. Physiol. 19):
R276-R286,
1986
13.
Harris, R. B. S.,
T. G. Ramsay,
S. R. Smith,
and
R. C. Bruch.
Early and late stimulation of ob mRNA expression in meal-fed and overfed rats.
J. Clin. Invest.
97:
2020-2026,
1996[Medline].
14.
Hickey, M. S.,
J. A. Houmard,
R. V. Considine,
G. L. Tyndall,
J. B. Midgette,
K. E. Gavigan,
M. L. Weidner,
M. R. McCammon,
R. G. Israel,
and
J. F. Caro.
Gender-dependent effects of exercise training on serum leptin levels in humans.
Am. J. Physiol.
272 (Endocrinol. Metab. 35):
E562-E566,
1997
15.
Igel, M.,
H. Kainulainen,
A. Brauers,
W. Becker,
L. Herberg,
and
H. G. Joost.
Long-term and rapid regulation of ob mRNA levels in adipose tissue from normal (Sprague-Dawley rats) and obese (db/db mice, fa/fa rats) rodents.
Diabetologia
39:
758-765,
1996[Medline].
16.
Ji, L. L.,
D. L. F. Lennon,
R. G. Kochan,
F. J. Nagle,
and
H. A. Lardy.
Enzymatic adaptation to physical training under -blockade in the rat.
J. Clin. Invest.
78:
771-778,
1986.
17.
Kirchgessner, T. G.,
K. T. Uysal,
S. M. Wiesbrock,
M. W. Marin,
and
G. S. Hotamisligil.
Tumor necrosis factor- contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes.
J. Clin. Invest.
100:
2777-2782,
1997[Medline].
18.
Lafontan, M.,
M. Berlan,
J. Galitzky,
and
J. L. Montastruc.
Alpha-2 adrenoceptors in lipolysis: 2 antagonists and lipid-mobilizing strategies.
Am. J. Clin. Nutr.
55:
219S-227S,
1992
19.
Li, H.,
M. Matheny,
and
P. J. Scarpace.
3-Adrenergic-mediated suppression of leptin gene expression.
Am. J. Physiol.
272 (Endocrinol. Metab. 35):
E1031-E1036,
1997
20.
Lust, W. D.,
J. V. Passonneau,
and
S. K. Crites.
The measurement of glycogen in tissues by amylo--1,4--1,6-glucosidase after the destruction of preexisting glucose.
Anal. Biochem.
68:
328-331,
1975[Medline].
21.
MacDougald, O. A.,
C. S. Hwang,
H. Fan,
and
M. D. Lane.
Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes.
Proc. Natl. Acad. Sci. USA
92:
9034-9037,
1995
22.
Manara, L.,
D. Badone,
M. Barone,
G. Boccardi,
R. Cecche,
T. Croci,
A. Giudice,
U. Guzzi,
M. Landi,
and
G. Le Fur.
Functional identification of rat atypical -adrenoreceptors by the first 3-selective antogonists, aryloxypropanolaminotetralins.
Br. J. Pharmacol.
117:
435-442,
1996[Medline].
23.
Mantzoros, C. S.,
D. Qu,
R. C. Frederich,
V. S. Susulic,
B. B. Lowell,
E. Maratos-Flier,
and
J. S. Flier.
Activation of 3 adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice.
Diabetes
45:
909-914,
1996[Abstract].
24.
Mizuno, T. M.,
H. Bergen,
T. Funabashi,
S. P. Kleopoulos,
Y. G. Zhong,
W. A. Bauman,
and
C. V. Mobbs.
Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.
Proc. Natl. Acad. Sci. USA
93:
3434-3438,
1996
25.
Passonneau, J. V.,
P. D. Gatfield,
D. W. Schulz,
and
O. H. Lowry.
An enzymatic method for measurement of glycogen.
Anal. Biochem.
19:
315-326,
1967[Medline].
26.
Pelleymounter, M. A.,
M. J. Cullen,
M. B. Baker,
R. Hecht,
D. Winters,
T. Boodne,
and
F. Collins.
Effects of the obese gene product on body weight regulation in ob/ob mice.
Science
269:
540-543,
1995
27.
Perusse, L.,
G. Collier,
J. Gagnon,
A. S. Leon,
D. C. Rao,
J. S. Skinner,
J. H. Wilmore,
A. Nadeau,
P. Z. Zimmet,
and
C. Bouchard.
Acute and chronic effects of exercise on leptin levels in humans.
J. Appl. Physiol.
83:
5-10,
1997
28.
Racette, S. B.,
S. W. Coppack,
M. Landt,
and
S. Klein.
Leptin production during moderate-intensity aerobic exercise.
J. Clin. Endocrinol. Metab.
82:
2275-2277,
1997
29.
Rennie, M. J.,
W. M. Winder,
and
J. O. Holloszy.
A sparing effect of increased free fatty acids on muscle glycogen content in the exercising rat.
Biochem. J.
156:
647-655,
1976[Medline].
30.
Rivest, S.,
and
D. Richard.
Involvement of corticotropin-releasing factor in the anorexia induced by exercise.
Brain Res. Bull.
25:
169-172,
1990[Medline].
31.
Saladin, R.,
P. De Vos,
M. Guerre-Millo,
A. Leturque,
J. Girard,
B. Stails,
and
J. Auwerx.
Transient increase in obese gene expression after food intake or insulin administration.
Nature
377:
527-529,
1995[Medline].
32.
Slieker, L. F.,
K. W. Sloop,
P. L. Surface,
A. Kriauciunas,
F. LaQuier,
J. Manetta,
J. Bue-Valleshey,
and
T. W. Stephens.
Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP.
J. Biol. Chem.
271:
5301-5304,
1996
33.
Sztalryd, C.,
and
F. B. Kraemer.
Differences in hormone-sensitive lipase expression in white adipose tissue from various anatomic locations of the rat.
Metabolism
43:
241-247,
1994[Medline].
34.
Trayhurn, P.,
J. S. Duncan,
and
D. V. Rayner.
Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system.
Biochem. J.
311:
729-733,
1995.
35.
Zachwieja, J. J.,
S. L. Hendry,
S. R. Smith,
and
R. B. S. Harris.
Voluntary wheel running decreases adipose tissue mass and expression of leptin mRNA in Osborne-Mendel rats.
Diabetes
46:
1159-1166,
1997[Abstract].
36.
Zhang, Y.,
R. Proenca,
M. Maffer,
M. Barone,
L. Leopold,
and
J. M. Friedman.
Positional cloning of the mouse obese gene and its human homologue.
Nature
272:
425-432,
1994.
37.
Zheng, D.,
J. P. Jones,
S. J. Usala,
and
G. L. Dohm.
Differential expression of ob mRNA in rat adipose tissues in response to insulin.
Biochem. Biophys. Res. Commun.
218:
434-437,
1996[Medline].
38.
Zheng, D.,
M. H. Wooter,
Q. Zhou,
and
G. L. Dohm.
The effect of exercise on ob gene expression.
Biochem. Biophys. Res. Commun.
225:
747-750,
1996[Medline].
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