Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiestrogen binding sites (AEBS) were measured in microsomal fractions of 102 malignant breast tumors and 24 nonmalignant breast tissues. The number of AEBS was determined by Scatchard analysis. The cytosol contents of estrogen and progesterone receptors were also analyzed in these tissues. Overall, 50% of the malignant tumors and 33% of the nonmalignant normal breast tissues had detectable contents of AEBS. No correlation was observed between cytosol estrogen receptor (ER) content and microsomal AEBS in the tumors. Detailed data analysis in patients at Stage IV disease revealed that 60% of estrogen receptor positive tumors had no detectable microsomal AEBS contents whereas in the remaining 40% tumors, high affinity AEBS were observed. On the other hand, AEBS were also detected in 35% of ER-poor tumors. Anti-estrogen binding sites were higher in tumors obtained from premenopausal women than in those of postmenopausal women. The incidence of AEBS-positive tumors or AEBS concentration was not influenced by either the patients' obesity or their disease stage.
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PMID:Antiestrogen binding sites in microsomal fractions of malignant and nonmalignant human breast tissues. 359 91

In response to recent studies from India suggesting that malnutrition, as assessed by anthropometric indexes, affects metabolism of oral progestogens, this study administered a mini-pill containing .35 mg of norethindrone (NET) and combination pills containing 250 or 150 mcg of d-norgestrel (d-NG) and either 50 or 30 mcg ethinyl estradiol as a single dose for fasting women of high and low income. Blood samples were collected for up to 24 hours for NET and 80 hours for the combination pills. Pharmacokinetics were evaluated by a least-squares method. Anthropometric measurements were also made. Peak NET levels occurred within 1-2 hours; half-life of plasma NET was shorter among low income, malnourished women compared with high income, well-nourished women. A direct correlation between weight/height and half-life of the drug suggests that malnutrition enhanation rate and reduces NET's half-life. Peak levels for d-NG also were reached between 1 and 2 hours after dosing. In well-nourished women, the decline in plasma d-NG was tri-exponential; malnourished women showed a biphasic curve with a neglible alpha-phase. Therefore, the lower the nutrition status, the faster the plasma clearance of these 2 orally administered compounds. Studies inn rabbits designed to elucidate this connection showed a significant elevation in specific activities of liver microsomal glucuronyl transferase and cytochrome-p450 in undernourished compared with control animals. There was also an increase in the amount (but not affinity) of uterine progesterone receptors in undernourished animals. Another study of a small group of Thai and Indian women showed positive correlation between anthropometric indexes and post peak plasma NET levels; however, an obesity study of Thai women found no such correlation.
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PMID:Influence of nutritional status on pharmacokinetics of contraceptive progestogens. 637 30

Organ-specific autoantibodies (AAb) to thyroid and non-thyroid antigens of various endocrine and exocrine glands (glandular stomach, pancreas, adrenal, parathyroid, and striated muscle) were determined by different serological procedures in sera from Obese strain (OS), Cornell C strain (CS), normal inbred strains (CC and CB), and outbred normal White Leghorn (NWL) chickens. Thyroglobulin autoantibodies (Tg-AAbs), evaluated by immunodiffusion, passive hemagglutination, enzyme-linked immunosorbent assay, and indirect immunofluorescence, as well as other organ-specific AAbs determined by indirect immunofluorescence, predominated in OS chickens. Tg-AAbs were found in the highest frequency, thyroid microsomal AAbs in intermediate frequency, and the other organ-specific AAbs in low frequency in OS chickens. Thyroid and non-thyroid organ-specific AAbs were found only occasionally in control chickens and then only in low titers. Thus, spontaneous autoimmune thyroiditis of OS chickens correlates closely with human Hashimoto thyroiditis not only in respect to AAbs to thyroid antigens but also to nonthyroid organ-specific antigens. Non-organ-specific AAbs, such as antinuclear antibodies, antibodies to chicken red blood cell nuclei, mitochondrial AAbs, smooth muscle antibodies, and reticulin AAbs occur in high frequency in all strains of chickens tested. Even a slight prevalence in NWL chickens was seen, indicating that the abnormal immune response in OS chickens is restricted to organ-specific antigens of the thyroid gland and in some cases also to other exocrine or endocrine glands.
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PMID:Nonthyroid autoantibodies in obese strain (OS) chickens. 642 87

In vivo and in vitro alterations in drug metabolism and the extent of enzyme induction of the hepatic microsomal cytochrome P-450 system were evaluated in obese and lean Zucker and lean Sprague-Dawley rats. Phenobarbital enzyme-inducing regimens were administered p.o. to achieve similar steady-state phenobarbital plasma concentrations. Control rats received p.o. placebo solution. No significant intra- or inter-strain differences in antipyrine clearance (milliliters per hour) or apparent volume of distribution (liters) were observed between the placebo-treated lean Sprague-Dawley, lean Zucker and obese Zucker rats. Intra- and inter-strain differences in hepatic microsomal protein and cytochrome P-450 content were observed. Compared to placebo, antipyrine clearance (milliliters per hour) after chronic phenobarbital pretreatment was increased in the Sprague-Dawley (198%) and lean Zucker rats (131%), but not significantly altered in the obese Zucker rats. Similarly, increases in hepatic weight, whole liver microsomal protein and cytochrome P-450 content were also observed in the Sprague-Dawley (34, 124 and 352%, respectively) and the lean Zucker rats (24, 96 and 249%, respectively). However, no significant alterations in these parameters were observed in the obese Zucker rats after phenobarbital treatment. Results from these in vivo and in vitro studies implicate alterations in drug metabolism and genetic differences in cytochrome P-450 content in Zucker rats relative to the Sprague-Dawley strain. Obese Zucker rats failed to exhibit a significant induction response after phenobarbital pretreatment.
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PMID:Phenobarbital in the genetically obese Zucker rat. II. In vivo and in vitro assessments of microsomal enzyme induction. 650 19

The effects of increasing cell size on glucose transport activity and metabolism and on the concentrations of glucose transport systems in both the plasma and low density microsomal membranes in isolated adipose cells from the aging rat model of obesity have been examined. Glucose transport activity was assessed by measuring l-arabinose transport and the concentration of glucose transport systems estimated by measuring specific d-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity increases from 0.3 to 1.4 fmol/cell/min with a 10-fold increase in cell size, but remains constant per unit cellular surface area and is accompanied by a constant 5 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. Maximally insulin-stimulated glucose transport activity, on the other hand, remains constant at 2.3 fmol/cell per min with increasing cell size, but markedly decreases per unit cellular surface area and is accompanied by a decrease from 30 pmol of glucose transport systems/mg of plasma membrane protein to the basal level. These diminished effects of insulin on glucose transport activity and the number of glucose transport systems in the plasma membrane fraction in enlarged cells are paralleled by an 80% decrease in the basal number of glucose transport systems/mg of membrane protein in the low density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. The effects of cell size on the metabolism of a low concentration of [1-(14)C]glucose (0.56 mM) directly parallel those on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction, and are not associated with significant alterations in the cell's sensitivity to insulin. Thus, adipose cellular enlargement is accompanied by the development of a marked "insulin resistance" at the glucose transport level, which may be the consequence of a relative depletion of glucose transport systems in the intracellular pool.
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PMID:Mechanism of insulin-resistant glucose transport activity in the enlarged adipose cell of the aged, obese rat. 674 3

Mice were found to convert acetone to lactate at appreciable rates. The conversion of acetone to gluconeogenic precursors could provide additional glycolytic intermediates that would allow the more complete utilization of lipid stores and increase survival time during starvation. In mice that were starved for 3 days or were provided with acetone in the drinking water the acetone-metabolizing pathway was induced to levels severalfold normal. Mice heterozygous for obesity-producing mutations, either obese (ob/+) or diabetes (db/+), showed induction of the activity of this pathway to a significantly higher degree than did homozygous normal (+/+) mice of the same strain. This more effective conversion of acetone to lactate exhibited by heterozygous mice could account for their prolonged survival on a starvation regimen compared to that of normal homozygotes. The rate-limiting step in the pathway appears to be the conversion of acetone to a hydroxylated derivative. The enzyme system effecting this conversion is an NADPH-requiring microsomal oxygenase found in the liver.
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PMID:Acetone metabolism in mice: increased activity in mice heterozygous for obesity genes. 692 21

Obesity is often associated with an elevated total body cholesterol synthesis. In order to evaluate the role of hepatic cholesterogenesis in this phenomenon, we assayed the rate-limiting step in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in the microsomal fraction of liver biopsies obtained operatively from ten morbidly obese (relative body weight greater than 155%) subjects. Eighteen normal-weight patients (relative body weight less than 120%) with cholesterol gallstones served as controls. Hepatic HMG CoA reductase activity, expressed as pmol X min-1 X mg protein-1, was 60% higher in the obese subjects compared to the gallstone patients (P less than 0.05). Microsomal protein concentration was lower in the obese patients, so that enzyme activity calculated per gram liver was not significantly different between the two groups. However, mevalonate formation, expressed in terms of total organ activity, was higher in the obese than in the nonobese group. The results suggest that the liver is a major contributor to the increased cholesterol production seen in obesity.
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PMID:Hepatic cholesterol metabolism in obesity: activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase. 711 74

This study was designed to examine whether n-3 and n-6 polyunsaturated fatty acids at a very low dietary level (about 0.2%) would alter liver activities in respect to fatty acid oxidation. Obese Zucker rats were used because of their low level of fatty acid oxidation, which would make increases easier to detect. Zucker rats were fed diets containing different oil mixtures (5%, w/w) with the same ratio of n-6/n-3 fatty acids supplied either as fish oil or arachidonic acid concentrate. Decreased hepatic triacylglycerol levels were observed only with the diet containing fish oil. In mitochondrial outer membranes, which support carnitine palmitoyltransferase I activity, cholesterol content was similar for all diets, while the percentage of 22:6n-3 and 20:4n-6 in phospholipids was enhanced about by 6 and 3% with the diets containing fish oil and arachidonic acid, respectively. With the fish oil diet, the only difference found in activities related to fatty acid oxidation was the lower sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition. With the diet containing arachidonic acid, peroxisomal fatty acid oxidation and carnitine palmitoyltransferase I activity were markedly depressed. Compared with the control diet, the diets enriched in fish oil and in arachidonic acid gave rise to a higher specific activity of aryl-ester hydrolase in microsomal fractions. We suggest that slight changes in composition of n-3 or n-6 polyunsaturated fatty acids in mitochondrial outer membranes may alter carnitine palmitoyltransferase I activity.
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PMID:Effect of dietary n-3 and n-6 polyunsaturated fatty acids on lipid-metabolizing enzymes in obese rat liver. 796 69

We investigated glucose transporters (GLUT 1 and GLUT 4) in subcellular membrane fractions of white adipose tissue (WAT) of insulin-resistant obese aurothioglucose (AuTG)- or monosodium glutamate (MSG)-treated mice. In vivo insulin stimulation (0.75 U/kg, EV) promoted, 10 min later, no significant change on glycemia of both AuTG and MSG obese mice, but control mice showed a decrease of 30% (p < 0.001). Basal GLUT 4 content in WAT of obese mice was reduced by 40% (p < 0.001) when compared to that of nonobese mice. Insulin-stimulated GLUT 4 content was significantly (p < 0.01) higher in plasma membrane fraction and lower in microsomal fraction when compared to respective basal values, in all groups. Although the absolute values of GLUT 4 were lower in membrane fractions of obese mice, the relative changes stimulated by insulin were similar among the groups. No effect of obesity or insulin stimulation was observed upon GLUT 1 content. We conclude that WAT of insulin-resistant obese AuTG- and MSG-treated mice has a decreased GLUT 4, but not GLUT 1, content, and the in vivo insulin-stimulated GLUT 4 translocation is preserved.
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PMID:Reduced content and preserved translocation of glucose transporter (GLUT 4) in white adipose tissue of obese mice. 819 Jul 86

We assessed the content of two isoforms of glucose transporter (GLUT 1 and GLUT 4) in insulin-sensitive tissues of hypothalamic obese mice treated with either aurothioglucose (AuTG) or monosodium glutamate (MSG). The animals were studied when obesity had reached a plateau, and they were clearly insulin resistant. We studied different membrane fractions from white adipose tissue (WAT), such as fat-free extract (FFE), plasma membrane (PM) and microsomal (M) fractions. GLUT 4 expressed per protein content displayed a decrease of 50% (p < 0.001) in all membrane fractions of AuTG- and MSG-treated mice. The PM GLUT 4 content, expressed per cell surface area, was reduced by 70% (p < 0.001) in obese mice, and the total FFE GLUT 4, expressed per total fat mass, was 5 times reduced in obese mice. Compared to control mice, obese mice showed a reduction (p < 0.01) of the GLUT 4 amount by 30% (AuTG) and by 40% (MSG) in total membrane fraction (TM) of skeletal and cardiac muscles. Similarly, a reduction of the GLUT 4 amount by 40% (AuTG) and by 45% (MSG) in FFE of brown adipose tissue was observed. The GLUT 1 content in FFE of WAT and TM of skeletal muscle showed no significant difference among the different animal groups. These results confirm a decreased expression of GLUT 4, but not of GLUT 1, in insulin-sensitive tissues, which may contribute to the impaired glucose utilization in these obese animals.
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PMID:Decreased glucose transporter (GLUT 4) content in insulin-sensitive tissues of obese aurothioglucose- and monosodium glutamate-treated mice. 822 98


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