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)

It is concluded that besides NA, some other hormones (adrenaline, glucagon, growth hormone, ACTH, insulin and adrenal steroids) are also thermogenic. While brown adipose tissue is the most important site of heat during NA thermogenesis, some other organs, namely muscles, also contribute to thermogenesis due to various hormones. Hormones seem to potentiate heat production due to their action in target organs. Humoral thermogenesis not only can compensate the heat loss from the body of cold exposed individuals, but it can also prevent obesity under conditions of an high caloric intake. Some substance, on the other hand, induce a hypometabolic effect (rT3, hibernation trigger, antabolone, bombesin). Additionally, absence of gonadal steroids induce hibernation. Thus, humoral substances contribute both to the control of hyper- and hypometabolic states.
 ...
PMID:Humoral control of hyper- and hypometabolic states. 631 84

The concentration of cholecystokinin (the octapeptide, CCK-8), bombesin, and neurotensin was measured by radioimmunoassay in the cortex, hypothalamus and diencephalon of brains from lean, genetically obese and hypothalamic (VMH) obese rodents. Highest concentration of CCK-8 was found in the cortex whereas highest concentrations of bombesin and neurotensin were in the hypothalamus. When food was provided ad libitum, there was no difference in concentration of any of these peptides between lean and the respective genetically obese mice (ob/ob) and fatty (fa/fa) rats, or between lean and hypothalamic (VMH lesioned) obese rats. Adrenalectomy, which arrested the progression of obesity in both ob/ob and fatty rats, did not result in significant change in concentration of any of the three peptides studied in comparison with the respective sham-operated animals. Though significant differences in cholecystokinin and bombesin concentrations were detectable in some instances between adrenalectomized lean and adrenalectomized obese rats, these differences did not appear to be related to fall in food intake or slowing of body weight gain. Thus a variety of manipulations which altered the nutritional plane of the experimental rodents was not accompanied by significant changes in brain concentrations of cholecystokinin, bombesin or neurotensin.
 ...
PMID:Cholecystokinin, bombesin and neurotensin in brain tissue from obese animals. 672 99

Disturbed satiety mechanisms may contribute to obesity. There has been speculation that cholecystokinin (CCK) and pancreatic polypeptide (PP) are involved in the regulation of satiety. We have therefore investigated whether there are differences between healthy lean and healthy non-diabetic obese volunteers in plasma CCK or PP release after a neuropeptidergic stimulation with bombesin and after infusion of a mixed meal. There were no differences in plasma CCK between groups either basally or in response to either form of stimulation. However, the plasma PP concentrations after the meal were significantly less in obese (2845 +/- 404 pM.min) than in lean subjects (5569 +/- 997 pM.min), whereas the plasma PP concentrations during bombesin were similar in both groups. We tested two other groups of nine obese and lean subjects to determine whether a disturbed vagal function could be the cause of the diminished plasma PP in obese persons, by studying the effect of modified sham feeding (MSF) on plasma PP. However, there were no significant differences in the plasma PP response to MSF between lean and obese subjects. We conclude that there are no differences between lean and obese persons in plasma CCK secretion in response to infusion of the neuropeptide bombesin or to ingestion of a mixed meal. However, the plasma PP after a mixed meal, is markedly diminished in obese subjects. This could not be attributed to a disturbed vagal cephalic stimulation.
 ...
PMID:Plasma cholecystokinin and pancreatic polypeptide secretion in response to bombesin, meal ingestion and modified sham feeding in lean and obese persons. 814 26

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.
 ...
PMID:Current management of obesity. 894 35

Obesity is a major risk factor for morbidity and mortality, and a series of pharmacologic approaches are available for helping to manage the problem. Obesity is caused by an imbalance between caloric intake and energy expenditure, which is influenced by both environmental and genetic factors. Pharmacologic treatments include anorexigenic agents, which fall into two broad categories: those that act via brain catecholamine pathways and those that act via serotonin pathways. The most recent oral agents approved are dexfenfluramine, which is currently being marketed, and sibutramine. Both agents inhibit the control reuptake of serotonin but in addition may have effects on thermogenesis. Under investigation are agents that increase energy expenditure: the beta 3-adrenergic receptor agonists and drugs that prevent the intestinal absorption of free fatty acids and cholesterol. In development are innovative approaches to influence leptin and its receptors, various obesity genes, and biologic substances thought to influence satiety (neuropeptide Y, enterostatin, cholecystokinin, bombesin, and amylin). Obesity has now become a major target for drug development not only for affecting obesity per se but also for managing and preventing comorbid conditions such as diabetes and cardiovascular disease.
 ...
PMID:The pharmacologic approach to the treatment of obesity. 920 52

Mammalian bombesin-like peptides are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism and behaviour. They bind to G-protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors cloned so far include, gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). However, despite the molecular characterization of BRS-3, determination of its function has been difficult as a result of its low affinity for bombesin and its lack of an identified natural ligand. We have generated BRS-3-deficient mice in an attempt to determine the in vivo function of the receptor. Mice lacking functional BRS-3 developed a mild obesity, associated with hypertension and impairment of glucose metabolism. They also exhibited reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia. Our data suggest that BRS-3 is required for the regulation of endocrine processes and metabolism responsible for energy balance and adiposity. BRS-3-deficient mice provide a useful new model for the investigation of human obesity and associated diseases.
 ...
PMID:Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. 936 52

Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop obesity, hyperglycemia, and non-insulin-dependent diabetes mellitus and do not express cholecystokinin A (CCK-A) receptors, the receptor subtype mediating the satiety actions of CCK. In short-term feeding tests, male OLETF rats were completely resistant to exogenous CCK, and their response to bombesin was attenuated. Comparisons of liquid meal consumption in OLETF and control Long-Evans Tokushima (LETO) rats demonstrated that 1) OLETF rats had greater intakes during 30-min scheduled daytime meals and significantly larger and fewer spontaneous night-time meals and 2) although the initial rates of licking were the same, OLETF rats maintained the initial rate longer and the rate at which their licking declined was slower. In 24-h solid food access tests, OLETF rats consumed significantly more pellets than LETO controls, and this increase was attributable to significant increases in meal size. Together, these data are consistent with the interpretation that the lack of CCK-A receptors in OLETF rats results in a satiety deficit leading to increases in meal size, overall hyperphagia, and obesity.
 ...
PMID:Disordered food intake and obesity in rats lacking cholecystokinin A receptors. 953 Feb 26

Bombesin (Bn) receptor subtype 3 (BRS-3) is an orphan receptor that is a predicted member of the heptahelical G-protein receptor family and so named because it shares a 50% amino acid homology with receptors for the mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide. In a recent targeted disruption study, in which BRS-3-deficient mice were generated, the mice developed obesity, diabetes, and hypertension. To date, BRS-3's natural ligand remains unknown, its pharmacology unclear, and cellular basis of action undetermined. Furthermore, there are few tissues or cell lines found that express sufficient levels of BRS-3 protein for study. To define the intracellular signaling properties of BRS-3, we examined the ability of [D-Phe6,beta-Ala11,Phe13, Nle14]Bn-(6-14), a newly discovered peptide with high affinity for BRS-3, and various Bn receptor agonists and antagonists to alter cellular function in hBRS-3-transfected BALB 3T3 cells and hBRS-3-transfected NCI-H1299 non-small cell lung cancer cells, which natively express very low levels of hBRS-3. This ligand stimulated a 4-9-fold increase in [3H]inositol phosphate formation in both cell lines under conditions where it caused no stimulation in untransfected cells and also stimulated an increase in [3H]IP1, [3H]IP2, and 3H]IP3. The elevation of [3H]IP was concentration-dependent, with an EC50 of 20-35 nM in both cell lines. [D-Phe6,beta-Ala11,Phe13,Nle14]Bn-(6-14) stimulated a 2-3-fold increase in [Ca2+]i, a 3-fold increase in tyrosine phosphorylation of p125(FAK) with an EC50 of 0.2-0.7 nM, but failed to either stimulate increases in cyclic AMP or inhibit forskolin-stimulated increases. None of nine naturally occurring Bn peptides or three synthetic Bn analogues reported to activate hBRS-3 did so with high affinity. No high affinity Bn receptor antagonists had high affinity for the hBRS-3 receptor, although two low affinity antagonists for gastrin-releasing peptide and NMB receptors, [D-Arg1,D-Trp7,9, Leu11]substance P and [D-Pro4,D-Trp7,9,10]substance P-(4-11), inhibited hBRS-3 receptor activation. The NMB receptor-specific antagonist D-Nal,Cys,Tyr,D-Trp,Lys,Val, Cys,Nal-NH2 inhibited hBRS-3 receptor activation in a competitive fashion (Ki = 0.5 microM). Stimulation of p125(FAK) tyrosine phosphorylation by hBRS-3 activation was not inhibited by the protein kinase C inhibitor, GF109203X, or thapsigargin, alone or in combination. These results show that hBRS-3 receptor activation increases phospholipase C activity, which causes generation of inositol phosphates and changes in [Ca2+]i and is also coupled to tyrosine kinase activation, but is not coupled to adenylate cyclase activation or inhibition. hBRS-3 receptor activation results in tyrosine phosphorylation of p125(FAK), and it is not dependent on activation of either limb of the phospholipase C cascade. Although the natural ligand is not a known bombesin-related peptide, the availability of [D-Phe6,beta-Ala11, Phe13,Nle14]Bn-(6-14), which functions as a high affinity agonist in conjunction with hBRS-3-transfected cell lines and the recognition of three classes of receptor antagonists including one with affinity of 0.5 microM, should provide important tools to assist in the identification of its natural ligand, the development of more potent selective receptor antagonists and agonists, and further exploration of the signaling properties of the hBRS-3 receptor.
 ...
PMID:Ability of various bombesin receptor agonists and antagonists to alter intracellular signaling of the human orphan receptor BRS-3. 959 99

Rats maintained on high-fat diets often exhibit increased food intake and weight gain. We hypothesized that high-fat diets might result in reduced sensitivity to hormonal signals responsible for terminating food intake--satiety signals. The intestinal hormone cholecystokinin (CCK) and the gastrointestinal neuropeptide, bombesin (BBS) both have been proposed as satiety signals. To determine whether maintenance on high-fat diets alters sensitivity to satiating effects of CCK and bombesin (BBS), rats were maintained on a low fat diet (LF), a high-fat diet that was isocaloric with the low-fat diet (HF), or one of two hypercaloric high-fat diets (HF-1, HF-2) that differed from HF and LF in fat, fiber, and total caloric content. CCK and bombesin reduced food intake significantly less in rats maintained on high-fat diets, compared to those on the low fat diet. Neither high caloric intake, which was associated with increased body weight gain on the two hypercaloric diets, nor fiber content of the diet accounted for the reduced response of HF rats to CCK. Rather, reduced sensitivity to CCK was related only to the high proportion of calories taken as fat. We also determined whether reduced CCK sensitivity was due to the maintenance on a particular diet or to the diet eaten during a CCK test. After CCK, rats maintained on LF reduced food intake more (49%) than rats maintained on HF (22%), regardless of whether they ate HF or LF during the CCK test itself. These findings indicate that maintenance of rats on high-fat diets reduces sensitivity to some peptide satiety signals. Reduced sensitivity to satiety signals might contribute to overeating and obesity often observed when rats are maintained on high-fat diets.
 ...
PMID:Rats maintained on high-fat diets exhibit reduced satiety in response to CCK and bombesin. 980 56

This review is dealing with currently available medications used in the treatment of obesity. Unfortunately currently available drugs did not prove effective in the long term treatment of obese patients. Fenfluramin and D-Fenfluramin has been withdrawn from the market because of severe side effects as pulmonary hypertension and valvular heart disease. Sibutramin, a serotonin noradrenalin reuptake inhibitor, will be available this year. Orlistat, an inhibitor of pancreatic lipases, has proven effective for weight reduction in obese patients. New drugs as alpha 2-adrenergic antagonists, cholecystokinin, neuropeptide y, bombesin and leptin are in the pipeline.
 ...
PMID:[Drug therapy of obesity]. 987 89


<< Previous 1 2 3 4 5 Next >>