| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
The Department of Medicine (M.F.S., M.G.R.-G., A.K., A.S., R.M., S.D.J., R.B.), University of Southern California Medical School, Los Angeles, California 90033; and Joslin Diabetes Center (G.M.S.), Boston, Massachusetts 02215
Address all correspondence and requests for reprints to: Mohammed F. Saad, M.D., Division of Endocrinology and Diabetes, University of Southern California Medical School, 1200 North State Street, Unit I, P.O. Box 710, Los Angeles, California 90033. E-mail: saad{at}hsc.usc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This study included 31 healthy subjects (17 men, 14 women),
36 ± 2 (mean ± SEM) yr old (range 18–55) with
a body mass index (BMI) of 27.5 ± 1.0 kg/m2 (range
19.9–40.7). None was taking any medications. Obesity was defined by a
BMI > 27 kg/m2 (26). Thus, subjects were divided into
4 groups by gender and obesity (Table 1
).
The study was approved by the Institutional Review Board of the
University of Southern California, and all subjects gave informed
consent.
|
Subjects had an oral glucose tolerance test, with a 75-g glucose, to rule out diabetes. Body composition was determined by underwater weighing (27). Subjects were subsequently admitted to the Clinical Research Center for 3 days and were kept on a weight-maintenance diet. On the third day and after a 10- to 12-h overnight fast, an iv catheter was placed at 0500 h. Blood was collected for determination of plasma glucose, insulin, and leptin concentrations every 20 min for 24 h, starting at 0600 h. Breakfast, lunch, and dinner were served at 0800 h, 1300 h, and 1800 h, respectively. The caloric distribution was 20% for breakfast, 40% for lunch, and 40% for dinner. Only water was allowed between meals. Subjects did not nap or sleep until 2300 h, when lights and television were turned off.
Biochemical analyses
Plasma glucose was determined by the glucose oxidase method. Insulin and leptin were determined by RIA with reagents from Linco Research (St. Louis, MO), with detection limits of 12 pmol/L and 0.5 ng/mL, respectively. The interassay coefficients of variation were 6–8 and 5–7% for insulin and leptin assays, respectively. All samples from a single participant were measured in triplicate in the same assay. Plasma testosterone and estradiol were measured in fasting samples (at 0800 h), in duplicate, with kits from Diagnostic Products Corporation (Los Angeles, CA).
Data analysis
The 24-h leptin profiles were analyzed for peak (single highest) and nadir (single lowest) values and for several indices, for the extent of the diurnal change. These included 24-h excursion (peak-nadir/24 h mean) expressed as a percent, the coefficient of variation around the 24-h mean (24-h CV), and the night/day ratio (ratio of average leptin levels during the night (2000–0540 h) to day (0600–1940 h). In addition, spectral and pulse analyses were performed.
Spectral analysis was done with MLAB (Civilized Software, Inc., Bethesda, MD) using a power-of-two fast Fourier transform (FFT). Fourier transform analysis is a mathematical technique that assesses the contribution of oscillations of different periodicities to total oscillatory activity in a data set (28). Because of gender- and obesity-related differences, leptin levels were first normalized by calculating percent of change at different time points in relation to the 24-h mean. The amplitude of the oscillations (square root of the spectrum) and phase spectrum were calculated from FFT of the normalized data. FFT results also were used to predict a theoretical time course using 1, 2, and 3 principal harmonics (equivalent to cosinar analysis with periods of 24, 12, and 8 h). Residuals (data - FFT predicted curve) were subjected to autocorrelation analysis; spectral components that did not reduce the oscillatory nature of the autocorrelation function were not considered significant. Time profiles consistent with a diurnal rhythm (period = 24 h) and a diurnal plus a 12-h component were identified. Estimated time profiles of higher-order spectral components were not significant, and the R2 values for fits involving the first two cosines were 86 ± 2%. The estimated phase was used to calculate the time-to-peak value of the first two cosine components (the peak of the diurnal and the first peak of the 12-h components).
Pulse analysis was performed with the pulse-identification program, ULTRA (29, 30). The general principle of this program is the elimination of all peaks of plasma concentration for which either the increment (difference between peak value and the preceding nadir) or the decrement (difference between peak value and the next nadir) does not exceed a certain threshold related to measurement error. Peaks that do not meet threshold criteria are eliminated from the data set using an iterative process, leaving a clean series in which all remaining peaks are assumed to represent significant pulses. The intraassay coefficient of variation of leptin assay was less than 5%, and therefore, the threshold for pulse detection was set at 10%. Each pulse was characterized in terms of total duration and absolute (difference between levels at the peak and at the preceding trough) and relative (percent increase above the trough) increments.
Statistical analyses
Data are expressed as means ± SEM or as means with 95% confidence interval. Insulin and leptin concentrations were log-transformed to normalize the distribution. Statistical analyses were performed with programs of SPSS, Inc., Chicago, IL (31). Two-way ANOVA was used to evaluate the effects of gender and obesity on different variables. Linear regression and/or Pearson product moment correlations (unless otherwise specified) were used to evaluate the relations among different variables. Multiple linear regression, with a backward-stepwise procedure, was used to define the variables most predictive of 24-h leptin concentration and of the amplitudes of the two spectral components.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
), leptin
profiles were higher in lean and obese women than in their male
counterparts (Fig. 2). Mean 24-h plasma
leptin concentration and the 24-h area under the curve (AUC) correlated
strongly with BMI, percent body fat, and fat mass in men and women
(Table 2). Nevertheless, women had higher
24-h mean leptin and AUC at any BMI, percent body fat, or fat mass
(Fig. 3). Leptin AUC correlated with the
waist/hip ratio in men but not in women (Table 2). After adjusting for
fat mass, the relation was significant in neither men nor women. Leptin
and insulin AUC were correlated in men (r = 0.65,
P = 0.005) and women (r = 0.54, P
= 0.056), but these relations became insignificant after controlling
for adiposity. Leptin AUC was not significantly correlated to plasma
testosterone or estradiol in men (r = -0.33, -0.28 respectively)
or women (r = 0.38, 0.03). Multiple regression showed that fat
mass and gender explained 86% of the variance in 24-h leptin AUC
(Table 3).
|
|
|
|
|
).
|
). Gender had no effect on the relative
amplitude of the 12-h component, which was higher in lean individuals
(Table 4
). The peak of the diurnal component occurred between 2140 and
0140 (median 0020). The first peak of the 12-h component occurred
between 1240 and 2240 (median 1400) and the second peak, 12 h
later, i.e. between 0040 and 1040 (median 0200). Neither
gender nor obesity had an effect on the time of the peak of either
component. Multiple regression showed that 24-h insulin AUC, female
sex, and age were negative determinants of the relative amplitude of
the diurnal component, explaining 31% of its variance (Table 5). The same type of analysis indicated
that age was a weak negative determinant of the relative amplitude of
the 12-h component, explaining 8% of its variance (P =
0.055); none of the other variables were significant.
|
|
). Pulses
were less frequent in obese than in lean subjects, but no sex
differences were detected (Table 4). Pulse frequency was inversely
related to fat mass and the 24-h insulin AUC (Spearman’s r =
-0.54 and -0.37, respectively; P < 0.05 for each).
Absolute pulse increments were higher in women than men and in obese
individuals. Neither gender nor obesity had an effect, however, on the
relative increments (Table 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Diurnal leptin rhythmicity does not seem to be controlled by the endogenous circadian clock. Schoeller et al. (32) have recently shown that day/night reversal produced a rapid phase shift that was dissociated from the change in cortisol. Meal time and insulin apparently play a major role, because delaying meals for 6.5 h caused a 4–7 h shift in nadir and peak leptin levels (32). Other hormones that show diurnal changes and can influence plasma leptin, such as neuropeptide Y (33), corticosteroids (34), and catecholamines (35), could also modulate its diurnal rhythm. In addition, circulating leptin is bound to one or more binding proteins (36, 37) that may modulate its plasma pattern.
Insulin could be the major determinant of leptin secretory pattern.
Although several studies showed that insulin infusions for 2–10 h had
no effect on plasma leptin concentration (38, 39, 40, 41, 42), our preliminary data
show that insulin, in concentrations well within the physiologic range,
could increase plasma leptin by approximately 50% and that such an
effect takes 2–3 h to become evident. In addition, other studies
showed that infusion of insulin or glucose could increase plasma leptin
concentration in 4–6 h (43, 44, 45). It is plausible, therefore, that
repeated daytime postprandial insulin release could induce increases in
leptinemia that become apparent in the afternoon and during the night.
Conversely, the nocturnal postabsorptive diminution in insulinemia
could cause a decline in leptinemia that becomes manifest in the early
morning hours. Thus, insulinemia could influence the magnitude of the
diurnal leptin excursion (Table 5). Meanwhile, postprandial insulin
excursions could cause fluctuations in plasma leptin, which are
reflected as episodic pulsations. This is supported by the occurrence
of prominent leptin pulsatility 2–3 h after meals (Fig. 5). Moreover,
an insulin infusion that kept its level constantly elevated at twice
that of basal completely eliminated pulsatility for 9 h
(unpublished observations). Thus, the insulin secretory pattern seems
to modulate the 24-h leptin profile.
Hyper and hypoinsulinemia could perturb leptin rhythmicity. In obesity, the fasting and postprandial hyperinsulinemia could continuously up-regulate leptin production and thereby buffer the daytime decline and limit the fluctuations in its plasma concentration, resulting in decreased diurnal excursion and dampened pulsatility. Our data show that 24-h insulin AUC correlated negatively with leptin’s diurnal rhythm amplitude and its pulse frequency (Spearman r = -0.34 and -0.37, respectively; P < 0.05 for each). Furthermore, hyperinsulinemia usually reflects insulin resistance, which can diminish the stimulatory effect of postprandial insulin release on leptin production and consequently decrease the diurnal rhythm amplitude. Hypo-insulinemia also could lead to the same result but through down-regulating leptin production. Laughlin and Yen (24) showed that the diurnal variations in leptin were absent in amenorrheic women athletes with low postprandial insulin excursions. The pathophysiological significance of impaired leptin secretory pattern in hyper and hypoinsulinemic states is unknown but merits further evaluation.
Absolute plasma leptin levels were higher in the obese, who could be leptin resistant because of decreased cerebrospinal transport (15, 16) or defective postreceptor signaling (17). Blunted relative diurnal excursions and dampened pulsatility also could contribute to leptin resistance in obesity. Although the effectiveness of pulsatile vs. steadily infused leptin has not been evaluated, continuous hormone delivery can produce a weaker effect or induce resistance. Conversely, pulsatile hormonal stimuli seem to maintain receptor sensitivity and enhance tissue responsiveness (46). For example, pulsatile insulin (47) and glucagon (48) administration has a greater effect on glucose metabolism, whereas continuous delivery of GnRH desensitizes the pituitary to its actions (49). It is conceivable, therefore, that the diurnal and pulsatile changes in plasma leptin improve its transport across the blood-brain barrier or maintain end organ sensitivity. Hence, abnormal leptin rhythmicity could play a role in leptin resistance and, consequently, contribute to the development or worsening of obesity.
We (13) and others (10, 11, 12) have described sexual dimorphism in fasting plasma leptin concentrations. The current report extends these observations and shows sexual dimorphism not only in the 24-h leptin profile but also in the relative amplitude of its diurnal rhythm. The mechanism of this sexual dimorphism is unclear. Sex hormones do not seem to play a major role, because the sex difference exists in neonates (50) and young prepubertal children (51). Nevertheless, androgens might account for some of the difference, because testosterone was found to decrease leptin level in hypogonadal men (52) and ob expression in vitro in adipocytes (53). Differences in fat distribution may play a role. Two studies showed that ob messenger RNA (mRNA) expression is higher in sc than in intraabdominal adipose tissue (54, 55). Thus, central (visceral) android adipose tissue may produce less leptin than peripheral (sc) gynecoid fat, accounting for the differences between men and women. Nevertheless, female adipose tissue, whether sc or visceral, was found to have 2- to 3-fold higher leptin mRNA expression than in men (55, 56). Moreover, this study and others found no significant association between fat distribution and leptin, independent of total adiposity (13, 57, 58, 59, 60). Taken together, these data indicate that differences in body fat distribution and, consequently, the amount of sc fat could contribute to, but cannot completely explain, the higher leptin levels in women.
A further possibility is a sex difference in the hypothalamic regulation of leptin production. Sainsbury et al. (33) showed that intracerebroventricular administration of neuropeptide increased ob gene expression in adipose tissue of normal rats. Sexual dimorphism characterizes several hypothalamic nuclei (61), as well as neuropeptide gene expression and secretion (62). Finally, female adipose tissue is more sensitive to insulin (63), which can lead to chronic up-regulation of leptin production with subsequent blunting of diurnal rhythmicity. The significance of the sexual dimorphism in leptin concentration and rhythmicity is unclear, but several studies suggested that leptin serves as a metabolic signal to the hypothalamic centers involved in the coordination of the reproductive axis (18, 19, 20, 21, 22).
In conclusion, plasma leptin shows diurnal and ultradian rhythmicity, which is modulated by fat mass, gender, and insulinemia. Obesity is associated not only with higher absolute leptin levels but also with blunted relative diurnal excursions and dampened pulsatility. Abnormal leptin rhythmicity may contribute to leptin resistance thought to occur in obesity. Women have higher absolute leptin levels and lower relative diurnal amplitude than men at any fat mass. The significance of the sexual dimorphism in leptin is unclear, but leptin may act as a metabolic signal to the reproductive axis.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received July 11, 1997.
Revised September 16, 1997.
Revised October 3, 1997.
Accepted October 14, 1997.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  A. Sood, C. Qualls, J. Seagrave, C. Stidley, T. Archibeque, M. Berwick, and M. Schuyler Effect of Specific Allergen Inhalation on Serum Adiponectin in Human Asthma Chest, February 1, 2009; 135(2): 287 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Vorona Sleep, Sleep Disorders, and the Endocrine System ACCP Sleep Med Brd Rev, January 1, 2009; 4(0): 163 - 184. [Full Text] [PDF]
|
|
|
|
 |
|
 A. A Venner, P. K Doyle-Baker, M. E Lyon, and T. S Fung A meta-analysis of leptin reference ranges in the healthy paediatric prepubertal population Ann Clin Biochem, January 1, 2009; 46(1): 65 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L Stanhope, S. C Griffen, B. R Bair, M. M Swarbrick, N. L Keim, and P. J Havel Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1194 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L Downs and H. F Urbanski Aging-related sex-dependent loss of the circulating leptin 24-h rhythm in the rhesus monkey. J. Endocrinol., July 1, 2006; 190(1): 117 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Laferrere, C. Abraham, M. Awad, S. Jean-Baptiste, A. B. Hart, P. Garcia-Lorda, P. Kokkoris, and C. D. Russell Inhibiting Endogenous Cortisol Blunts the Meal-Entrained Rise in Serum Leptin J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2232 - 2238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Griffen, K. Oostema, K. L. Stanhope, J. Graham, D. M. Styne, N. Glaser, D. E. Cummings, M. H. Connors, and P. J. Havel Administration of Lispro Insulin with Meals Improves Glycemic Control, Increases Circulating Leptin, and Suppresses Ghrelin, Compared with Regular/NPH Insulin in Female Patients with Type 1 Diabetes J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 485 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Berggren, M. W. Hulver, and J. A. Houmard Fat as an endocrine organ: influence of exercise J Appl Physiol, August 1, 2005; 99(2): 757 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Shea, M. F. Hilton, C. Orlova, R. T. Ayers, and C. S. Mantzoros Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2537 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Buff, C. D. Morrison, V. K. Ganjam, and D. H. Keisler Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse J Anim Sci, May 1, 2005; 83(5): 1023 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. CALISSENDORFF, K. BRISMAR, and S. ROJDMARK IS DECREASED LEPTIN SECRETION AFTER ALCOHOL INGESTION CATECHOLAMINE-MEDIATED? Alcohol Alcohol., July 1, 2004; 39(4): 281 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Koutkia, B. Canavan, J. Breu, M. L Johnson, A. Depaoli, and S. K Grinspoon Relation of leptin pulse dynamics to fat distribution in HIV-infected patients Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1103 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Calvani, A. Scarfone, L. Granato, E. V. Mora, G. Nanni, M. Castagneto, A. V. Greco, M. Manco, and G. Mingrone Restoration of Adiponectin Pulsatility in Severely Obese Subjects After Weight Loss Diabetes, April 1, 2004; 53(4): 939 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I.A. Harsch, P.C. Konturek, C. Koebnick, P.P. Kuehnlein, F.S. Fuchs, S. Pour Schahin, G.H. Wiest, E.G. Hahn, T. Lohmann, and J.H. Ficker Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment Eur. Respir. J., August 1, 2003; 22(2): 251 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Koutkia, B. Canavan, M. L. Johnson, A. DePaoli, and S. Grinspoon Characterization of leptin pulse dynamics and relationship to fat mass, growth hormone, cortisol, and insulin Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E372 - E379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Kitabchi and G. E. Umpierrez Changes in Serum Leptin in Lean and Obese Subjects with Acute Hyperglycemic Crises J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2593 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gavrila, C.-K. Peng, J. L. Chan, J. E. Mietus, A. L. Goldberger, and C. S. Mantzoros Diurnal and Ultradian Dynamics of Serum Adiponectin in Healthy Men: Comparison with Leptin, Circulating Soluble Leptin Receptor, and Cortisol Patterns J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2838 - 2843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Morin-Papunen, I. Vauhkonen, R. Koivunen, A. Ruokonen, H. Martikainen, and J. S. Tapanainen Metformin Versus Ethinyl Estradiol-Cyproterone Acetate in the Treatment of Nonobese Women with Polycystic Ovary Syndrome: A Randomized Study J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 148 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S Elliott, N. L Keim, J. S Stern, K. Teff, and P. J Havel Fructose, weight gain, and the insulin resistance syndrome Am. J. Clinical Nutrition, November 1, 2002; 76(5): 911 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kilciler, M. Ozata, C. Oktenli, S.Y. Sanisoglu, E. Bolu, N. Bingol, M. Kilciler, I. C. Ozdemir, and M. Kutlu Diurnal Leptin Secretion Is Intact in Male Hypogonadotropic Hypogonadism and Is Not Influenced by Exogenous Gonadotropins J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5023 - 5029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Charmandari, M. Weise, S. R. Bornstein, G. Eisenhofer, M. F. Keil, G. P. Chrousos, and D. P. Merke Children with Classic Congenital Adrenal Hyperplasia Have Elevated Serum Leptin Concentrations and Insulin Resistance: Potential Clinical Implications J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2114 - 2120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. Herrmann, M. L. Bean, T. M. Black, P. Wang, and R. A. Coleman High Glycemic Index Carbohydrate Diet Alters the Diurnal Rhythm of Leptin But Not Insulin Concentrations Experimental Biology and Medicine, December 1, 2001; 226(11): 1037 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Ahmad, R. Guzder, A. M. Wallace, J. Thomas, W. D. Fraser, and J. P. Vora Circadian and Ultradian Rhythm and Leptin Pulsatility in Adult GH Deficiency: Effects of GH Replacement J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3499 - 3506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Cummings, J. Q. Purnell, R. S. Frayo, K. Schmidova, B. E. Wisse, and D. S. Weigle A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans Diabetes, August 1, 2001; 50(8): 1714 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Mantzoros, M. Ozata, A. B. Negrao, M. A. Suchard, M. Ziotopoulou, S. Caglayan, R. M. Elashoff, R. J. Cogswell, P. Negro, V. Liberty, et al. Synchronicity of Frequently Sampled Thyrotropin (TSH) and Leptin Concentrations in Healthy Adults and Leptin-Deficient Subjects: Evidence for Possible Partial TSH Regulation by Leptin in Humans J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3284 - 3291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Iraklianou, A. Melidonis, S. Tournis, E. Konstandelou, A. Tsatsoulis, M. Elissaf, and D. Sideris Postprandial Leptin Responses After an Oral Fat Tolerance Test: Differences in type 2 diabetes Diabetes Care, July 1, 2001; 24(7): 1299 - 1301. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kalsbeek, E. Fliers, J. A. Romijn, S. E. la Fleur, J. Wortel, O. Bakker, E. Endert, and R. M. Buijs The Suprachiasmatic Nucleus Generates the Diurnal Changes in Plasma Leptin Levels Endocrinology, June 1, 2001; 142(6): 2677 - 2685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Heptulla, A. Smitten, B. Teague, W. V. Tamborlane, Y.-Z. Ma, and S. Caprio Temporal Patterns of Circulating Leptin Levels in Lean and Obese Adolescents: Relationships to Insulin, Growth Hormone, and Free Fatty Acids Rhythmicity J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 90 - 96. [Abstract] [Full Text]
|
|
|
|
|
|
J. R. Levy, J. Lesko, R. J. Krieg Jr., R. A. Adler, and W. Stevens Leptin responses to glucose infusions in obesity-prone rats Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1088 - E1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. L. Thong, R. Hudson, R. Ross, I. Janssen, and T. E. Graham Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E307 - E313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Maccario, G. Aimaretti, G. Corneli, C. Gauna, S. Grottoli, M. Bidlingmaier, C. J. Strasburger, C. Dieguez, F. F. Casanueva, and E. Ghigo Short-term fasting abolishes the sex-related difference in GH and leptin secretion in humans Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E411 - E416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. HORLICK, M. ROSENBAUM, M. NICOLSON, L. S. LEVINE, B. FEDUN, J. WANG, R. N. PIERSON Jr., and R. L. LEIBEL Effect of Puberty on the Relationship between Circulating Leptin and Body Composition J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2509 - 2518. [Abstract] [Full Text]
|
|
|
|
|
|
A. M. Isidori, F. Strollo, M. Morè, M. Caprio, A. Aversa, C. Moretti, G. Frajese, G. Riondino, and A. Fabbri Leptin and Aging: Correlation with Endocrine Changes in Male and Female Healthy Adult Populations of Different Body Weights J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1954 - 1962. [Abstract] [Full Text]
|
|
|
|
|
|
M. M. Hagan, P. J. Havel, R. J. Seeley, S. C. Woods, N. N. Ekhator, D. G. Baker, K. K. Hill, M. D. Wortman, A. H. Miller, R. L. Gingerich, et al. Cerebrospinal Fluid and Plasma Leptin Measurements: Covariability with Dopamine and Cortisol in Fasting Humans J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3579 - 3585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Malyszko, E. Zbroch, S. Wolczynski, J. S. Malyszko, and M. Mysliwiec Leptinaemia in patients dialysed with different buffers and dialysis membranes Nephrol. Dial. Transplant., October 1, 1999; 14(10): 2527a - 2529a. [Full Text] [PDF]
|
|
|
|
|
|
J. Q. Purnell and M. H. Samuels Levels of Leptin during Hydrocortisone Infusions that Mimic Normal and Reversed Diurnal Cortisol Levels in Subjects with Adrenal Insufficiency J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3125 - 3128. [Abstract] [Full Text]
|
|
|
|
|
|
R. M. O'Doherty, P. R. Anderson, A. Z. Zhao, K. E. Bornfeldt, and C. B. Newgard Sparing effect of leptin on liver glycogen stores in rats during the fed-to-fasted transition Am J Physiol Endocrinol Metab, September 1, 1999; 277(3): E544 - E550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weise, V. Abad, R. V. Considine, L. Nieman, and K. I. Rother Leptin Secretion in Cushing's Syndrome: Preservation of Diurnal Rhythm and Absent Response to Corticotropin-Releasing Hormone J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2075 - 2079. [Abstract] [Full Text]
|
|
|
|
|
|
M. Tang-Christensen, P. J. Havel, R. R. Jacobs, P. J. Larsen, and J. L. Cameron Central Administration of Leptin Inhibits Food Intake and Activates the Sympathetic Nervous System in Rhesus Macaques J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 711 - 717. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. LeGall-Salmon, W. D. Stevens, and J. R. Levy Total Parenteral Nutrition Increases Serum Leptin Concentration in Hospitalized, Undernourished Patients JPEN J Parenter Enteral Nutr, January 1, 1999; 23(1): 38 - 42. [Abstract] [PDF]
|
|
|
|
|
|
J. Licinio, A. B. Negrão, C. Mantzoros, V. Kaklamani, M.-L. Wong, P. B. Bongiorno, P. P. Negro, A. Mulla, J. D. Veldhuis, L. Cearnal, et al. Sex Differences in Circulating Human Leptin Pulse Amplitude: Clinical Implications J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 4140 - 4147. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
