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Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901 and * Obesity Research Center, St. Lukes-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY 10025
3To whom correspondence should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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4–7 h after meals. Increasing evidence indicates that insulin, in
concert with permissive effects of cortisol, can increase serum leptin
over this time frame and likely contributes to meal-induced
increases in serum leptin. Further research is required to elucidate
the cellular and molecular mechanisms underlying short- and
long-term nutritional and hormonal regulation of leptin production
and secretion.
KEY WORDS: • leptin • adipose tissue • insulin • glucocorticoid
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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),
including the decrease in metabolic rate that allows survival for
longer periods, inhibition along the reproductive and thyroid axes
(Ahima et al. 1997
, Kim et al. 2000
) and,
at least in rodents, the activity of the sympathetic nervous system
(Satoh et al. 1999
). Leptin is also a critical signal
for the onset of puberty (Ahima et al. 1997
). To understand fully the influence of nutritional status on leptin physiology, it is necessary to understand mechanisms regulating leptin production in the fat cell. In this brief review, we will summarize knowledge of the nutritional and hormonal regulation of leptin. We will focus on available data in humans and the roles of insulin, glucocorticoids and catecholamines.
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Leptin and human obesity. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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) and leptin
receptor defects (Clement et al. 1998
) in humans are
very rare. On average, serum leptin is usually elevated in obesity and
is positively correlated with body mass index, percentage of body fat
and fat mass (Considine et al. 1996
, Maffei et al. 1995
). However, several laboratories have noted a rather
wide range of plasma leptin values at any given level of body fat
(Considine et al. 1996
, Maffei et al. 1995
). Some obese subjects exhibit notably lower or higher
leptin levels than predicted from their body fat, suggesting that
mechanisms other than absolute fat mass per se regulate serum leptin.
This points to the possibility that a differential regulation of leptin
secretion contributes to the drive to maintain a high body weight in
some obese subjects.
The positive correlation between total body fat mass and serum leptin
is probably explained primarily by the increased release of leptin from
large compared with small fat cells (Lonnqvist et al. 1997
). On average, leptin release per gram of adipose tissue is
two times greater in obese than in lean subjects. Because fat cell size
is usually enlarged 2–4 times in the obese, when expressed per fat
cell, leptin secretion is up to 7 times higher in obese than in lean
subjects. In addition, an increased number of fat cells, particularly
in extreme obesity, undoubtedly contribute to increases in serum
leptin. An important unanswered question is whether the increased
production of leptin in enlarged fat cells from obese subjects results
from the chronic hormonal (i.e., hyperinsulinemia and perhaps increased
cortisol turnover) and paracrine (increased cytokine production within
adipose tissue) milieu associated with the obese state (Fig. 1
). In addition, a signal arising from the physical
"stretching" of the adipocyte has been proposed (Hamilton et al. 1995
).
|
). The mechanism involved is unclear, but one report
indicates a direct effect of estrogen to increase leptin production
(Casabiell et al. 1998
). The sex difference is
detectable even in utero and is attributable to the fetus itself
(Jaquet et al. 1998
). |
Acute and chronic nutritional regulation of leptin. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
|---|
, Maffei et al. 1995
,
Rosenbaum et al. 1997
) and decrease with weight loss
(Maffei et al. 1995
), consistent with leptin’s role as
a signal of the size of adipose tissue stores. However, superimposed on
the regulation of leptin secretion by level of obesity, acute
nutritional and hormonal signals modulate the rate of leptin secretion
with a time course encompassing effects up to 7 h
(Kolaczynski et al. 1996a
, Schoeller et al. 1997
). Serum leptin displays a diurnal rhythm with the
highest levels between 1100 and 0100 h, after which plasma leptin
declines until early afternoon (Sinha et al. 1996
). The
diurnal rhythm is linked to meal timing because a 6-h delay in meals
produces a similar phase shift in the plasma leptin profile
(Schoeller et al. 1997
). Furthermore, frequent blood
sampling reveals that plasma leptin levels are pulsatile, with 30
pulses per 24 h period (Licinio et al. 1997
,
Sinha et al. 1996
).
Plasma leptin declines gradually during 24–36 h of fasting to 40–70%
of baseline in both lean and obese subjects despite little or no loss
of fat mass (Boden et al. 1996
, Grinspoon et al. 1997
, Kolaczynski et al. 1996b
). Acute
massive overfeeding (120 kcal/kg) increases plasma leptin by 40% after
5 h (Kolaczynski et al. 1996a
). Compared
with a high fat diet (60% of calories), a low fat (20%), high
carbohydrate diet produces higher peaks of leptin during the night,
without affecting morning leptin levels (Havel et al. 1999
). Thus, it is important to consider the excursions in
plasma leptin that result from alterations in macronutrient composition
or meal-timing, in addition to effects on baseline (morning leptin
after an 18-h fast).
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Depot differences. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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, Van Harmelen et al. 1998
). These findings, coupled with the fact that visceral
adipose tissue usually accounts for only 5–10% of total body fat,
appear to explain why subcutaneous adipose tissue is the major
determinant of plasma leptin in multiple regression analyses
(Van Gaal et al. 1999
). |
Regulation of leptin production. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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Role of insulin. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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,
Pratley et al. 1996
) or that increases in plasma leptin
were evident only with prolonged hyperinsulinemia (several days)
(Boden et al. 1997
) or with supraphysiologic insulin
concentrations (Utriainen et al. 1996
). However, when
plasma leptin levels during physiologic insulin infusion are compared
with those of saline-infused controls at the same time of day, it
is clear that insulin either maintains or increases plasma leptin
levels, whereas levels in the control group decrease. Differences
between the groups were detectable within 1 h (Malmstrom et al. 1996
).
In vitro studies support a direct role for insulin in regulating leptin
production. We observed that 24 h of culture of subcutaneous human
adipose tissue fragments with 7 nmol/L insulin resulted in 50% higher
leptin release, compared with controls cultured without insulin,
without affecting leptin mRNA levels (Russell et al. 1998
). However, in cultures of newly differentiated human
adipocytes, insulin is critical for maintaining leptin mRNA levels and
leptin release over 24 h (Wabitsch et al. 1996
).
Results from studies of isolated human subcutaneous adipocytes show
much more delayed effects of insulin that are evident only after 72–96
h. Thus, different experimental systems appear to give discrepant
results on the role of insulin in regulating leptin. It is worth noting
that fragments of human fat secrete leptin at levels comparable to
those calculated from arteriovenous difference studies (Klein et al. 1996
), and that the direction, time course and mechanisms
of hormonal effects involved appear to model in vivo results well with
regard to insulin and other hormonal effects described below.
|
Role of glucose and glucosamine. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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). It is difficult to rule out this
factor from available data in human adipocytes, but it is notable that
the potentiation of insulin action on leptin by glucocorticoids
(described below) is not associated with increased glucose utilization
(Appel and Fried 1992
). It has also been suggested that
the flux of glucose through the glucosamine pathway serves as a
"nutrient sensing" system that upregulates leptin expression during
hyperinsulinemia, hypertriglyceridemia and in states of insulin
resistance (Wang et al. 1998
). The relative contribution
of substrate and hormonal effects in regulating leptin expression in
insulin-sensitive and insulin-resistant states will require
further investigation. |
Role of cortisol. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
|---|
). Furthermore, expression
of 11ß-hydroxysteroid dehydrogenase, the enzyme that interconverts
cortisone to cortisol, is higher in omental than subcutaneous fat,
suggesting that local concentrations of cortisol may vary among depots
(Ewart et al. 1999
). Available data indicate that
glucocorticoids potently stimulate leptin expression, but may also
induce central leptin resistance (Zakrzewska et al. 1997
). Thus, by affecting the balance between leptin
sensitivity and production, elevated glucocorticoids may favor fat
deposition and a higher set point for body fat. |
In vivo effects of glucocorticoid administration on leptin. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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) after as little as 9 h
(Miell et al. 1996
) and subcutaneous adipose tissue
leptin mRNA after 2 d (Kolaczynski et al. 1997
).
The increase in plasma leptin in response to glucocorticoid appears to
be greater in obese vs. lean humans (Dagogo-Jack et al. 1997
). Glucocorticoids induce insulin resistance and
hyperinsulinemia (Larsson and Ahren 1996
,
Papaspyrou-Rao et al. 1997
), thus raising the
possibility that the in vivo effects of glucocorticoid on leptin are
indirect. However, Larsson and Ahren (1996)
found that
the increases in plasma leptin with dexamethasone were not related to
changes in plasma insulin or insulin sensitivity. |
In vitro effects of glucocorticoids on leptin. |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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). After 24–48 h of
culture, dexamethasone increased leptin mRNA in both omental and
subcutaneous fat, but increased leptin release into the medium only in
omental fat. |
Interactions between insulin and glucocorticoid in leptin regulation |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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As in our results in cultured fragments of human fat, synergism between
insulin and cortisol in promoting leptin expression has been noted in
cultures of newly differentiated human fat cells (Wabitsch et al. 1996
). Contrasting these results, however, are reports that
dexamethasone actually decreases insulin-stimulated leptin release
into the medium from cultured isolated human adipocytes
(Considine et al. 1997
, Halleux et al. 1998
). The reason for this discrepancy is not known, but may
relate to the inclusion of serum in the culture medium.
Glucocorticoids, added with or without insulin, appear to increase
leptin by a transcriptional mechanism, as judged by inhibitor studies
(Bradley and Cheatham 1999
, Russell et al. 1998
). A glucocorticoid response element has been identified in
the promoter region of the human leptin gene, but there are no reports
on its functionality (Gong et al. 1996
).
Importance of cortisol in the regulation of leptin.
Given findings that cortisol potentiates insulin effects on leptin
expression, it may appear paradoxical that leptin and cortisol exhibit
reciprocal diurnal rhythms (Havel et al. 1999
,
Licinio et al. 1997
). This inconsistency may arise from
the failure to consider variability in serum insulin levels. According
to results from several in vitro models, glucocorticoids increase
leptin expression most strongly in the presence of insulin, with a time
delay of 3–7 h. Similarly, in vivo, in subjects who are fed (i.e.,
high insulin), administration of a bolus of dexamethasone induces
higher serum leptin levels compared with those administered saline
after 4–5 h, yet dexamethasone had no effect in subjects who had
fasted (Laferrère et al. 1998
). Our recently
reported preliminary data indicate that insulin also promotes a
dexamethasone-induced rise in serum leptin (Laferrère et al. 1999
), suggesting that the meal effect is due at least
in part to the rise in serum insulin. In addition, recent data from rat
studies indicate a potentially important role for gut peptides
(Attoub et al. 1999
).
The sympathetic nervous system and ß-adrenergic agonists.
There is ample evidence to suggest that short- or long-term
stimulation of adipose tissue ß-adrenergic receptors (ß-AR)
inhibits leptin in rodents and adipose cell lines (Li et al. 1997
, Trayhurn et al. 1995
). Increases in cyclic
AMP production may directly affect leptin mRNA transcription because a
cyclic AMP-responsive element has been identified in the promoter
region of the leptin gene (Gong et al. 1996
). In human
adipose tissue, we reported that isoproterenol has both short- and
long-term effects on leptin expression. Isoproterenol decreases
leptin release after 1.5–3 h of incubation of adipose tissue from
obese (Ricci and Fried 1999
) or lean subjects
(unpublished). Over the longer term, culture of human omental or
subcutaneous adipose tissue with isoproterenol for 24 h decreased
leptin accumulation in the medium in parallel with a decrease in its
mRNA level (Ricci and Fried 1999
). This occurs even when
insulin or insulin and/or dexamethasone are present in the incubation
medium (Halleux et al. 1998
, Ricci and Fried 1999
).
Consistent with the fairly rapid inhibitory effects of ß-AR
stimulation on leptin release, two studies have demonstrated that
infusion of isoproterenol or epinephrine (Carulli et al. 1999
) decreases plasma leptin by 19–27% over 120 min in lean
men and women (Donahoo et al. 1997
). A 3-h infusion of
epinephrine (at levels similar to that seen in strenuous exercise)
decreased plasma leptin by 22% and abdominal subcutaneous adipose
tissue leptin mRNA relative abundance by 47% in obese men and
women (Carulli et al. 1999
). We also found a
rapid decrease in serum leptin when sympathetic nervous system
activity was stimulated by placing women in a cold chamber at 4°C
(Ricci et al. 2000
). Using open-flow microperfusion
in subcutaneous human adipose tissue in vivo, Orban et al. (1999)
noted a transient decrease in interstitial fluid leptin
concentration within 90 min of addition of isoproterenol. It is
unlikely that fatty acids per se explain the decrease in leptin with
isoproterenol (Stumvoll et al. 2000
). Given the
relatively rapid effects of ß-adrenergic activation on leptin
release, we speculate that the pulsitility of leptin secretion in vivo
may be mediated in part by sympathetic innervation of adipose tissue.
There is precedent for this notion in the observation of Bergman that
fatty acid release from dog omental adipose tissue is pulsitile and
blocked by propanolol (Getty et al. 2000
)
Regulation of leptin secretion.
Virtually nothing is known about the cellular pathway(s) involved in
leptin secretion, i.e., whether leptin secretion per se is regulated
(increases/decreases in response to a secretagogue) or is merely
constitutively secreted at a rate proportional to its synthesis. The
fairly rapid effects of ß-adrenergic stimulation on leptin release
from adipose tissue in vivo and in vitro suggest the possibility that
leptin secretion per se is regulated by cAMP. A recent report suggests
that cholecystokinin may regulate leptin secretion directly
(Attoub et al. 1999
). Additionally, tumor necrosis
factor, potentially an important paracrine regulator of leptin,
transiently increases release of leptin from a preformed pool in 3T3-L1
adipocytes (Kirchgessner et al. 1997
).
A number of lines of evidence, derived mainly from studies of rodent
models, suggest that insulin directly influences leptin secretion.
Barr et al. (1997)
found that insulin stimulated leptin
release from rat adipocytes and that this efflux was associated with an
initial decrease in cellular leptin content. Using confocal microscopy,
Barr et al. (1997)
showed that in the absence of
insulin, intracellular leptin was localized to the endoplasmic
reticulum, whereas after insulin treatment, leptin was found at the
plasma membrane, consistent with the hypothesis that insulin directly
increased leptin secretion. Similarly, Bradley and Cheatham (1999)
found that incubation of rat adipocytes with insulin
increases leptin release during a 2-h incubation without affecting
leptin mRNA. Insulin increases the relative rate of release of a number
of adipocyte secretory proteins, independently of alterations in
protein synthesis (Scherer et al. 1995
). In the future,
it will be important to determine whether insulin also directly
influences the intracellular trafficking of leptin and the importance
of such mechanisms to short-term changes (minutes to hours) in
serum leptin in response to physiologic and nutritional signals.
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Summary and conclusions |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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FOOTNOTES |
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2 Supported by National Institutes of Health
grants RO1DK52398 (S.K.F.) and KO8 02572 (B.L.) and a grant from the
American Diabetes Association (B.L.).
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REFERENCES |
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TOPABSTRACTINTRODUCTIONLeptin and human obesity.Acute and chronic nutritional...Depot differences.Regulation of leptin production.Role of insulin.Role of glucose and...Role of cortisol.In vivo effects of...In vitro effects of...Interactions between insulin and...Summary and conclusionsREFERENCES |
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1. Ahima R. S., Dushay J., Flier S. N., Prabakaran D., Flier J. S. Leptin accelerates the onset of puberty in normal female mice. J. Clin. Investig. 1997;99:391-395[Medline]
2.
Appel B., Fried S. K. Effects of insulin and dexamethasone on lipoprotein lipase in human adipose tissue. Am. J. Physiol. 1992;262:E695-E699
3.
Attoub S., Levasseur S., Buyse M., Goiot H., Laigneau J. P., Moizo L., Hervatin F., Le Marchand-Brustel Y., Lewin J. M., Bado A. Physiological role of cholecystokinin B/gastrin receptor in leptin secretion. Endocrinology 1999;140:4406-4410
4.
Barr V. A., Malide D., Zarnowski M. J., Taylor S. I., Cushman S. W. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology 1997;138:4463-4472
5. Boden G., Chen X., Kolaczynski J. W., Polansky M. Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects. J. Clin. Investig. 1997;100:1107-1113[Medline]
6. Boden G., Chen X., Mozzoli M., Ryan I. Effect of fasting on serum leptin in normal human subjects. J. Clin. Endocrinol. Metab. 1996;81:3419-3423[Abstract]
7. Bradley R. L., Cheatham B. Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes. Diabetes 1999;48:272-278[Abstract]
8.
Carulli L., Ferrari S., Bertolini M., Tagliafico E., Del Rio G. Regulation of ob gene expression: evidence for epinephrine-induced suppression in human obesity. J. Clin. Endocrinol. Metab. 1999;84:3309-3312
9.
Casabiell X., Pineiro V., Peino R., Lage M., Camina J., Gallego R., Vallejo L. G., Dieguez C., Casanueva F. F. Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men. J. Clin. Endocrinol. Metab. 1998;83:2149-2155
10. Clement K., Vaisse C., Lahlou N., Cabrol S., Pelloux V., Cassuto D., Gourmelen M., Dina C., Chambaz J., Lacorte J. M., Basdevant A., Bougneres P., Lebouc Y., Froguel P., Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature (Lond.) 1998;392:398-401[Medline]
11. Considine R. V., Nyce M. R., Kolaczynski J. W., Zhang P. L., Ohannesian J. P., Moore J.H.J., Fox J. W., Caro J. F. Dexamethasone stimulates leptin release from human adipocytes: unexpected inhibition by insulin. J. Cell Biochem. 1997;65:254-258[Medline]
12.
Considine R. V., Sinha M. K., Heiman M. L., Kriauciunas A., Stephens T. W., Nyce M. R., Ohannesian J. P., Marco C. C., McKee L. J., Bauer T. L. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 1996;334:292-295
13. Dagogo-Jack S., Fanelli C., Paramore D., Brothers J., Landt M. Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes 1996;45:695-698[Abstract]
14.
Dagogo-Jack S., Selke G., Melson A. K., Newcomer J. W. Robust leptin secretory responses to dexamethasone in obese subjects. J. Clin. Endocrinol. Metab. 1997;82:3230-3233
15.
Donahoo W. T., Jensen D. R., Yost T. J., Eckel R. H. Isoproterenol and somatostatin decrease plasma leptin in humans: a novel mechanism regulating leptin secretion. J. Clin. Endocrinol. Metab. 1997;82:4139-4143
16. Ewart H. S., Carroll R., Severson D. L. Lipoprotein lipase activity is stimulated by insulin and dexamethasone in cardiomyocytes from diabetic rats. Can. J. Physiol. Pharmacol. 1999;77:571-578[Medline]
17.
Flier J. S. Clinical review 94: what’s in a name? In search of leptin’s physiologic role. J. Clin. Endocrinol. Metab. 1998;83:1407-1413
18. Getty L., Panteleon A. E., Mittelman S. D., Dea M. K., Bergman R. N. Rapid ascillations of free fatty acids in normal and fat-fed dogs are driven by the central nervous system, not by insulin. Obes. Res. 2000;7:33s(abs.)
19.
Gong D. W., Bi S., Pratley R. E., Weintraub B. D. Genomic structure and promoter analysis of the human obese gene. J. Biol. Chem. 1996;271:3971-3974
20.
Grinspoon S. K., Askari H., Landt M. L., Nathan D. M., Schoenfeld D. A., Hayden D. L., Laposata M., Hubbard J., Klibanski A. Effects of fasting and glucose infusion on basal and overnight leptin concentrations in normal-weight women. Am. J. Clin. Nutr. 1997;66:1352-1356
21.
Halleux C. M., Servais I., Reul B. A., Detry R., Brichard S. M. Multihormonal control of ob gene expression and leptin secretion from cultured human visceral adipose tissue: increased responsiveness to glucocorticoids in obesity. J. Clin. Endocrinol. Metab. 1998;83:902-910
22. Hamilton B. S., Paglia D., Kwan A. Y., Deitel M. Increased obese mRNA expression in omental fat cells from massively obese humans. Nat. Med. 1995;1:953-956[Medline]
23. Havel P. J., Townsend R., Chaump L., Teff K. High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes 1999;48:334-341[Abstract]
24.
Jaquet D., Leger J., Levy-Marchal C., Oury J. F., Czernichow P. Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation on serum leptin concentrations. J. Clin. Endocrinol. Metab. 1998;83:1243-1246
25. Kim M. S., Small C. J., Stanley S. A., Morgan D. G., Seal L. J., Kong W. M., Edwards C. M., Abusnana S., Sunter D., Ghatei M. A., Bloom S. R. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. J. Clin. Investig. 2000;105:1005-1011[Medline]
26. Kirchgessner T. G., Uysal K. T., Wiesbrock S. M., Marino M. W., Hotamisligil G. S. Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J. Clin. Investig. 1997;100:2777-2782[Medline]
27. Klein S., Coppack S. W., Mohamed-Ali V., Landt M. Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes 1996;45:984-987[Abstract]
28. Kolaczynski J. W., Considine R. V., Ohannesian J., Marco C., Opentanova I., Nyce M. R., Myint M., Caro J. F. Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves. Diabetes 1996b;45:1511-1515[Abstract]
29.
Kolaczynski J. W., Goldstein B. J., Considine R. V. Dexamethasone, OB gene, and leptin in humans; effect of exogenous hyperinsulinemia. J. Clin. Endocrinol. Metab. 1997;82:3895-3897
30.
Kolaczynski J. W., Ohannesian J. P., Considine R. V., Marco C. C., Caro J. F. Response of leptin to short-term and prolonged overfeeding in humans. J. Clin. Endocrinol. Metab. 1996a;81:4162-4165
31. Laferrère B., Fried S. K., Osborne T., Uy N., Kovera A., Albu J., Pi-Sunyer F. X. Synergistic effects in in vivo insulin and dexamethasone on serum leptin in humans. Obes. Res. 1999;7:65s (Abst.)
32.
Laferrère B., Fried S. K., Hough K., Campbell S. A., Thornton J., Pi-Sunyer F. X. Synergistic effects of feeding and dexamethasone on serum leptin levels. J. Clin. Endocrinol. Metab. 1998;83:3742-3745
33. Larsson H., Ahren B. Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. J. Clin. Endocrinol. Metab. 1996;81:4428-4432[Abstract]
34.
Li H., Matheny M., Scarpace P. J. ß3-Adrenergic-mediated suppression of leptin gene expression in rats. Am. J. Physiol. 1997;272:E1031-E1036
35. Licinio J., Mantzoros C., Negrao A. B., Cizza G., Wong M. L., Bongiorno P. B., Chrousos G. P., Karp B., Allen C., Flier J. S., Gold P. W. Human leptin levels are pulsatile and inversely related to pituitary-adrenal. Nat. Med. 1997;3:575-579[Medline]
36.
Licinio J., Negrao A. B., Mantzoros C., Kaklamani V., Wong M. L., Bongiorno P. B., Negro P. P., Mulla A., Veldhuis J. D., Cearnal L., Flier J. S., Gold P. W. Sex differences in circulating human leptin pulse amplitude: clinical implications. J. Clin. Endocrinol. Metab. 1998;83:4140-4147
37. Lonnqvist F., Nordfors L., Jansson M., Thorne A., Schalling M., Arner P. Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression. J. Clin. Investig. 1997;99:2398-2404
38. Maffei M., Halaas J., Ravussin E., Pratley R. E., Lee G. H., Zhang Y., Fei H., Kim S., Lallone R., Ranganathan S. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med. 1995;1:1155-1161[Medline]
39. Malmstrom R., Taskinen M. R., Karonen S. L., Yki-Jarvinen H. Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM. Diabetologia 1996;39:993-996[Medline]
40. Miell J. P., Englaro P., Blum W. F. Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Horm. Metab. Res. 1996;28:704-707[Medline]
41. Montague C. T., Farooqi I. S., Whitehead J. P., Soos M. A., Rau H., Wareham N. J., Sewter C. P., Digby J. E., Mohammed S. N., Hurst J. A., Cheetham C. H., Earley A. R., Barnett A. H., Prins J. B., O’Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature (Lond.) 1997;387:903-908[Medline]
42.
Mueller W. M., Gregoire F. M., Stanhope K. L., Mobbs C. V., Mizuno T. M., Warden C. H., Stern J. S., Havel P. J. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. Endocrinology 1998;139:551-558
43.
Orban Z., Remaley A. T., Sampson M., Trajanoski Z., Chrousos G. P. The differential effect of food intake and beta-adrenergic stimulation on adipose-derived hormones and cytokines in man. J. Clin. Endocrinol. Metab. 1999;84:2126-2133
44.
Papaspyrou-Rao S., Schneider S. H., Petersen R. N., Fried S. K. Dexamethasone increases leptin expression in humans in vivo. J. Clin. Endocrinol. Metab. 1997;82:1635-1637
45. Pratley R. E., Nicolson M., Bogardus C., Ravussin E. Effects of acute hyperinsulinemia on plasma leptin concentrations in insulin-sensitive and insulin-resistant Pima Indians. J. Clin. Endocrinol. Metab. 1996;81:4418-4421[Abstract]
46. Ricci M. R., Fried S. K. Isoproterenol decreases leptin expression in adipose tissue of obese humans. Obes. Res. 1999;7:233-240[Medline]
47. Ricci M. R., Fried S. K., Mittleman K. D. Acute cold exposure decreases plasma leptin in women. Metabolism 2000;49:421-423[Medline]
48.
Rosenbaum M., Nicolson M., Hirsch J., Murphy E., Chu F., Leibel R. L. Effects of weight change on plasma leptin concentrations and energy expenditure. J. Clin. Endocrinol. Metab. 1997;82:3647-3654
49.
Rosmond R., Dallman M. F., Bjorntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J. Clin. Endocrinol. Metab. 1998;83:1853-1859
50.
Russell C. D., Petersen R. N., Rao S. P., Ricci M. R., Prasad A., Zhang Y., Brolin R. E., Fried S. K. Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone. Am. J. Physiol. 1998;275:E507-E515
51. Satoh N., Ogawa Y., Katsuura G., Numata Y., Tsuji T., Hayase M., Ebihara K., Masuzaki H., Hosoda K., Yoshimasa Y., Nakao K. Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion. Diabetes 1999;48:1787-1793[Abstract]
52.
Scherer P. E., Williams S., Fogliano M., Baldini G., Lodish H. F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem 1995;270:26746-26749
53. Schoeller D. A., Cella L. K., Sinha M. K., Caro J. F. Entrainment of the diurnal rhythm of plasma leptin to meal timing. J. Clin. Investig. 1997;100:1882-1887[Medline]
54. Sinha M. K., Sturis J., Ohannesian J., Magosin S., Stephens T., Heiman M. L., Polonsky K. S., Caro J. F. Ultradian oscillations of leptin secretion in humans. Biochem. Biophys. Res. Commun. 1996;228:733-738[Medline]
55. Stumvoll M., Fritsche A., Tschritter O., Lehmann R., Wahl H. G., Renn W., Haring H. Leptin levels in humans are acutely suppressed by isoproterenol despite acipimox-induced inhibition of lipolysis, but not by free fatty acids. Metabolism 2000;49:335-339[Medline]
56. Trayhurn P., Duncan J. S., Rayner D. V. Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system. Biochem. J. 1995;311:729-733
57. Utriainen T., Malmstrom R., Makimattila S., Yki-Jarvinen H. Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects. Diabetes 1996;45:1364-1366[Abstract]
58. Van Gaal L. F., Wauters M. A., Mertens I. L., Considine R. V., De Leeuw I. H. Clinical endocrinology of human leptin. Int. J. Obes. Relat. Metab. Disord. 1999;23(suppl. 1):29-36
59. Van Harmelen V., Reynisdottir S., Eriksson P., Thorne A., Hoffstedt J., Lonnqvist F., Arner P. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998;47:913-917[Abstract]
60. Wabitsch M., Jensen P. B., Blum W. F., Christoffersen C. T., Englaro P., Heinze E., Rascher W., Teller W., Tornqvist H., Hauner H. Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 1996;45:1435-1438[Abstract]
61. Wang J., Liu R., Hawkins M., Barzilai N., Rossetti L. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature (Lond.) 1998;393:684-688[Medline]
62. Zakrzewska K. E., Cusin I., Sainsbury A., Rohner-Jeanrenaud F., Jeanrenaud B. Glucocorticoids as counterregulatory hormones of leptin: toward an understanding of leptin resistance. Diabetes 1997;46:717-719[Abstract]
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