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)

Cholecystokinin (CCK) has been suggested as a putative satiety factor, whose site of action is in the hypothalamus. The genetically obese (fa/fa) Zucker rat has been proposed as a model of human obesity. Though hypothalamic tissue levels of CCK did not vary between the fa/fa rat and age-matched lean littermates (25.5 +/- 5.7 vs. 27.6 +/- 5.2 pmoles/g tissue) we sought to determine if the releasability of hypothalamic and cortical CCK was the same in lean and obese rats. The in vitro superfusion paradigm was used to study the release of CCK and substance P (sP) from hypothalamus, and CCK and vasoactive intestinal polypeptide (VIP) from frontal cortex. The potassium stimulated release of CCK from obese rat hypothalamic tissue was significantly higher than from lean rat hypothalamus (3.62 +/- 0.3 vs. 1.91 +/- 0.3 fmole equivalents CCK-8/mg tissue/10 min). Similarly, sP release was exaggerated in obese rats in a parallel fashion (5.56 +/- 0.44 vs. 2.761 +/- 0.46 fmoles/mg tissue/10 min). However, the potassium stimulated release of CCK and VIP from cortical tissue was the same in all three groups of rats. The obese Zucker rat thus, may have an anomalous release of CCK and sP from the hypothalamus, but not from the frontal cortex, an area not presumably associated with satiety.
 ...
PMID:In vitro, release of cholecystokinin from hypothalamus and frontal cortex of Sprague-Dawley, Zucker lean (Fa/-) and obese (fa/fa) rats. 620 Aug 66

Twenty-six patients who were more than 35 per cent above their ideal weight were examined before the introduction of a weight reduction programme. At the end of a three-month period, seven patients had lost more than 10 per cent of their body weight. These patients had significantly lower triglyceride levels, fasting gastric inhibitory polypeptide levels (GIP) and prolactin levels. Fasting vasoactive intestinal polypeptide levels (VIP) before commencing diet were raised in six of the 19 patients who subsequently did not lose weight whereas the seven patients who lost weight had normal VIP levels (X2 = 3.07, P less than 0.05). Patients with high VIP levels had higher triglyceride levels, higher mean C-terminal glucagon-like immunoreactivity (C-GLI) and higher post glucose infusion secretin levels. There was a significant correlation between triglycerides and VIP. The significance of abnormally high VIP levels in obesity and the inability of these patients to lose weight is discussed.
 ...
PMID:Vasoactive intestinal polypeptide in obesity. 634 22

The effect of insulin on polypeptide chain initiation and elongation has been studied in soleus muscles isolated from lean and goldthioglucose-obese mice. Insulin increased the amount of radioactivity present in nascent chains by approximately 30% in muscles from both lean and obese mice, indicating that it stimulates peptide chain initiation. In contrast, elongation rates, estimated by measurement of half transit time, were similar in basal conditions and insulin-treated muscles of lean and obese animals. Thus, insulin increased the initiation without modifying the elongation rates. Obesity did not affect either basal rates of initiation and elongation or the effect of insulin.
 ...
PMID:Insulin affects only initiation and not elongation in protein synthesis in soleus muscles of lean and obese mice. 675 57

Lean and genetically obese (ob/ob): mice were treated daily for 2 wk with thyroxine (T4), noradrenaline, or thyroxine plus noradrenaline. T4 treatment of obese mice increased the abnormally low binding of GDP to brown adipose tissue mitochondria and permitted a cold-induced increase to occur. It also brought about a return to a more normal ultrastructure of the mitochondria of the obese mice. T4 treatment did not alter the binding of GDP to brown adipose tissue mitochondria of lean mice. The binding of GDP to brown adipose tissue mitochondria is known to be to a 32,000-dalton polypeptide associated with the thermogenic proton conductance pathway. T4 treatment did not alter the proportion of this polypeptide in the mitochondrial membrane in either lean or obese mice. Treatment with noradrenaline did not alter the binding of GDP to brown adipose tissue mitochondria in either lean or obese mice. The effect of T4 is thought to be due to an improvement in the defective responsiveness of brown adipose tissue to endogenous noradrenaline in the obese mice, known to be related to their poor cold resistance and obesity. The improvement allows a more normal noradrenaline-induced unmasking of GDP binding sites, both in response to diet and in response to cold. Such treatment is known to improve cold resistance of the obese mice, and this appears to be correlated with an improvement in the functioning of their defective brown adipose tissue.
 ...
PMID:Abnormal brown adipose tissue in genetically obese mice (ob/ob): effect of thyroxine. 732 26

The possible involvement of nerves containing vasoactive intestinal polypeptide in Crohn's disease was investigated by immunocytochemistry and radioimmunoassay of specimens from 17 patients with well-defined clinical and histologic features of the disease. The characteristic pattern of slender fibers, evenly distributed across the gut wall, was seen in specimens taken from controls, which consisted of (a) specimens from uninvolved areas of gut from carcinoma resection (n = 17) and (b) jejunoileal specimens obtained during bypass operation for obesity (n = 8) as well as in four of the six specimens from patients with ulcerative colitis. In contrast, this characteristic pattern was lost in all 17 patients with Crohn's disease, the pattern being replaced by thickened and more intensely immunostained fibers. These changes were consistently found in the mucosa and submucosa, and in 13 of the Crohn's disease cases, the abnormal pattern was totally transmural, involving both the myenteric and submucous plexus as well as the muscle layers. There was a > 200% increase in VIP content, as determined by radioimmunoassay, in Crohn's disease (294 +/- 29 pmol/g wet wt, mean +/- SEM) in comparison with (a) ulcerative colitis (93 +/- 5 pmol/g [P < 0.001]), and (b) controls consisting of carcinoma resection (108 +/- 39) and bypassed gut from obese patients (86 +/- 27 [P < 0.001]). At least part of the previously documented autonomic nerve changes in Crohn's disease are, thus, due to an increase in vasoactive intestinal polypeptide innervation.
 ...
PMID:Abnormalities of vasoactive intestinal polypeptide-containing nerves in Crohn's disease. 741 8

Several dominant mutations at the agouti locus in the mouse cause a syndrome of marked obesity, hyperinsulinemia, and insulin resistance. Although it is known that the agouti gene is expressed in an ectopic manner in these mutants, the precise mechanism by which the agouti gene product mediates these effects is unclear. Since intracellular Ca2+ is believed to play a role in mediating insulin action and dysregulation of Ca2+ flux is observed in diabetic animals and humans, we examined the status of intracellular Ca2+ in mice carrying the dominant agouti allele, viable yellow (Avy). We show here that in mice carrying this mutation, the intracellular free calcium concentration ([Ca2+]i) is elevated in skeletal muscle, and the degree of elevation is closely correlated with the degree to which the mutant traits are expressed in individual animals. Moreover, we demonstrate that the agouti gene product is capable of inducing increased [Ca2+]i in cultured and freshly isolated skeletal muscle myocytes from wild-type mice. Based on these findings, we present a model in which we propose that the agouti polypeptide promotes insulin resistance in mutant animals through its ability to increase [Ca2+]i.
 ...
PMID:Agouti regulation of intracellular calcium: role in the insulin resistance of viable yellow mice. 776 89

The obese (ob) gene, the mutation of which results in severe hereditary obesity and diabetes in mice, has recently been isolated through positional cloning. In this study, we isolated a full-length human ob complementary DNA (cDNA) clone and examined the tissue distribution of ob gene expression in humans. The nucleotide sequences of the human ob cDNA coding region were 83% identical to those of the mouse and rat ob cDNA coding regions. Analysis of the deduced amino acid sequences revealed that the human ob protein is a 166-amino acid polypeptide with a putative signal sequence and is 84 and 83% homologous to the mouse and rat ob proteins, respectively. Northern blot analysis using the cloned human ob cDNA fragment as a probe identified a single messenger RNA (mRNA) species 4.5 kb in size found abundantly in the adipose tissues obtained from the subcutaneous, omental, retroperitoneal, perilymphatic, and mesenteric fat pads. However, no significant amount of ob mRNA was present in the brain, heart, lung, liver, stomach, pancreas, spleen, small intestine, kidney, prostate, testis, colon, or skeletal muscle. The ob mRNA level in the adipose tissue varied from region to region even in the same individual. Furthermore, in the human adipose tissue, ob gene expression occurred in mature adipocytes rather than in stromal-vascular cells. This study is the first report of the elucidation of ob gene expression in human tissues, thereby leading to better understanding of the physiological and clinical implications of the ob gene.
 ...
PMID:Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. 778 54

Amylin (islet-associated polypeptide) is a 37-amino acid peptide that is cosecreted with insulin from the pancreatic beta-cell. Accurate measurement of its plasma levels is important for delineating the physiological range over which amylin acts. We describe a reproducible, highly specific, and sensitive radioimmunoassay for direct measurement of plasma amylin-(1-37). We measured changes in portal and systemic plasma amylin and insulin in three groups of anesthetized rats: lean young adult and old adult Wistar rats with acquired obesity, and Wistar fatty [WDF/TaFa (fa/fa)] rats, a model of genetic obesity and insulin resistance derived from the Wistar strain. Changes in response to fasting, feeding, and intravenous stimulation with glucose plus arginine were assessed. We find that the amylin-to-insulin ratio is constant in fasted or fed young and old rats because of proportionate increases in both entities with aging. In genetically obese Wistar rats, amylin and insulin levels are three- to tenfold higher than in lean young or obese old normal controls. Islet stimulation by feeding or intravenous glucose plus arginine resulted in a decreased amylin-to-insulin molar ratio in all groups. When normalized for the degree of islet stimulation, amylin-to-insulin ratios were significantly elevated in genetically obese vs. normal rats, both in the portal and systemic circulation. These results demonstrate that aging-related weight gain in normal rats is associated with moderate and proportional increases in amylin and insulin, whereas genetic obesity is characterized by elevated amylin and an increased amylin-to-insulin ratio. Implications for the pathogenesis of insulin resistance and obesity are discussed.
 ...
PMID:Direct plasma radioimmunoassay for rat amylin-(1-37): concentrations with acquired and genetic obesity. 804 5

With the increase of obese children, harmfulness of obesity to their health was studied to lay a basis for formulating corresponding intervention measures. Blood sugar, intelligent quotient (IQ), thyroid function, cardiac and pulmonary function, and index of gonad development were determined in 150 obese children and 150 normal healthy children. Results showed baseline secretion of insulin and C-polypeptide in obese children were significantly higher than that in controls, and thyroid function, total IQ, speech IQ and operation IQ all were relatively lower, cardiac and pulmonary function was significantly lower, and gonad development and maturity took place earlier in the former than in those in the latter. It indicated that there were a lot of risk factors harmful to their health in obese children.
 ...
PMID:[Harmfulness of obesity in children to their health]. 875 52

The structure of the chemically synthesized C-terminal region of the human agouti related protein (AGRP) was determined by 2D 1H NMR. Referred to as minimized agouti related protein, MARP is a 46 residue polypeptide containing 10 Cys residues involved in five disulfide bonds that retains the biological activity of full length AGRP. AGRP is a mammalian signaling molecule, involved in weight homeostasis, that causes adult onset obesity when overexpressed in mice. AGRP was originally identified by homology to the agouti protein, another potent signaling molecule involved in obesity disorders in mice. While AGRP's exact mechanism of action is unknown, it has been identified as a competitive antagonist of melanocortin receptors 3 and 4 (MC3r, MC4r), and MC4r in particular is implicated in the hypothalamic control of feeding behavior. Full length agouti and AGRP are only 25% homologous, however, their active C-terminal regions are approximately 40% homologous, with nine out of the 10 Cys residues spatially conserved. Until now, 3D structures have not been available for either agouti, AGRP or their C-terminal regions. The NMR structure of MARP reported here can be characterized as three major loops, with four of the five disulfide bridges at the base of the structure. Though its fold is well defined, no canonical secondary structure is identified. While previously reported structural models of the C-terminal region of AGRP were attempted based on Cys homology between AGRP and certain toxin proteins, we find that Cys spacing is not sufficient to correctly determine the 3D fold of the molecule.
 ...
PMID:NMR structure of a minimized human agouti related protein prepared by total chemical synthesis. 1037 Nov 51


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