Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prader-Willi syndrome (PWS) is characterized by early childhood obesity, mental deficiency, hypogonadism, hypotonia, hypopigmentation, short stature, small hands and feet, and a characteristic face. It is the most common genetic cause of obesity and obesity is the most significant health problem for PWS patients. Ob protein (leptin), which is produced by adipose tissue, is thought to play a significant role in obesity; thus, unusually low plasma leptin levels, or relative loss of sensitivity to leptin in PWS subjects, could be an important factor in their obesity. We measured plasma leptin levels in 19 obese and 14 non-obese PWS patients [mean body mass index (BMI) 37.2 and 22.0, respectively] and compared these levels to those of 28 obese controls (mean BMI 35.5) and 16 non-obese control individuals (mean BMI 21.6). The mean plasma leptin concentration (ng/ml) for obese PWS subjects was 33.4 and 23.6 for non-obese PWS subjects. Obese control leptin was 36.2 ng/ml and non-obese control was 9.9. Among the control groups, leptin levels in females were significantly higher than those in males; the obese males and females had significantly higher leptin than their respective non-obese counterparts. These differences did not hold true for the PWS subjects. Leptin levels in obese PWS males and females were similar, and the same was true of the non-obese PWS males and females. The differences between obese and non-obese PWS subjects of both sexes were small and not significant. Comparing control groups with their PWS counterparts revealed no significant differences, with one exception: circulating plasma leptin levels in non-obese PWS males were nearly five times higher than in non-obese control males with similar BMI. This difference may reflect a more female pattern of fat distribution and hypogonadism, which are characteristic of PWS males. Leptin levels in PWS patients were not obviously correlated with the chromosome 15 finding seen in the patients.
 ...
PMID:Comparison of leptin protein levels in Prader-Willi syndrome and control individuals. 945 Aug 49

Leptin has received considerable attention as a newly recognized metabolic hormone and for its potential for therapeutic use in the treatment of human obesity. Furthermore, defects in the leptin signal pathway that result in obesity in animal models have raised the possibility of a similar etiology for obesity in humans. This review will summarize the current findings on leptin in both humans and rodents. These findings will be discussed with respect to our view of the physiology and potential for pathophysiology in leptin-mediated regulation of body weight and composition.
 ...
PMID:Leptin and the regulation of body weight. 945 23

Patients with craniopharyngioma frequently suffer from severe obesity. Leptin induces an inhibition of appetite via hypothalamic receptors. This study was undertaken to investigate whether a relationship exists between serum leptin levels and pituitary/hypothalamic lesions in craniopharyngioma patients. Serum leptin levels were evaluated by RIA in 14 patients (age 7-21 years; 7 females, 7 males) after they had undergone neurosurgical treatment for craniopharyngioma. Normal controls had a positive correlation between leptin levels and body mass index (BMI) with higher levels in the females than in the males. Significantly elevated leptin levels with respect to BMI were found in 11 craniopharyngioma patients who had been affected by a suprasellar tumour, whereas 3 patients with an intrasellar tumour had lower, almost normal serum leptin levels. Our data suggest that craniopharyngioma patients develop hypothalamic obesity because their hypothalamic structures are insensitive to endogenous leptin. The elevated serum leptin concentrations found only in patients with a suprasellar tumour may be explained by a disturbed feedback mechanism from the hypothalamic leptin receptors to the adipose tissue.
 ...
PMID:Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. 946 23

Leptin is the protein product of the ob gene, an adipocyte-specific gene, recently discovered in mice. Plasma leptin levels were determined in six normals, twenty-one subjects with impaired glucose tolerance, and forty-nine untreated NIDDM subjects. They increased with the augmentation of obesity (body mass index, BMI kg/m2) and were higher in females than in males: in BMI less than 25 kg/m2 the values of plasma leptin were 2.24 +/- 0.25 ng/ml (n=29) in males and 3.01 +/- 0.39 ng/ml (n=13) in females (P<0.054), respectively, in BMI between 25 kg/m2 and 30 kg/m2 they were 3.14 +/- 0.31 ng/ml (n=10) in males and 10.66 +/- 2.86 ng/ml (n=7) in females (P<0.0018) and in BMI higher than 30 kg/m2 their levels were 8.98 +/- 1.5 ng/ml (n=11) and 11.74 +/- 2.2 ng/ml (n=6) (P<0.23), respectively. The severity of diabetes mellitus judged from the fasting plasma glucose level had no influence on the plasma leptin levels during OGTT, but the leptin levels decreased significantly during a tolerance test (P<0.001), and similar results were also seen during a breakfast test. The fasting plasma leptin in the male with FBS less than 140 mg/dl had a significant correlation with the fasting plasma IRI level, but this correlation disappeared after taking obesity into consideration. Thus the plasma leptin was chiefly dependent on the body weight and gender and had no special relation to diabetic severity.
 ...
PMID:Human plasma leptin in obese subjects and diabetics. 946 22

Plasma leptin shows a nocturnal rise and a pulsatile pattern. This work was undertaken to determine the effects of gender and obesity on this pattern. Twenty-four-hour leptin profiles were evaluated in 31 subjects [17 male, 14 female; age: 36 +/- 2 yr (mean +/- SEM); body mass index: 27.5 +/- 1.0 kg/m2]. Plasma leptin profiles were higher in obese (body mass index > 27 kg/m2) than in lean subjects and higher in women than in men, regardless of fat mass. Leptin showed diurnal rhythmicity with peaks between 2200-0300 (median: 0120) and nadirs between 0800 and 1740 (median: 1033). Spectral analysis revealed 2 components (periodicities: 24 and 12 h) with higher relative amplitudes in lean than in obese subjects. The relative diurnal amplitude also was higher in men than in women, controlling for adiposity. Insulinemia, female sex, and age were negative determinants of diurnal rhythm relative amplitude. Pulse analysis revealed 3.6 +/- 0.3 pulses/24 h, occurring mostly 2-3 h after meals. Pulse frequency correlated negatively with fat mass and insulinemia (Spearman's r = -0.54 and -0.37, respectively; P < 0.05 for each). Thus, obesity is associated not only with higher leptin levels but also with blunted diurnal excursions and dampened pulsatility. This abnormal rhythmicity may contribute to leptin resistance in obesity. The significance of the sexual dimorphism in the diurnal amplitude is unclear, but it may be related to leptin's putative role as a metabolic signal to the reproductive axis.
 ...
PMID:Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. 946 57

Leptin affects body weight and reproduction mainly via receptors in the central nervous system. Different isoforms of the leptin receptor (leptin-R) exist, including a long isoform (leptin-RL) with signalling capacity and short isoforms (leptin-RS) with unknown function. The aim of this study was to examine leptin-R gene expression in different regions of the brain under conditions with altered body weight, in the female rat, including ovariectomy (OVX), oestradiol (E2) treatment, fasting and a genetic model of obesity (Zucker fa/fa). Leptin-R gene expression was analysed by in situ hybridization using probes recognizing all receptor isoforms (leptin-R) or specifically leptin-RL. Transcripts recognized by the leptin-R probe were abundant in the choroid plexus (CP), arcuate nucleus (ARC), ventromedial nucleus (VMN), thalamus (TH) and piriform cortex (PC). Leptin-RL transcripts were detected in the ARC, VMN, TH and PC but not in the CP. Although no sex difference was observed, leptin-R gene expression was reduced by E2 administration and increased by OVX. Administration of E2 reduced leptin-RL gene expression in the ARC and VMN but did not alter the expression in the TH or PC. OVX had no effect on the expression of leptin-RL mRNA. Fasting also caused a differential regulation of leptin-R mRNAs, with an increase in abundance of leptin-RL transcripts in the TH despite a decrease in leptin-R in this area. Obese Zucker rats had a similar pattern of expression with an increased expression of leptin-RL transcripts in all brain areas analysed and a decrease in leptin-R gene expression. These results demonstrate a differential regulation of leptin-RL and leptin-RS which could provide a mechanism for regulating access to, and sensitivity of, discrete regions of the brain for circulating leptin. We suggest that fasting and E2 alter the balance between leptin-RL and leptin-RS and that this could increase tissue sensitivity to leptin.
 ...
PMID:Differential expression and regulation of leptin receptor isoforms in the rat brain: effects of fasting and oestrogen. 948 66

Leptin is secreted from adipose tissue, and is thought to act as a 'lipostat', signalling the body fat levels to the hypothalamus resulting in adjustments to food intake and energy expenditure to maintain body weight homeostasis. In addition, plasma leptin concentrations have been shown to be related to insulin sensitivity independent of body fat content, suggesting that the hyperleptinemia found in obesity could contribute to the insulin resistance. We investigated the effects of leptin on insulin binding by isolated adipocytes. Adipocytes isolated from Sprague-Dawley rats exhibited a dose-dependent reduction in the uptake of 125I-labelled insulin when incubated with various concentrations of exogenous leptin. For example, addition of 50 nM leptin reduced total insulin binding in isolated adipocytes by 19% (P < 0.05). Analysis of displacement curve binding data suggested that leptin reduced maximal insulin binding in a dose-dependent manner, but had no significant effect on the affinity of insulin for its binding site. We conclude that leptin directly inhibited insulin binding by adipocytes, and the role of leptin in the development of insulin resistance in obese individuals requires further investigation.
 ...
PMID:Leptin inhibits insulin binding in isolated rat adipocytes. 948 6

The role of leptin in humans remains controversial. Leptin concentrations are highly correlated with body fat stores. We tested whether or not this relation was consistent across the range of body composition encompassing the lean as well as the obese. Individuals participating in community-based comparative research in Nigeria (n = 363), Jamaica (n = 372), and the United States (Maywood, IL; n = 699) had their plasma leptin concentrations and body compositions (with bioelectrical impedance analysis) measured. All participants identified themselves as being black. Body mass index (in kg/m2) ranged from 14 to 62. Large differences in mean plasma leptin were noted across populations for both men and women in Nigeria, Jamaica, and the United States, respectively (men: 2.8, 3.9, and 6.8 microg/L; women: 10.3, 18.6, and 27.7 microg/L). An exponential function fit the relation between percentage body fat or total fat mass and leptin for men and women at each site. For women and men the exponential function with either percentage body fat or total fat mass was of the same shape, but increased by a constant in women, yielding higher leptin concentrations than in men at every level of body fat. On the basis of this broad distribution of body composition, the data suggest an exponential response of leptin to increases in body fat stores, consistent with the development of leptin resistance in individuals developing obesity. These findings likewise confirm that men and women exhibit different set points in terms of leptin production.
 ...
PMID:Leptin and body composition of Nigerians, Jamaicans, and US blacks. 949 75

Leptin (from the Greek leptos=thin) was identified only 3 years ago. It has attracted huge attention both scientifically, with more than 600 publications, and in the media, where this protein has been portrayed as the way to a cure for obesity. Indeed, leptin was first described as an adipocyte-derived signalling factor, which, after interaction with its receptors, induced a complex response including control of bodyweight and energy expenditure. Leptin seems in addition to its role in metabolic control to have important roles in reproduction and neuroendocrine signalling. Human obesity is a complex disorder, with many factors playing a part; the pathophysiology of leptin is not as simple as it seems to be in rodent models of obesity.
 ...
PMID:Leptin. 950 34

Leptin is a 16-kD protein encoded by the ob/ob (obesity) gene. In rodents it plays a role in obesity, diabetes, fertility, and neuroendocrine function. In humans serum concentrations of leptin correlate with total body fat in both adults and children. We measured cord blood leptin in 186 neonates that included 82 appropriate for gestational age (AGA), 47 large for gestational age (LGA), 20 infants of diabetic mothers, 52 preterm infants, and 15 intrauterine growth-retarded (IUGR) infants. There were 16 pairs of twins. The mothers of 17 preterm infants were treated with steroids before delivery. Leptin (mean +/- SD) concentration in term, AGA infants (39.4 +/- 1.1 wk) with birth weight (BW) of 3.2 +/- 0.3 kg, body mass index (BMI) of 12.6 +/- 1.1 was 4.01 +/- 3.5 ng/mL. BW correlated with cord leptin (p = 0.002) in a multivariate analysis controlling for potential confounders. Both LGA infants and infants of diabetic mothers had higher cord leptin concentration 7.3 +/- 3.8 and 6.1 +/- 4.8 ng/mL, respectively, compared with AGA infants (p < 0.05). Preterm infants had a mean leptin level of 1.8 +/- 0.97 ng/mL and a 3-fold elevation was seen if mothers received steroids antenatally (p = 0.006). IUGR infants had increased leptin (6.5 +/- 3.9 ng/mL, p = 0.03). Concerning the twin pairs, the smaller had a higher leptin level compared with larger twin (4.1 +/- 9.51 versus 2.8 +/- 5.14, p = NS). Neonatal cord leptin concentrations correlate well with BW and BMI. No gender differences were found in cord blood leptin. Maternal obesity had no effect on cord leptin, whereas exogenous maternal steroids increased neonatal leptin concentrations.
 ...
PMID:Neonatal cord blood leptin: its relationship to birth weight, body mass index, maternal diabetes, and steroids. 950 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>