Biomedical subjects

R V Considine

Publications and source records attributed to R V Considine.

At least 19 recordsLinked to original sources

PubMed2004

Expression of the thermogenic nuclear hormone receptor coactivator PGC-1alpha is reduced in the adipose tissue of morbidly obese subjects.

Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) is an accessory protein which can potentiate the transcriptional activation function of many nuclear hormone receptors. Its tissue distribution and physiological studies suggest that its principal in vivo roles are to promote cold-induced thermogenesis, mitochondrial biogenesis, hepatic gluconeogenesis, and fatty acid beta-oxidation. It is expressed in the white adipose tissue of both humans and rodents, and in rodents it has been suggested to mediate in part the leptin-induced conversion of white adipocytes from fat storing to fat oxidising cells. In this study, quantitative real-time PCR has been used in human tissue to demonstrate that (1) PGC1alpha mRNA levels in subcutaneous fat are three-fold lower in morbidly obese than in slim subjects; (2) there are no differences in PGC1alpha mRNA between omental and subcutaneous mature adipocytes; (3) there is a robust induction of PGC1alpha expression during subcutaneous human preadipocyte differentiation ex vivo. Whether low PGC1alpha expression is a prelude to the development of obesity, or a consequence of that obesity, attempts to upregulate endogenous white adipose tissue expression may prove a valuable new avenue to explore in obesity therapy.

Adipocytes↗

PubMed2003

Leptin levels in type 2 diabetes: associations with measures of insulin resistance and insulin secretion.

Interactions between leptin and insulin have been shown previously, in vitro and in vivo. In this study, we evaluate the associations of leptin levels with insulin secretion and insulin sensitivity in type 2 diabetes. Fasting leptin levels, HbA 1c, glucose, insulin, C-peptide, intact and des-31,32-proinsulin were measured in 100 non-insulin-treated type 2 diabetic patients. Glucose, insulin and C-peptide were measured 2 hours after an oral glucose load. Insulin resistance and beta-cell function were calculated using HOMA. Leptin levels were found to be associated with all measures of beta-cell secretion: with fasting and 2 hours insulin and C-peptide, with intact and des-31,32-proinsulin concentrations, and with beta-cell secretion estimated with HOMA. This association was independent of age and body fat in women, but in men, associations with insulin and C-peptide weakened after controlling for fat mass, whereas those with intact and des-31,32-proinsulin disappeared. Fasting insulin and C-peptide levels were also significant in multiple regression analyses, besides gender and fat mass. Insulin resistance, as assessed by HOMA, was strongly correlated with leptin, also after correction for age and fat mass in both genders. We conclude that, besides fat mass and gender - the main determinants for leptin levels in type 2 diabetic subjects as in healthy subjects - insulin secretion and the degree of insulin resistance also seem to contribute significantly to leptin levels.

Adipose Tissue↗

PubMed2002

Serum leptin responses after acute resistance exercise protocols.

This study examined the acute effects of maximum strength (MS), muscular hypertrophy (MH), and strength endurance (SE) resistance exercise protocols on serum leptin. Ten young lean men (age = 23 +/- 4 yr; body weight = 79.6 +/- 5.2 kg; body fat = 10.2 +/- 3.9%) participated in MS [4 sets x 5 repetitions (reps) at 88% of 1 repetition maximum (1 RM) with 3 min of rest between sets], MH (4 sets x 10 reps at 75% of 1 RM with 2 min of rest between sets), SE (4 sets x 15 reps at 60% of 1 RM with 1 min of rest between sets), and control (C) sessions. Blood samples were collected before and immediately after exercise and after 30 min of recovery. Serum leptin at 30 min of recovery exhibited similar reductions from baseline after the MS (-20 +/- 5%), MH (-20 +/- 4%), and SE (-15 +/- 6%) protocols that were comparable to fasting-induced reduction in the C session (-12 +/- 3%) (P < 0.05). Furthermore, no differences were found in serum leptin among the MS, MH, SE, and C sessions immediately after exercise and at 30 min of recovery (P > 0.05). Cortisol was higher (P < 0.05) after the MH and SE protocols than after the MS and C sessions. Glucose and growth hormone were higher (P < 0.05) after exercise in the MS, MH, and SE protocols than after the C session. In conclusion, typical resistance exercise protocols designed for development of MS, MH, and SE did not result in serum leptin changes when sampled immediately or 30 min postexercise.

Adult↗

PubMed2001

Regulation of leptin production.

Fat mass is the primary determinant of serum leptin in humans with energy intake and gender also having significant effects. Gender influences leptin production through the reproductive hormones. Glucose metabolism links food intake to leptin production and hexosamine biosynthesis appears to play a significant role in this process. Catecholamines inhibit leptin production and the sympathetic nervous system has been proposed to be the efferent arm of the leptin signal transduction pathway between adipose tissue and the central nervous system. Additional regulators of leptin production include glucocorticoids, cytokines and agonists of PPAR gamma. In addition to adipose tissue, leptin is produced in several other places including placenta, bone marrow, stomach, muscle and perhaps brain, thus increasing the number of potential regulatory roles for this hormone. Future work will be needed to fully elucidate the mechanisms regulating leptin synthesis/release in each tissue as well as its regulatory functions.

Adipose Tissue↗

PubMed2001

Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women.

OBJECTIVE: Leptin is an adipocyte-secreted hormone involved in body weight regulation, acting through the leptin receptor, localised centrally in the hypothalamus as well as peripherally, amongst others on adipose tissue. The aim of this study was to evaluate whether polymorphisms in the leptin receptor (LEPR) gene were related to obesity and body fat distribution phenotypes, such as waist and hip circumferences and the amount of visceral and subcutaneous fat. METHODS: Three known LEPR polymorphisms, Lys109Arg, Gln223Arg and Lys656Asn, were typed on genomic DNA of 280 overweight and obese women (body mass index (BMI)>25), aged 18-60 y. General linear model (GLM) analyses were performed in 198 pre- and 82 postmenopausal women, adjusting the data for age and menopausal state, plus fat mass for the fat distribution phenotypes. RESULTS: No associations were found between the LEPR polymorphisms and BMI or fat mass. In postmenopausal women, carriers of the Asn656 allele had increased hip circumference (P=0.03), total abdominal fat (P=0.03) and subcutaneous fat (P=0.04) measured by CT scan. Total abdominal fat was also higher in Gln223Gln homozygotes (P=0.04). Also in postmenopausal women, leptin levels were higher in Lys109Lys homozygotes (P=0.02). CONCLUSION: In conclusion, polymorphisms in the leptin receptor gene are associated with levels of abdominal fat in postmenopausal overweight women. Since body fat distribution variables were adjusted for fat mass, these results suggest that DNA sequence variations in the leptin receptor gene play a role in fat topography and may be involved in the predisposition to abdominal obesity.

Adipose Tissue↗

PubMed2001

Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans.

Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists appear to inhibit resistin expression in murine adipocytes, providing a possible explanation for the mode of action of this class of insulin sensitizers (2). Using a fluorescent real-time reverse transcriptase-polymerase chain reaction-based assay, we found that resistin mRNA levels in whole adipose tissue samples were increased in morbidly obese humans compared with lean control subjects. However, in freshly isolated human adipocytes, resistin mRNA levels were very low and showed no correlation with BMI. Resistin mRNA was undetectable in preadipocytes, endothelial cells, and vascular smooth muscle cells, but it was readily detectable in circulating mononuclear cells. Although exposure of human mononuclear cells to PPAR-gamma agonists markedly upregulated fatty acid-binding protein-4 expression, these agents had no effect on mononuclear cell resistin expression. Finally, resistin mRNA was undetectable in adipocytes from a severely insulin-resistant subject with a dominant-negative mutation in PPAR-gamma (3). We conclude that the recently described relationships of murine resistin/Fizz3 expression with obesity, insulin resistance, and PPAR-gamma action may not readily translate to humans. Further studies of this novel class of proteins are needed to clarify their roles in human metabolism.

Adipocytes↗

PubMed2000

Intensity of acute exercise does not affect serum leptin concentrations in young men.

PURPOSE: We examined the effects of exercise intensity on serum leptin levels. METHODS: Seven men (age = 27.0 yr; height = 178.3 cm; weight = 82.2 kg) were tested on a control (C) day and on 5 exercise days (EX). Subjects exercised (30 min) at the following intensities: 25% and 75% of the difference between the lactate threshold (LT) and rest (0.25 LT, 0.75 LT), at LT, and at 25% and 75% of the difference between LT and VO2peak (1.25 LT, 1.75 LT). RESULTS: Kcal expended during the exercise bouts ranged from 150 +/- 11 kcal (0.25 LT) to 529 +/- 45 kcal (1.75 LT), whereas exercise + 3.5 h recovery kcal ranged from 310 +/- 14 kcal (0.25 LT) to 722 +/- 51 kcal (1.75 LT). Leptin area under the curve (AUC) (Q 10-min samples) for all six conditions (C + 5 Ex) was calculated for baseline (0700-0900 h) and for exercise + recovery (0900-1300 h). Leptin AUC for baseline ranged from 243 +/- 33 to 291 +/- 56 ng x mL(-1) x min; for exercise + recovery results ranged from 424 +/- 56 to 542 +/- 99 ng x mL(-1) x min. No differences were observed among conditions within either the baseline or exercise + recovery time frames. Regression analysis confirmed positive relationships between serum leptin concentrations and percentage body fat (r = 0.94) and fat mass (r = 0.93, P < 0.01). CONCLUSION: We conclude that 30 min of acute exercise, at varying intensity of exercise and caloric expenditure, does not affect serum leptin concentrations during exercise or for the first 3.5 hours of recovery in healthy young men.

Adult↗

PubMed2000

Localization of leptin receptor-like immunoreactivity in the corticotropes, somatotropes, and gonadotropes in the ovine anterior pituitary.

Leptin is a secreted product of the adipocytes that regulates a variety of functions. The presence of the leptin receptor (LR) has been demonstrated in the endocrine and neuroendocrine tissue, but only limited information is available regarding cell-specific expression in the anterior pituitary gland. We have used double-label immunofluorescence histochemistry to study the distribution of LR-like immunoreactivity (LR-ir) in the corticotropes, somatotropes, and gonadotropes of the ovine anterior pituitary. LR-ir was found in 34% of cells in the pars distalis and 94% of the cells in the pars tuberalis. In the pars distalis, LR-ir was present in 27% of corticotropes, 69% of somatotropes, and 29% of gonadotropes. In contrast, 90% of the gonadotropes in the pars tuberalis were immunopositive for LR. There was no alteration in the number of gonadotropes containing LR-ir during the various phases of the estrous cycle (n = 3/group) in the pars distalis (luteal phase, 36%; follicular phase, 32%; and estrous phase, 32%). In conclusion, we show that, in the pars distalis, LR-ir is expressed to a greater extent in the somatotropes than in the gonadotropes or corticotropes. This is in accordance with the documented effects of leptin on pituitary GH secretion. The differential expression of LR-ir between the gonadotropes of the pars distalis and pars tuberalis probably reflects the different phenotypes of the cells in these two regions. Lower levels of LR-ir expression in gonadotropes and corticotropes of the pars distalis may suggest that leptin does not substantially influence these particular cells, at least in this species.

Adrenocorticotropic Hormone↗

PubMed2000

Hexosamines stimulate leptin production in transgenic mice.

Hexosamine flux has been shown to mediate aspects of nutrient sensing in insulin sensitive tissues and has been hypothesized to represent a satiety signal that results in shunting of fuel toward storage as fat. It has been recently reported that in vitro treatment of fat and muscle cells with hexosamines and acute glucosamine infusion in intact rats stimulate leptin secretion. In order to investigate the effects of chronic, physiologic increases in hexosamine flux on leptin we have examined leptin mRNA and serum leptin in mice overexpressing the rate-limiting enzyme for hexosamine synthesis, GFA, in muscle and fat. Increased levels of UDP-N-acetylglucosamine, the principal end-product of the hexosamine pathway were seen in transgenic fat, consistent with the overexpression of GFA. After overnight fasting, the transgenic mice were hyperleptinemic compared to littermate controls (4.5+/-0.5 ng/ml in transgenic, 2.8+/-0.2 in control, p = 0.005) despite equal body weights. In the random-fed state, the leptin levels of control mice increased to 4.1+/-0.5 ng/ml (p = 0.01) whereas the leptin levels in the transgenics did not increase any further (3.7+/-0.4 ng/ml). Leptin mRNA levels were also increased in transgenic fat (2.7+/-0.6 in transgenic compared to 0.8+/-0.2 in control, arbitrary units normalized to actin, p < 0.007). Despite increased leptin, the transgenic animals did not have lower body fat content. We conclude that hexosamine flux in fat regulates leptin synthesis and secretion.

Adipose Tissue↗

PubMed2000

Hexosamines regulate leptin production in human subcutaneous adipocytes.

The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells "sense" nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of leptin production by hexosamines in human adipocytes. Adipose tissue UDP-N-acetylglucosamine, an end product of hexosamine biosynthesis, was elevated 3.2-fold, and ob messenger ribonucleic acid was elevated 2-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3+/-12.0 kg/m2; age, 31+/-5 yr] subjects compared to 14 lean (BMI, 23.4+/-1.6 kg/m2; age, 33+/-11 yr) subjects. Serum leptin was increased 2.7-fold in the obese subjects. A significant positive relationship was found between adipose tissue UDP-N-acetylglucosamine and BMI (Spearman correlation = 0.576; P = 0.0007) and between UDP-N-acetylglucosamine and serum leptin (Spearman correlation = 0.4650; P = 0.0145). Treatment of isolated sc adipocytes with 1 mmol/L glucosamine, an intermediate product in UDP-N-acetylglucosamine biosynthesis, increased leptin release 21.4+/-17.6% (mean +/- SD) over control (P = 0.0365) and 74.5+/-82.8% over control (P = 0.0271) in adipocytes from lean (BMI, 23.2+/-1.6 kg/m2; n = 6) and obese (BMI, 55.4+/-13.0 kg/m2,; n = 9) subjects, respectively, by 48 h of culture. Inhibition of UDP-N-acetylglucosamine biosynthesis with 6-diazo-5-oxo-norleucine reduced glucose-stimulated leptin release from cultured adipocytes 21.8+/-32.4% (P = 0.0395; n = 12) and ob gene expression 19.9+/-18.9% (P = 0.0208; n = 8) by 48 h of treatment. These findings suggest that hexosamine biosynthesis regulates leptin production in human adipose tissue.

Adipocytes↗

PubMed2000

Tumor necrosis factor-alpha inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans.

This study was undertaken to examine the regulation of leptin production from human adipocytes by tumor necrosis factor-alpha (TNFalpha). Adipocytes were isolated from adipose tissue obtained during bariatric surgical procedures (17 women and 3 men; body mass index, 52.5 +/- 2.4 kg/m2; age, 40 +/- 3 yr) and cultured in suspension. Leptin release from sc adipocytes was inhibited 17.7 +/- 5.2% (P < 0.01), 21.6 +/- 4.3% (P < 0.005), and 37.1 +/- 7.2% (P < 0.05) by 1, 10, and 100 ng/mL TNFalpha, respectively, after 48 h in culture. At 100 ng/mL, significant inhibition of leptin release (25.8 +/- 9.7%; P < 0.05) was detected by 24 h. TNFalpha (10 ng/mL) had no effect on dexamethasone (0.1 micromol/L)-stimulated leptin production in sc adipocytes. In omental adipocytes TNFalpha inhibited leptin release 21.0 +/- 9.6% and 40.8 +/- 6.3% at 10 and 100 ng/mL by 48 h (P < 0.05). Significant inhibition ofleptin release from omental adipocytes was observed at 24 h with 100 ng/mL TNFalpha (P < 0.05). Anti-TNFalpha antibody completely blocked TNFalpha inhibition of leptin release. The ob messenger ribonucleic acid was significantly reduced (23.6 +/- 5.9%) after 48 h of TNFalpha (100 ng/mL) treatment (P < 0.025). TNFalpha had no effect on glucose uptake or lactate production in sc and omental adipocytes. The data suggest that the direct paracrine effect of adipose-derived TNFalpha is inhibition of leptin production.

Adipocytes↗

PubMed2000

Leptin production in adipocytes from morbidly obese subjects: stimulation by dexamethasone, inhibition with troglitazone, and influence of gender.

This study examined the regulation of leptin production by dexamethasone and troglitazone. Subcutaneous and omental adipose tissue was obtained during bariatric surgical procedures (30 women and 16 men; body mass index, 52.5 +/- 1.7 kg/m2, age, 39 +/- 2 yr), and adipocytes were cultured in suspension. Subcutaneous adipocytes from females released significantly more leptin than did omental cells from the same subject (P < 0.05), but basal leptin release was not different in adipocytes from these depots in males. Dexamethasone (0.1 micromol/L) significantly increased leptin release within 24 h from sc (135 +/- 13% of control) and omental (227 +/- 53%) adipocytes of females, but not males. Dexamethasone-stimulated leptin production at 48 h was significantly greater in the omental adipocytes of females (398 +/- 64% of control) than in sc adipocytes of females (207 +/- 21%) or the omental (211 +/- 33%) and sc (180 +/- 23%) adipocytes of males. Troglitazone (10 micromol/L; 48 h) significantly inhibited dexamethasone-stimulated leptin release in sc (57 +/- 10.7% inhibition) and omental adipocytes (134 +/- 26% inhibition). There was no gender-related difference in the effect of troglitazone to inhibit dexamethasone-stimulated leptin release. Troglitazone significantly inhibited basal leptin production from omental adipocytes by 15.0 +/- 5.2%. The effect of dexamethasone and troglitazone to regulate leptin release was mediated through changes in ob gene expression, but did not involve changes in glucose uptake or metabolism to lactate. The data suggest that adipocytes from females are more responsive to the stimulatory effect of dexamethasone in vitro than are adipocytes from males. If adipocytes from females are more responsive to relevant in vivo stimuli for leptin secretion such as insulin or glucose, this could contribute to the gender difference in serum leptin. The data also suggest that leptin release from omental adipocytes may be more responsive to hormonal and nutrient regulation in vivo than are sc adipocytes.

Adipocytes↗

PubMed2000

Human leptin: from an adipocyte hormone to an endocrine mediator.

Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic-pituitary-adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic-pituitary-gonadal axis and on insulin metabolism, but also on the hypothalamic-pituitary-adrenal, thyroid and GH axes. Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.

Adipocytes↗

PubMed1999

Weight loss and leptin changes in individuals with type 2 diabetes.

OBJECTIVE: To identify variables associated with leptin change in subjects with type 2 diabetes after 3 weeks and 20 weeks of weight loss. RESEARCH METHODS AND PROCEDURES: Subjects with type 2 diabetes treated with diet or sulfonylureas (n = 54) were enrolled in a 20-week behavioral weight control program. Sulfonylureas were stopped > or =2 weeks before study entry. Seven subjects who restarted sulfonylureas after week 3 had their data analyzed separately after this point. RESULTS: Leptin, fasting plasma glucose, and insulin levels were measured at baseline and at 3, 10, and 20 weeks. After 3 weeks, subjects lost 2.7+/-2.0 kg (p<0.001), and had significant decreases in leptin (5.2+/-7.0 ng/mL, p<0.001), fasting plasma glucose (1.8+/-1.8 mmol/L, p<0.001), and insulin (23+/-60 pmol/L, p<0.03). Between week 3 and week 20, subjects lost an additional 6.3+/-4.4 kg (p<0.001), but had no further changes in leptin. The primary determinants of leptin change at all time-points were weight loss and initial leptin level. Changes in insulin were not related to changes in leptin after controlling for the effects of weight loss. At week 20, more recent weight loss (week 10 to week 20) was as strong a predictor of overall change in leptin as overall weight loss (baseline to 20 week). Subjects who restarted sulfonylureas had an increase in both leptin levels (+1.9+/-9.0 ng/mL, p<0.05) and insulin levels (+23+/-65 pmol/L, p<0.05), despite significant overall weight loss (-7.4+/-4.0 kg, p<0.01). Initial changes in leptin (0 weeks to 3 weeks) did not affect subsequent ability to lose weight. DISCUSSION: Both short- and long-term changes in weight had an effect on leptin changes in individuals with type 2 diabetes. Although physiological insulin changes did not independently influence changes in leptin concentration with weight loss, increases in insulin levels with sulfonylurea therapy were associated with increases in leptin levels despite weight loss.

Adult↗

PubMed1999

Clinical endocrinology of human leptin.

Since the discovery of leptin, a boom of scientific knowledge became available about the OB-protein gene and its role and significance in weight regulation. Both from animal and human research data, serum leptin can probably be considered as one of the best biological markers to reflect total body fat, and this finding is true over a wide range of body mass indexes (BMIs) and in different pathologies: in normal weight, anorexic and obese subjects; in non insulin-dependent diabetes mellitus (NIDDM) patients, PCO women, Prader-Willi children and subjects with hypogonadism and growth hormone deficiency. Gender differences clearly exist, probably related to sex hormone differences, and from fat distribution studies it could be shown that subcutaneous fat is much more related to serum leptin concentrations than visceral fat: also leptin messenger-RNA (m-RNA) expression is significantly higher in subcutaneous fat from human obese subjects. Leptin is not only correlated to a series of endocrine parameters such as insulin, insulin-like growth factor, (IGF) and SHBG, it seems involved as a mediator in some endocrine mechanisms (onset of puberty, insulin secretion, etc) as well. Weight loss will reduce human leptin concentrations, whereas the administration of human recombinant leptin seems to show only limited effects.

Adipose Tissue↗

PubMed1999

Serum leptin levels in women throughout pregnancy and the postpartum period and in women suffering spontaneous abortion.

OBJECTIVE: In pregnancy, important changes occur in the body weight of the mother, caused by sodium and water retention and by an increase in body fat tissue, but the mechanisms that regulate maternal and foetal changes in fat mass are poorly understood. Leptin is a hormone produced by adipocytes in order to regulate food intake and energy expenditure at the hypothalamic level in man. In order to verify whether leptin participates in the changes in body composition during pregnancy and postpartum, 630 healthy women were studied at specific time periods and leptin and auxological parameters were determined. DESIGN: A cross-sectional study in which leptin levels were measured in women at specific time periods related to pregnancy. Each woman was assessed only once. PATIENTS: 630 women participated in the study, and were divided into categories as follows: Group A, 29 internal controls, with no previous or current pregnancy; Group B, 73 women in the first trimester of pregnancy; Group C, 60 women in the 24 h before delivery; Group D, 212 women in the 24 h postpartum; Group E, 93 women in the eightH postpartum week (2 months group); Group F, 71 women in the sixteenth postpartum week (4 months group); Group G, 20 women in the sixth month postpartum; Group H, 23 women one year postpartum; Group I, 20 women two years postpartum; finally Group J, of 29 women who had suffered spontaneous abortion in the first trimester of pregnancy and were studied in the 24 h after the stillborn delivery. MEASUREMENTS: Serum leptin levels were measured in duplicate by radioimmunoassay using commercial kits. Height and weight was measured and BMI (kg/m2) calculated. RESULTS: Compared with serum leptin in the control group (11.7 +/- 1.0 micrograms/l), a non significant (NS) increase was observed in the first trimester of pregnancy (14.3 +/- 1.4 micrograms/l), with no parallel changes in body weight. A reduction in leptin occurred in the 24 h after delivery (9.4 +/- 1.4 micrograms/l, P = 0.02). After delivery a progressive increase in leptin concentrations was observed, 13.3 +/- 1.5 micrograms/l at two months (NS) and 17.4 +/- 2.6 micrograms/l at four months (P = 0.035 vs controls). Afterwards leptin values decreased towards normal values at 6, 12 and 24 months after delivery 14.4 +/- 1.8 micrograms/l; 12.9 +/- 1.6 micrograms/l; and 10.1 +/- 1.1 micrograms/l respectively (all NS). With the exception of the postpartum group, a significant correlation was observed between leptin concentrations and body weight or BMI in each group of women studied. In the women who suffered spontaneous abortion in the first trimester of pregnancy a reduction in leptin levels occurred (8.8 +/- 1.0 micrograms/l, P = 0.001 vs first trimester group). CONCLUSION: Serum leptin concentrations rose slightly during pregnancy, fell following delivery and subsequently increased during the first six months postpartum. These variations were unrelated to changes in body composition, and may be responsible for the postpartum weight gain observed in some women. Abnormally low serum leptin levels were observed in women suffering spontaneous abortion in the first trimester of pregnancy.

Abortion, Spontaneous↗

PubMed1999

Serum leptin during recovery following maximal incremental and prolonged exercise.

This study investigated the delayed circulating leptin response to maximal and prolonged treadmill exercise. Six healthy untrained males performed three sessions after an overnight fast: control, maximal exercise, and prolonged exercise at 50% of maximal oxygen consumption. Blood samples were collected prior to exercise, at the end of exercise, and at 60, 120, 180, and 240 min following exercise and control sessions. Blood samples were analyzed for serum leptin, insulin, glucose, free fatty acids, and glycerol. Hemoglobin and hematocrit were measured to correct for plasma volume changes. Resting energy expenditure (REE) and body fat (BF) were also assessed. Immediately at the end of maximal and prolonged exercise, and during the 4 hours of recovery, serum leptin levels did not change significantly compared to their respective baseline values. At 240 min of recovery serum leptin decreased 7% and 9% (p>0.05) from the baseline in the maximal and prolonged sessions, respectively. In the control experiment serum leptin decreased 27% from the baseline at 240 min of the recovery (p < 0.05). No significant differences were found in leptin values between the control and exercise sessions. Control serum leptin was positively correlated (p < 0.05) to BF (r = 0.88) and glucose (r=0.96), and negatively correlated to REE (r= -0.81). In conclusion, maximal or prolonged exercise do not appear to have an influence on circulating serum leptin in the delayed (4 hr) post exercise recovery period.

Adult↗

PubMed1999

Leptin secretion in Cushing's syndrome: preservation of diurnal rhythm and absent response to corticotropin-releasing hormone.

The normal inverse relationship between leptin and cortisol is lost in chronic hypercortisolism. We studied this apparent dysregulation in patients with Cushing's syndrome to investigate 1) the effect of chronic hypercortisolemia on the circadian rhythm of leptin secretion, 2) the response of leptin after administration of CRH, and 3) the short term effect of curative surgery on leptin. The preoperative morning leptin concentration was 54.2 +/- 8.1 ng/mL, and the nighttime value was 68.6 +/- 9.8 ng/mL, reflecting a mean rise of 32.8 +/- 7.6%, similar to the nocturnal increase observed in normal subjects. By contrast, cortisol's diurnal variation (21.8 +/- 1.7 vs. 16.9 +/- 1.1 mg/dL) was blunted. In women, but not men, body mass index correlated with leptin (P = 0.001). Preoperative ACTH and cortisol (both P < 0.0001), but not leptin levels increased after CRH. Ten days after surgery, basal cortisol values were subnormal (1.1 +/- 0.6 mg/dL), but leptin levels remained unchanged and did not increase after CRH. Body mass index and insulin also remained unchanged. Insulin, but not age, urinary free cortisol, or plasma cortisol correlated with leptin (P < 0.05). In summary, patients with Cushing's syndrome have moderately elevated leptin levels that maintain an intact circadian rhythm but do not respond to acute or subacute alterations of cortisol.

Adenoma↗