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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently demonstrated the nocturnal increase in leptin secretion in humans. In the present study we have examined the pulsatile pattern of leptin secretion using two different experimental protocols. The first protocol utilized blood samples withdrawn at 30 minute intervals immediately after meals, at 1 hour intervals between meals, and at 2 hour intervals during the night from 4 lean, 11 obese, and 5 obese NIDDM subjects. Analysis of circulating leptin levels by ULTRA algorithmic program and using matched intra-assay coefficient of variations demonstrated 1 to 7 ultradian oscillations with a mean of 3.25 +/- 0.36 (SEM) pulses per 24 hour period (period: 10.0 +/- 1.5 hours; mean relative amplitude: 0.52 +/- 0.06, n = 20). Significant positive correlations were observed for changes in absolute amplitude with body mass index (p < 0.025) and fasting leptin levels (< 0.0001). In the second series of experiments utilizing 15 minute blood sampling from 10 overnight fasted obese subjects (BMI 35.9 +/- 2.0 kg/m2), ultradian oscillations for leptin were more frequent, i.e., 2 to 7 oscillations (4.20 +/- 0.59), over a 12 hour duration (period: 3.44 +/- 0.49; mean relative amplitude: 0.28 +/- 0.03). The number of oscillations over a 12 hour period correlated significantly with BMI (p < 0.001), fasting leptin levels (p < 0.01), and absolute amplitude (p < 0.005) in a 15 minute sampling protocol. In summary, similar to other hormones, ultradian oscillations of leptin are observed in humans, although the physiological significance in relation to obesity or feeding behavior is not yet understood.
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PMID:Ultradian oscillations of leptin secretion in humans. 894 46

Obesity is common and its prevalence is rising. In Singapore, a national health survey in 1992 showed that 5% of the adult population were obese and 21% were overweight. Obesity causes much morbidity and mortality and treatment is desirable. The majority of obese patients have no known cause but it is essential to exclude any underlying cause before treatment. Antiobesity drugs should be used as an adjunct to an adequate programme of dietary restriction, exercise and behavior modification. Serotonergic drugs and adrenergic agents are available in the treatment of obesity. The short-term efficacy and safety of antiobesity drugs such as fenfluramine and d-fenfluramine are proven. The long-term use of antiobesity drugs used singly or in combination remains to be established. Many peptides (cholecystokinin, glucagon, bombesin, neurotensin, etc) with weight reduction properties are undergoing extensive studies: their clinical applications are experimental. The treatment of obesity is difficult and frustrating and antiobesity drugs have an established short-term role. In morbid obesity where the life of the patient is in danger, surgery such as gastric plication may be life-saving. The recent discovery of leptin (1994) and neuropeptide Y (1995) are important breakthrough in obesity research; hopefully further research may produce more effective treatment of obesity in man.
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PMID:Current management of obesity. 894 35

Many cytokines exert their biological effect through members of the hemopoietin receptor family. Using degenerate oligonucleotides to the common WSXWS motif, we have cloned from human hemopoietic cell cDNA libraries various forms of the receptor that was recently shown to bind the obesity hormone, leptin. mRNAs encoding long and short forms of the human leptin receptor were found to be coexpressed in a range of human and murine hemopoietic organs, and a subset of cells from these tissues bound leptin at the cell surface. Ectopic expression in murine Ba/F3 and M1 cell lines revealed that the long, but not the short, form of the leptin receptor can signal proliferation and differentiation, respectively. In cultures of murine or human marrow cells, human leptin exhibited no capacity to stimulate cell survival or proliferation, but it enhanced cytokine production and phagocytosis of Leishmania parasites by murine peritoneal macrophages. Our data provide evidence that, in addition to its role in fat regulation, leptin may also be able to regulate aspects of hemopoiesis and macrophage function.
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PMID:Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. 896 92

Identification of the OB (leptin) receptor (OBR) as the gene that is defective in diabetes (Leprdb) mice and fatty (Leprfa) rats provides an important candidate gene for the study of the genetics of human obesity. We defined the boundaries of the 18 coding exons for the long form of OBR, and sequenced the immediately adjacent intronic regions. These sequences can be used to generate reagents for genetic analysis (e.g., direct sequencing, single-stranded conformational polymorphism analysis, etc.) of the possible role of OBR in the regulation of adiposity in humans. In addition, we have identified two highly polymorphic intronic microsatellites that can be scored with the polymerase chain reaction.
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PMID:Genomic structure of the human OB receptor and identification of two novel intronic microsatellites. 897 14

Numerous endocrine alterations are associated with obesity (Table 1). The majority of the alterations are secondary to obesity and must be considered simply associated and potentially in the pathogenesis of the complications of obesity. The discovery of new endocrine peptides such as leptin that signal body fat content will increase our understanding of the regulation of body fat content. As a result, therapies will most certainly be developed that are directly targeted at the alterations in endocrine function.
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PMID:The endocrinology of obesity. 897 53

Obesity is a complex disease which results from the interaction of multiple genes and the environment. The recently discovered genes for leptin (ob gene) and the leptin receptor appear to play a major regulatory role in body energy balance and adipose tissue deposition. Furthermore, defects in the ob gene and leptin receptor gene have been demonstrated to be the cause of obesity in several rodent models. These observations raise the possibility that human obesity may also be due to defects in the leptin signal system. This review will summarize the current findings on the ob gene, leptin and the leptin receptor in both animals and humans. These observations will be discussed in the context of potential defects in the system and the possibility that these defects result in obesity in humans.
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PMID:Leptin: genes, concepts and clinical perspective. 898 34

Leptin may play an important role in the regulation of body weight by influencing energy intake and expenditure. Differences in body composition, resting energy expenditure (REE), and physical activity between African-American and Caucasian women could be reflective of racial differences in plasma leptin concentrations. Thus, we examined racial differences in leptin levels and the relationships of leptin to body composition and resting metabolism in obese postmenopausal African-American (n = 28) and Caucasian (n = 29) women matched for level of body fat. African-American and Caucasian women were similar in age (64.1 +/- 1.3 vs. 63.2 +/- 1.0 yr), body weight (84.7 +/- 3.3 vs. 80.4 +/- 1.3 kg), adipose tissue mass (39.7 +/- 2.8 vs. 38.0 +/- 1.0 kg), waist to hip ratio (0.81 +/- 0.02 vs. 0.81 +/- 0.01), and maximal aerobic capacity (1.5 +/- 0.05 vs. 1.6 +/- 0.05 L/min). African-American women had greater lean tissue mass than Caucasian women (41.8 +/- 1.1 vs. 39.3 +/- 0.6 kg; P = 0.05). The leptin concentration was 20% lower in African-American than Caucasian women (36.0 +/- 4.8 vs. 45.8 +/- 3.5; P < 0.05), whereas REE values were similar. Leptin correlated strongly with percent body fat in African-American (r = 0.71; P < 0.0001) and Caucasian women (r = 0.61; P < 0.001) and with REE in African-American (r = 0.58; P < 0.001), but not Caucasian, women (r = 0.08). These findings suggest racial differences in plasma leptin levels and in leptin's role in the regulation of REE, which may play a role in the greater incidence of obesity in the African-American compared to the Caucasian population.
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PMID:Racial differences in plasma leptin concentrations in obese postmenopausal women. 898 80

A growing body of evidence suggests that energy balance (the difference between energy intake and expenditure) and body fuel stores in the form of adipose tissue are maintained by the body within a narrow range. This regulation of adiposity is mediated by the secretion of hormonal signals into the circulation in proportion to body adipose stores and their subsequent actions on brain systems that control caloric intake and energy expenditure. As a result, changes in energy balance sufficient to alter fuel stores elicit compensatory changes in energy intake and expenditure that return fat stores to their regulated level. Recent scientific break-through have identified the key components of this physiologic system. These include the circulating signals, leptin (the hormone encoded by the ob gene that is secreted by fat cells) and the pancreatic hormone insulin; and brain peptides such as neuropeptide Y, which is released from nerve terminals in the hypothalamus to elicit changes in feeding behavior and energy expenditure that mediate adaptive changes in energy balance. This article reviews the discovery of leptin and its receptor and discusses the interaction of leptin and insulin with the hypothalamic neuropeptide Y system. These observations provide a basis for understanding how weight lost during a period of negative energy balance (because of the inability to consume and/or store sufficient energy to meet ongoing energy demands) is eventually recovered. As our understanding of this weight-regulatory system increases, new insights into the causes of human obesity are likely to follow. Such insights may yield improvements in the medical and nutrition management of obese patients.
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PMID:The new biology of body weight regulation. 899 Apr 18

A highly conserved protein called 'leptin' was recently discovered to play a role in regulation of the energy balance in humans and rodents. This 167-amino-acid-containing protein is only produced and secreted by mature adipocytes. Absence of the protein in mutant ob/ob mice and resistance to its effects in db/db mice lead to extreme obesity and type II diabetes mellitus. No mutation of the ob-gene encoding for leptin has been found in obese humans so far. ob mRNA in adipocytes and serum leptin levels are positively related to adipose tissue mass. Receptors for leptin have been found in the choroid plexus and hypothalamus. A feedback inhibition of leptin on hypothalamic neuropeptide Y (NY) production is postulated, as hypothalamic NY concentrations are increased in ob/ob mice and NY induces food intake, insulin secretion and autonomic nervous system activity. Insulin increases triglyceride stores in fat cells and could thereby stimulate leptin secretion. The ultimate intracellular pathway within the adipocyte that stimulates or shuts off ob mRNA expression and consequent leptin production and secretion remains to be elucidated. Whether leptin will ever come to play a role in the treatment of human obesity remains an unanswered question at the present time.
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PMID:Leptin. 899 Aug 65

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.
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PMID:[ob protein--product of expressing an obesity gene and some aspects of modern-day endocrinology]. 901 Dec 50


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