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)

Diabetes mellitus occurs in many animals species. However, only a few have been utilized in systematic studies designed to answer unsolved problems associated with the disorder in man such as molecular basis, pathogenesis of the vascular and neural lesions, and the roles of diet, exercise and obesity. Among the animal models available, rodents have been studied most thoroughly for a number of reasons: a) short generation time (sexually mature at about 3 mo of age, gestation time 21 days) and life-span is approximately 3 yr; b) hyperglycemia and/or obesity is known to be inherited in several species; c) environmental factors can be controlled easily in the laboratory because of small size; and d) economic considerations. The better-known rodent diabetes/obesity syndromes may be categorized as follows: 1) hyperglycemic with ketoacidosis, nonobese (Chinese hamster, South African hamster); 2) hyperglycemic with insulin hypersecretion, moderate obesity and may develop ketoacidosis (diabetic mouse (db/db), spiny mouse, sand rat); and 3) less pronounced hyperglycemia with hyperinsulinemia, insulin "resistance" and marked obesity (obese (ob/ob), yellow (Ay) and New Zealand obese (NZO) mice, and the Zucker "fatty" rat). The PBB/Ld mouse, described here in detail for the first time, is a new strain of mouse that also fits into the latter category. Members of this strain following maturity develop an obesity that is characterized by increasing cellularity of adipose tissue, increased serum immunoreactive insulin, reduced glucose tolerance, fatty liver, and hyperlipidemia. Therefore, this strain of mouse represents another model for study of adult onset obesity.
 ...
PMID:Animal models of diabetes and obesity, including the PBB/Ld mouse. 77 Jan 97

The autosomal recessive mutations fa (rat) and db (mouse) cause obesity syndromes that develop early and ultimately become severe. Although both fa/fa rats and db/db mice have been studied extensively as models of human obesity and diabetes, the molecular bases of these phenotypes remain unknown. We have mapped fa in 50 fa/fa (obese) offspring of a (13M x Brown Norway) F1 fa/+ intercross relative to two molecular markers, Ifa and Glut-1, which flank db on mouse chromosome 4 and which are located on rat chromosome 5. Ifa and Glut-1 are linked to fa, with a gene order, Ifa-fa-Glut-1, that is identical to that for the region around db in the mouse genome. These results place fa on rat chromosome 5 and suggest that db and fa are mutations in homologous genes.
 ...
PMID:Rat obesity gene fatty (fa) maps to chromosome 5: evidence for homology with the mouse gene diabetes (db). 188 16

Administration of monosodium glutamate (MSG) to neonatal rodents produces permanent lesions of hypothalamic arcuate neurons that secrete GH-releasing hormone (GHRH). The present study was intended to determine the consequences of GHRH deficiency on the pulsatile GH secretory pattern and growth in MSG-treated female rats and to compare these effects with those observed in male littermates. Male and female rats were injected with MSG [4 mg/g body wt (BW), sc] or saline (controls) on days 2, 4, 6, 8, and 10 after birth. Immunoreactive GHRH concentrations were decreased in the hypothalamus (by 60%) and in the median eminence (by 95%) of adult male and female MSG-treated rats. In contrast, somatostatin concentrations were unaffected. BW and linear growth were severely impaired in male MSG-treated rats, but in MSG-lesioned females BW was not different from controls, and the attenuation of longitudinal growth was less severe and the obesity more pronounced than in males. These sex differences occurred despite similar reductions (by 55%) in serum insulin-like growth factor I concentrations in male and female MSG-treated rats. MSG treatment also produced decreases in pituitary wt and GH content (by 60%), independent of sex. Pulsatile GH secretion was studied by serial blood sampling of chronically cannulated, freely moving rats. Plasma GH patterns were analyzed by the PULSAR program. Compared to controls, treatment with MSG led to a marked inhibition (by 90%) of GH secretion in both sexes. Significant reductions in GH pulse amplitude (-95%) and pulse duration (-62%) were observed in males, whereas pulse amplitude (-85%), pulse frequency (-67%), and baseline GH concentrations (-80%) were markedly reduced in females. The GH responses to an iv bolus injection of rat GHRH (1 microgram/rat) was severely blunted in both male and female MSG-treated rats. This study demonstrates that GHRH deficiency in female rats results in a marked inhibition of GH pulses, as in males, but also causes severe and sex-specific reductions in GH basal secretion and pulse frequency. These observations suggest that hypothalamic GHRH secretion in female rats is more continuous than in males and is a determinant of the elevated interpulse secretion of GH. Moreover, body wt and linear growth are less severely affected by arcuate lesions in female animals, compared to males. These sex-related differences in growth rates may result in part from the tendency of female MSG-lesioned rats to become more obese than males, and the development of obesity, in turn, may antagonize the factors that tend to slow linear growth.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neonatal treatment with monosodium glutamate: effects of prolonged growth hormone (GH)-releasing hormone deficiency on pulsatile GH secretion and growth in female rats. 198 48

Injections of monosodium glutamate to neonate rats induce chronic growth hormone deficiency by hypothalamic lesions in the regions of the nucleus arcuatus and the eminentia mediana. The glutamate treated rats develop massive obesity. By this type of obesity hyperinsulinemia in the dynamic phase is not evident. The adipose tissue of the GOR (glutamate obese rat) is characterized by hypertrophic adipocytes and diminished number of adipocytes. In the GOR glucose oxidation and glucose lipid conversion are increased, but insulin sensitivity of glucose metabolism is diminished. The enhanced glucose utilization in adipose tissue of the GOR is discussed as being the consequence of the chronic growth hormone deficiency.
 ...
PMID:[Glucose utilization in adipose tissue of rats in chronic somatotropin deficiency]. 267 26

The deoxyribonucleic acid (DNA) is constant per cell in diploid tissues and in polyploid tissues the DNA content and the cytoplasm increase commensurately. In muscle the DNA unit (protein/DNA) was described on the assumption that each nucleus has jurisdiction over a certain volume of cytoplasm. Such an approach allows a sensible interpretation of metabolic data. Since 66-70% of nuclei are within myofibres muscle represents a reasonably homogeneous tissue. A brief historical review is made concerning the use of DNA as a cell constant. The application of this knowledge to normal human somatic growth and to disease states is considered as well as reduced nutrition and overnutrition. The consequences of reduced nutrition as it related to brain growth are briefly mentioned as is our 7 year study on the fetal primate (Macaca mulatta). Attention is focussed on our work in the early 1960's concerning the role of insulin and growth hormone on the DNA unit. In the last decade this work culminated in the close study of the Little Mouse with isolated growth hormone deficiency--thus exposing the panhypopituitary model (the human pituitary dwarf, Snell Smith mouse or hypophysectomised rat) as non-optimal models. The findings indicate that growth hormone is indeed related to cell replication and insulin to cytoplasmic growth in the postnatal period but the role of other hormones is clearly important, augmenting or opposing these hormones. The concept of constant change of the DNA unit not only applies to major tissues such as muscle but to the study of kidney growth when the contralateral kidney is removed (renal compensatory growth). Species differences are noted in the pattern of cell growth in muscle, but emphasis is placed on cell replication rather than on cytoplasmic growth in the primate. Restriction of protein energy metabolism mainly affects cytoplasmic growth of muscle but restoration of growth to expected levels is the rule. Overnutrition and obesity relate to excessive growth of DNA units in number rather than size. Attention is drawn to factors other than calories, proteins and hormones that influence hormonal actions viz. trace metals such as zinc, chromium and vanadium. The cell mass of the body can readily be reached by relatively non-invasive methods and by monitoring the intracellular water. Muscle mass can be precisely measured by creatinine excretion. The cell mass of muscle constitutes 70% of the entire cell mass.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The control of cell mass and replication. The DNA unit--a personal 20-year study. 391 56

The relationships among food intake, insulin secretion, and adrenocortical function are reviewed. It is hypothesized that a major role of structures in, or passing through, the ventromedial hypothalamus is to inhibit food intake, insulin secretion, and adrenocortical function during the day (in the nocturnally active rat) and that this activity is normally driven by elements within the suprachiasmatic nuclei. Lesions of the ventromedial hypothalamus of rats result in nonrhythmic food intake, hyperinsulinemia, nonrhythmic adrenocortical function, and obesity. Adrenalectomy prevents or reverses the effects of lesions of the ventromedial hypothalamus on food intake, insulin secretion, and obesity, and corticosteroid replacement restores them. Because the actions of corticosteroids are both time- and dose-dependent, it is proposed that the effects of the tonic levels of corticosteroids observed after lesions of the ventromedial hypothalamus are to augment the hyperphagia, hyperinsulinemia, and substrate flow into fat to a greater extent than would occur if there were a normal circadian rhythm in adrenocortical function.
 ...
PMID:Viewing the ventromedial hypothalamus from the adrenal gland. 632 Jun 67

An anorectic substance in human, mammalian (rat, guinea pig, rabbit, cat, dog, horse, cattle) and poultry (goose) serum, named satietin, was discovered recently. The substance was extracted and purified by gelchromatographic techniques. With an improved technique, a highly purified glycopeptide fraction, containing 87% carbohydrates (fucose, mannose, glucose and galactose) and 12.5% amino acids, was prepared from human serum and its anorectic effect was measured in fasting rats. A biological assay for satietin, expressing activity in units, was developed. The unit is equivalent to the anorectic activity of the amount of a sample which, when given intracerebroventricularly (icvtr) decreases the chow pellet consumption of rats deprived of food for 96 h, during the first day of feeding, from 24.04 +/- 0.76 g to 10 g. With higher icvtr doses of satietin (2-3 units/rat) the 24 h consumption of the fasting rats can be reduced below 4-5 g and the animals begin to eat on the second day of feeding only. With samples containing 100 units/mg, the anorectic effect was checked at various routes of administration. Satietin acts icvtr, proving that its site of effect is in the brain. A significant decrease in food intake was also observed in the deprived rats 1 h after the oral administration of satietin (100 units/100 g), 1 h after the intravenous or subcutaneous administration of satietin (40 units/100 g), the first hour consumption of food was completely blocked. The anorectic effect of satietin was compared to the endogenous peptides (CCK, calcitonin, pGlu-His-GlyOH), proved or claimed to have anorectic effect, and to the drug-pair, amphetamine and fenfluramine, which represent the two main types of anti-obesity agents. Satietin proved to be a highly specific anorectic substance different in its spectrum from hitherto known compounds inhibiting food intake.
 ...
PMID:Satietin: a centrally acting potent anorectic substance with a long-lasting effect in human and mammalian blood. 716 20

Very-low-calorie diets lower blood pressure acutely in obese humans and rats. However, refeeding after dietary restriction produces mild hypertension in rats. Refeeding hypertension was characterized in genetically obese spontaneously hypertensive rats (obese SHR, Koletsky rat), a model of genetic obesity and hypertension. Obese SHR were fed a restricted diet (Optifast) for 12 days, refed ad libitum for 28 days, dieted again for 12 days, and then refed 4 days and killed. Control obese SHR and lean SHR littermates were fed ad libitum continuously. Dietary restriction led to rapid weight loss followed by prompt regain to baseline weight after return to unrestricted food intake. Heart rate fell with institution of the low-calorie diet and returned to baseline on refeeding. Blood pressure became elevated during refeeding in dieted obese SHR relative to ad libitum fed obese SHR controls. The fall in blood pressure after ganglionic blockade with chlorisondamine was exaggerated in refed obese SHR, and cardiac beta-adrenergic receptors were downregulated. Both of these findings imply increased sympathetic tone. The left ventricular wall was thicker in the refed obese SHR than in the ad libitum fed obese SHR. Shorter cycles of weight loss and regain in lean SHR led to transient increases in blood pressure and heart rate. Cycles of dietary restriction and refeeding in obese SHR elicit sustained blood pressure elevation via sympathetic activation and exacerbate cardiac hypertrophy. Drastic fluctuations in nutrient intake may not be advantageous in hypertension.
 ...
PMID:Refeeding hypertension in obese spontaneously hypertensive rats. 799 26

The obese Zucker rat is an animal model of genetically inherited obesity demonstrating remarkable hyperphagia. In the present study, to try to clarify the relationship between obesity and gastric function including gastric mucosal integrity, the gastric acid secretion, emptying, and mucosal resistance against ulcerogenic agents were compared in lean and obese Zucker rats. Male lean and obese Zucker rats were housed at 25 degrees C under 12-hr/12-hr lighting cycle (on at 7:00 AM). The gastric acid output of obese Zucker rats was markedly smaller than that of lean Zucker rats, whereas there was no significant difference in gastric emptying in both groups. The degree of mucosal lesion formation induced by ulcerogenic agents was assessed by measuring the total length of all mucosal lesions observed (ulcer index; mm). The intragastric administration of indomethacin (20 mg/kg) produced hemorrhagic mucosal lesions in both lean and obese groups of Zucker rats, but the ulcer index was remarkably smaller in obese Zucker rats than that of their lean littermates (5.2 +/- 1.2 mm vs. 17.5 +/- 3.5 mm, mean +/- SEM, P < 0.01). In addition obese Zucker rats exhibited stronger resistance against the intragastric challenge of absolute ethanol (1 ml/rat), a necrotizing agent, with its ulcer index being 8.5 +/- 2.7 mm, compared with lean Zucker rats whose ulcer index was 26.4 +/- 5.4 mm (P < 0.01). The bilateral subdiaphragmatic vagotomy decreased both gastric acid secretion and the ulcer index of indomethacin-induced gastric injury observed in both obese and lean Zucker rats, whereas there was no significant difference in the ulcer index of ethanol-induced gastric injury. These results suggest that obese Zucker rats exhibit enhanced resistance against ulcerogens and decreased acid output. It is also speculated that the vagal system might be involved in inhibition of acid secretion and formation of indomethacin ulcers in obese Zucker rats.
 ...
PMID:[Pathophysiological study on the mucosal defense system of genetically obese Zucker rats]. 899 42

To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH-lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH-lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single i.v. (1.0 mg/rat) or intracerebroventricular (2.0 micrograms/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH-lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.
 ...
PMID:Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: evidence for loss of its satiety effect in VMH-lesioned rats. 904 94


1 2 3 4 Next >>