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)

A brief review of the studies on the obese (ob) gene is given. The ob gene is a mouse gene, the mutations of which are associated with altered metabolism and increased lipid deposits in adipose tissue. Recessive ob gene mutations in homozygous mice result in obesity and diabetes mellitus. Both mouse and human ob cDNAs were cloned and sequenced using positional cloning, exon trapping, and PCR. Of ten tested tissues, the ob gene was expressed only in white adipose tissue. The ob gene cDNA has a region of the nucleotide sequence with an opening reading frame and encodes the ob protein consisting of 167 amino acid residues. Mouse and human ob proteins showed a 85% homology. The 145-amino acid peptide termed as leptin and derived from ob protein after cleavage of signal peptide is secreted in the blood and stimulates fat consumption in energy metabolism. The biologically active ob peptide has been obtained by gene engineering methods. Administration of the ob protein to ob/ob mice reduced body weight and abolished symptoms of diabetes. The ob protein lowered body weight also in healthy animals. It was biologically effective both upon parenteral and intravenous administration and also when injected into lateral ventricle of the brain. With a polyclonal antiserum against the peptide the ob protein was shown to be present in human and mouse plasma and mouse adipose tissue. Based on the data obtained, it is postulated that the ob gene protein product leptin, is a hormone, which is secreted by adipocytes in the blood in varying amounts and regulates the mass of adipose tissue by stimulating lipid metabolism. Similarly to adipocytes, many other organs and tissues are presumably endocrine and may secrete peptide hormones in the blood. This considerably extends the scope of endocrinology and makes it necessary to review the existing concepts and views.
 ...
PMID:[ob protein--product of expressing an obesity gene and some aspects of modern-day endocrinology]. 901 Dec 50

Obesity--an important problem in modern societies--is caused by energy balance dysregulation and produces numerous adverse effects on health. Recently a particular attention has been paid to molecular and physiological mechanisms in the development of obesity and to the signalling role of adipose tissue in energy stores maintenance on the hypothalamic level. Leptin, the obese gene product discovered in 1995, may play a key role in the feedback system between adipose tissue and the ventromedial nucleus of the hypothalamus (satiety centre). The level of ob gene expression in adipose tissue and plasma leptin concentrations in humans are highly correlated with BMI. So far no mutations in the ob gene in obese subjects have been reported therefore leptin molecule could be active. Despite markedly increased leptin levels found in obesity its central action decreasing food intake and increasing energy expenditure is hindered. Defective ob protein signalling to the brain may be due to receptor and post-receptor defects. Neuropeptide Y, the hypothalamic neurotransmitter involved in the maintaining of energy homeostasis, is a likely candidate for mediating leptin afferent signals. In adipose tissue, the level of ob mRNA is regulated by insulin and glucocorticoids--hormones responsible for glucose homeostasis as well as for the central regulation of feeding behaviour. Until now the character of interactions between leptin and other hormones that regulate energy balance is not known, neither is the exact nature of leptin hypothalamic receptor defect. Defining of the role of leptin in the regulation of satiety and energy expenditure will undoubtedly contribute to a better understanding of the pathogenesis of obesity and its related metabolic complications and may lead to a new treatment approach to human obesity based on leptin or its analogues. At present research work focuses on leptin receptor studies and on ob gene polymorphism and its expression in feeding disorders including obesity and anorexia nervosa. The ob gene is one of a few genes involved in energy balance, however, very promising one.
 ...
PMID:[The ob gene product (leptin)--a new hormone of adipose tissue]. 938 Aug 11

Obesity produces a variety of alterations in the reproductive system and, similarly, manipulations of the hypothalamic-pituitary-gonadal axis produce changes in food intake, body weight and fat distribution. In men, the primary effects of obesity are a weight related reduction in testosterone and, with massive overweight, a reduction in free testosterone. In females, the weight-related development of menarche leads to earlier menarche in obese girls than in normal weight girls. One explanation for the relationship of fatness to menarche may be the ob protein (leptin) which is defective in the obese (ob/ob) mouse. Leptin is secreted by adipose tissue in proportion to the quantity of fat and may serve as a signal to the hypothalamus that fat stores are adequate to nourish a conceptus to term. In women, parity affects obesity and obesity in turn affects the regularity of the menstrual cycle. In many experimental animals with obesity, particularly the genetic forms of obesity, there is complete infertility in the females and marked impairment of reproductive function in the males. In animals with hypothalamic lesions, there is a gender effect on the magnitude of weight gain associated with the sexually dimorphic regions in the medial preoptic area. Castration with removal of oestrogen is followed by obesity in female animals and this can be prevented, as can most forms of obesity, by adrenalectomy. The inhibitory effects of oestrogen on food intake may result from suppression of neuropeptide-Y or galanin peptidergic systems in the arcuate nucleus or medial preoptic area.
 ...
PMID:Obesity and reproduction. 940 19

Leptin is a secretory product of adipocytes. It has been suggested that leptin acts as an afferent satiety signal to the brain modulating the expression of the orexigenic hypothalamic peptide, neuropeptide Y (NPY). Therefore leptin can be regarded as a marker of the nutritional status of the body. It was proposed that human obesity may result from a central resistance to leptin due to different pathophysiological mechanisms: saturation of the leptin transport into the cerebrospinal fluid of the obese subjects, abnormalities in the hypothalamic receptor for leptin, or post-receptor transduction mechanisms. It was shown that circulating leptin levels in humans significantly correlate with the body mass index (BMI). Although most studies point to white adipose tissue as a primary source of leptin there is still some uncertainty towards the relative expression of leptin between various body fat compartments. LEPTIN AND ONSET OF PUBERTY: Studies on animal models recognized various metabolic candidates for modulation of GnRH neuronal activity. It was supposed that mild changes in the body's metabolic status can serve to regulate the central drive to the reproductive axis. It is likely that leptin can serve as a "metabolic cue" that transmits signals of those mild metabolic changes towards activation of the GnRH neuronal system at the end of the prepubertal period. On the other side there is a possibility of altered leptin pulsatility during prepubertal period that can consequently influence hypothalamus and GnRH neuronal system. LEPTIN AND SEXUAL DIMORPHISM: Leptin levels in humans are similar in both sexes during the prepubertal period. During puberty leptin has a tendency to decline in boys and to remain constant in girls. Puberty is also characterized with a similar circadian rhythm pattern between sexes whil girls express different pulse characteristics. It seems that sexual dimorphism is established in early phases of human development. There is a possibility of sex steroid influence on such sexual dimorphism. LEPTIN AND REPRODUCTIVE FUNCTION: It was shown that administration of recombinant leptin to ob ob mice could restore fertility in these infertile animals. There is certain difference in leptin levels according to the phase of the menstrual cycle. It was shown that leptin peak is in the luteal phase of the cycle and that correlates to the maximal progesterone level. It is possible that leptin could directly influence ovary and that disruption of such an effect could play a role in menstrual irregularities in both obese and mal nourished women. This could even become a pathophysiological mechanism in women with polycystic ovary syndrome (PCOS). It was supposed that leptin resistance could be involved in infertility impairment of the obese women with PCOS. Leptin increases during pregnancy. Appearance of placenta as a new, nonadipose source of leptin production, increases a possibility of different leptin mRNA expression through gestation.
 ...
PMID:[Leptin and human reproduction]. 986 30

From February to June in 1996, there were 47,800 students for health examination in Taichung City, Taiwan. The population consisted of the first and fourth graders of primary schools and the first grader of junior high schools. We selected 3,452 healthy students for further study by two stage sampling. In this report, 52.5% of the students were boys, and 47.5% of the students were girls. The mean age of students was 9.9 +/- 2.4 years. Girls at age 7 and age 10 had higher activity of alkaline phosphatase than boys at the same age. The peak of alkaline phosphatase activity in girls occurred at age 10. Alkaline phosphatase activity was significantly related to weight-length index by multiple regression analysis (p < 0.05). Although clinical application as an obesity factor still needs further investigation, in the future it may be well to routinely check this enzyme when assessing childhood obesity.
 ...
PMID:Plasma alkaline phosphatase activity in children and adolescents. 992 12

In order to study the relationship between obese protein and obesity. A radioimmunoassay for human plasma obese protein (OP) was established using human OP (57-92) and its specific antiserum. We observed the distribution and the characteristics. Of OP in normal human and mouse tissue and changes of plasma OP in obese patients. We also observed the tissue distribution after intravenous injection of 125I-labeled OP fragments (116-167) and (93-105) in rats. The results were as follows. The contents of OP were much higher in brain tissue than those in abdominal adipose tissue; levels of OP in liver and in skeletal muscle tissue were zero; the contents of abdominal adipose tissue were higher in female mice than those in male mice; the contents of plasma OP in normal human beings were 194.3 +/- 17.7 ng/L, while those in mice were 2257.8 +/- 171.9 ng/L. It was also found that the administered OP fragments were widely distributed in various tissue and organs including the brain. Kidney was the richest in the OP fragments; liver and lung ranked second. The half time of the OP fragments in plasma clearance was about 4.5 min. The contents of OP in obese adults and in obese children were much lower than those in normal control group. There was significant negative correlation between OP levels and body mass index, serum concentration of glucose, cholesterol and triglycerides. So the present study indicates the important relationship between the changes of OP contents and the pathogenesis of obesity.
 ...
PMID:[Relationship between obese gene expressive product and obesity]. 1037 12

Hyperphagia (overeating) is often associated with energy over-storage and obesity, which may lead to a myriad of serious health problems, including heart disease, hypertension, and type 2 diabetes. Thus, understanding the complex pathological mechanisms underlying hyperphagia and obesity has an important clinical significance. Leptin, or ob protein, is a key element in the long-term regulation of food intake and body weight homeostasis. It circulates in the blood at levels correlated with body fat mass. Leptin binds to specific receptors in the hypothalamus to mediate events that regulate feeding behavior. In light of new evidence, the initial view that leptin is an adipocyte-derived signal, which acts centrally to decrease body weight, has been modified. It has been shown that leptin may also have specific functions in the gastrointestinal tract, suggesting that feeding and energy homeostasis is regulated by both central and peripheral signals. Evidence supports the view that leptin integrates short-term, meal-related signals from the gut into long-term regulation of energy balance. In addition, the gastric leptin level is altered by the nutritional state and the administration of cholecystokinin. This commentary aims to review the evidence of the role of leptin as a peripherally acting signal in the gut in the regulation of nutrient intake, adiposity, and body weight. Based on currently available data, some potential future studies are suggested.
 ...
PMID:Leptin, gut, and food intake. 1200 60

Obese individuals with glucose intolerance present with high serum levels of glucose, insulin, and leptin. These substances are potent inhibitors of feeding in the brain. Obese subjects still present with over-feeding despite elevation of the above factors. To elucidate the mechanism of this paradox, the effects of insulin and glucose on the anorectic action of leptin in the hypothalamus were examined. Adult male Sprague-Dawley rats (weighing 285-320 g) were pretreated with intracerebroventricular injection of insulin, glucose, or saline, followed by leptin (7.5 microg) or phosphate-buffered saline (PBS) injection into the third cerebral ventricle (icv). The cumulative food intakes were measured 24 hr after leptin icv. The tyrosine phosphorylation of signal transducer and activator transcription factor 3 (STAT3) in the hypothalamus was determined by Western blotting. In rats pretreated with saline and stimulated with leptin (saline/LEPTIN group), food intake diminished to about 50% of that of the saline/PBS group (P < 0.005). Food intake in the insulin/LEPTIN group was significantly higher compared with the saline/LEPTIN group (P < 0.005) and reached the level seen in the saline/PBS group. Similar data were obtained in glucose pretreatment experiments. Insulin and glucose icv resulted in reduction of leptin-induced STAT3 tyrosine phosphorylation compared with saline. Infusion of insulin and glucose icv did not alter peripheral blood glucose levels in all groups. High insulin or glucose levels in the brain could result in leptin resistance as manifested by food intake, which is probably due to the attenuation of STAT3 phosphorylation downstream the leptin receptor.
 ...
PMID:Intracerebroventricular administration of insulin and glucose inhibits the anorectic action of leptin in rats. 1461 Feb 54

Leptin is a hormone involved with satiety and energy balance and proposed to be an anti-obesity factor. Much effort has been dedicated to the relationship between leptin and bone. This interest stems from the knowledge that body weight is a major determinant of bone density. It is known that obese persons have stronger bones and lose bone tissue at a slower pace. Therefore, attention has been given to leptin as a mediator of increased osteogenesis. Leptin has been shown to play a role on bone both in vitro and in vivo. The administration of leptin in vitro induced the expression of leptin receptors on stromal cells, the differentiation to osteoblasts and inhibition of differentiation into the adipocyte phenotype. In addition, leptin was able to inhibit osteoclastogenesis of peripheral blood mononuclear cells. Therefore, there is in vitro and experimental evidence that leptin is able both to stimulate osteoblasts and inhibit osteoclast differentiation. This would be in line with the hypothesis that the correlation between obesity and increased BMD is linked to leptin activity. However, experimental results are indicative of a role of CNS in mediating the effect of leptin on bone metabolism. These effects are opposite to the direct effects on bone cells and lead to bone loss. To solve the problem, it has been suggested that obese individuals have a resistance of nervous structures to leptin. In chronic renal failure serum leptin levels are markedly increased. An inverse correlation between histomorphometric parameters of bone turnover and serum leptin levels and between leptin and PTH have been reported. Therefore, the hypothesis has been raised that leptin lowers bone turnover in chronic renal failure. Since leptin has a direct stimulatory effect on bone and an indirect opposite effect via the CNS, it has been suggested that in CRF a resistance of nervous structures to leptin, like in obesity, may be present. By now, coherent findings suggest that the prevailing effect of leptin on bone in ESRD is that of reducing bone turnover.
 ...
PMID:Leptin and bone metabolism. 1529 17

Synthesized and released by the adipose tissue, leptin is the widely studied 167-amino acid hormonal protein product of the obesity gene. Originally leptin was defined in association with satiety and energy balance and claimed to be an anti-obesity factor that functioned via a feedback effect from adipocytes to hypothalamus. There is a growing body of evidence that emphasizes the importance of leptin in the regulation of food intake and body weight in animals and humans, alike. Other research findings point out that it plays a role in the regulation of the metabolism, sexual development, reproduction, hematopoiesis, immunity, gastrointestinal functions, sympathetic activation, and angiogenesis. The aim of this review is to evaluate the relation between leptin and the central nervous system (CNS).
 ...
PMID:Leptin transport in the central nervous system. 1920 4


<< Previous 1 2 3 Next >>