UMLS:C0028754 - FACTA Search

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)

The treatment of obesity is one of the major measures available today in the field of preventive medicine. In particular, the coronary epidemic of Western civilisation would be halted, and most cases of maturity-onset diabetes prevented, if obesity were to be treated effectively. Anorectic drugs act mainly on the satiety centre in the hypothalamus to produce anorexia. They also have various metabolic effects involving fat and carbohydrate metabolism, but many of these may be secondary to loss of weight. Most of the drugs are related directly or indirectly to amphetamine and in addition act by increasing general physical activity. Anorectic drugs tend to lose their effect after some months, and part of this reduction in effect may be due to chemical alterations produced by the drugs in the brain. All the drugs, with the exception of fenfluramine, have a stimulant effect on the central nervous system in some individuals, resulting in restlessness and nervousness, irritability and insomnia. Fenfluramine commonly produces drowsiness in normal doses, but has stimulant effects with overdosage. Dexamphetamine, phenmetrazine and benzphetamine all tend to cause euphoria and the risk of addiction is therefore considerable. Euphoria occasionally occurs with diethylpropion, phentermine and chlorphentermine, but to a much lesser extent. Side-effects also occur due to sympathetic stimulation and gastro-intestinal irritation. These side-effects may cause some individuals to stop taking the drug, but are never serious or dangerous. Drug interactions may occur with monoamine oxidase inhibitors and to a clinically unimportant extent, with antihypertensive drugs. The anorectic drugs have a very definite part to play in the treatment of obesity, mainly for those individuals who have altered their eating habits but have come to a plateau of weight which they find difficult to get below. The drugs are best given in a long-acting form and can safely be continued as long as weight loss persists, provided that the clinician exercises careful supervision. Dexamphetamine, phenmetrazine and benzphetamine should rarely be used because of the danger of addiction, and chlorphentermine is potentially hazardous for long-term use. Diethylpropion emerges as the drug of first choice, as fenfluramine has a tendency to cause depression and has a higher incidence of side-effects. Fenfluramine is mainly useful for people who are especially tense and for obese maturity-onset diabetics who have been unable to lose weight with the biguanides. Mazindol and phentermine appear to be useful as alternative drugs.
...
PMID:Anorectic drugs: use in general practice. 78 35

Obesity is a major risk factor for cardiovascular disease. However, a direct link between these two states is difficult to establish, since obesity frequently occurs with other disease states such as diabetes, hypertension and atherosclerosis. Clinical studies have clearly shown that uncorrected obesity is associated with cardiac hypertrophy and compromised ventricular function. A number of rodent models of obesity have been studied in terms of cardiovascular adaptations. Cardiac function of the obese Zucker rat appears to be normal at a younger age. Only after several months is depression in cardiac function discernable. These animals are mildly hypertensive, but do not exhibit the characteristic increase in cardiac output associated with human obesity. A unique characteristic of JCR:LA-cp rat is that they develop atherosclerotic and myocardial lesions. Hearts from these animals will maintain normal function when perfused with physiological levels of calcium. At higher calcium concentrations, however, mechanical function becomes impaired. Dietary-induced obese rats exhibit many of the hemodynamic alterations associated with human obesity, but there is no evidence to-date that these animals will develop severe cardiac depression. Short-term weight reduction apparently has beneficial cardiovascular effects, but weight cycling may be harmful. Given the widespread occurrence of obesity, further studies are warranted to characterize the cardiac manifestations of this condition.
...
PMID:Cardiovascular abnormalities associated with human and rodent obesity. 143 63

The present study investigated whether differences in maternal NaCl intake altered 1) maternal-pup behavior and 2) the development of dietary obesity and blood pressure level of adult Sprague-Dawley rats maintained on a palatable high-fat/milk (HF/M) diet. Thirteen dams fed high (3%) NaCl and 12 dams fed basal (0.12%) NaCl were observed on postnatal days 2-21 for differences in the number of times spent 1) nursing, 2) in contact with or licking, sniffing, and carrying pups, and 3) in nest building. The offspring were continued on their respective NaCl diets to 30 days postpartum, and then both NaCl groups were fed an intermediate (1%) NaCl diet thereafter. Beginning at 60 days of age, the offspring from each maternal NaCl condition were fed either Agway R-M-H 1000 pelleted food or a HF/M diet for 14 wk. Dams fed 3% NaCl spent significantly more time licking their pups than did dams fed 0.12% NaCl. The adult offspring of dams fed 3% NaCl had a significantly higher level of systolic blood pressure and consumed more calories of sweetened condensed milk on the HF/M diet than did rats raised on 0.12% NaCl. Dietary-induced obesity did not magnify the increase in systolic blood pressure from high maternal NaCl intake. The present results raise the possibility that increased maternal licking may contribute to the increased blood pressure and solution intake that follows from high maternal NaCl intake.
...
PMID:High NaCl intake of rat dams alters maternal behavior and elevates blood pressure of adult offspring. 844 85

Capillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male rat, which exhibits the metabolic syndrome of obesity, insulin resistance, hyperlipidemia, and hyperinsulinemia. Lean littermates that did not develop these alterations served as controls. Animals of both groups were normotensive (mean arterial pressure 136+/-2 mmHg). Hearts from obese and lean rats aged 7 (n = 6) or 18 (n = 8) weeks were perfused in vitro at 10 ml/min per gram wet wt over 51 min with Krebs-Henseleit buffer containing 0.1 or 0.5 U human insulin/l (equivalent to 0.6 and 3 nmol/l). Interstitial fluid was collected using a validated method, and interstitial insulin was determined with a radioimmunoassay. At 0.1 U/l, insulin transfer velocity was similar in both experimental groups (half-times of transfer: 11+/-0.2 min in obese and 18+/-4 min in lean rats; NS), but at 0.5 U/l, the respective half-times were 7+/-1 min in lean and 13+/-2 min in obese rats (P < 0.05). The steady-state level of insulin in the interstitium was 34+/-1% of the vascular level at 0.1 U/l and reached the vascular level (102+/-2%) at 0.5 U/l in both lean and obese rats. In rats aged 18 weeks, the half-times of insulin transfer were 31+/-2 and 14+/-l min in obese rats and 10+/-0.3 and 7+/-0.3 min in lean rats (P < 0.05). Again, interstitial steady-state levels were similar in both groups. Finally, postprandial insulin dynamics were simulated over a period of 120 min with a peak concentration of 0.8 U/l in rats aged 27 weeks (n = 4). The maximal interstitial level was 0.38+/-0.02 U/l in lean rats and 0.24+/-0.02 U/l in obese rats (P < 0.05), and a similar difference was noted throughout insulin infusion (areas under the transudate concentration-time curves: 17 and 11 U/min per 1, respectively). These data show, for the first time in a genetic animal model of insulin resistance, that transfer of insulin across the endothelium is substantially delayed in obese insulin-resistant rats and that it likely contributes to the postprandial alterations of glucose metabolism observed in the metabolic syndrome.
...
PMID:Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats. 1090 90

Rats fed a high-fat diet before and during lactation have difficulty initiating lactation and have high pup mortality rates, low milk production and, consequently, poor pup growth. To determine if these adverse outcomes can be mitigated with dietary changes made after delivery, obese Sprague-Dawley rats (who had previously been fed a high-fat diet [AIN-93M, modified to contain 35% fat, w/w]) were assigned at parturition to continue to be fed this diet (HF) or switched to free access to a corresponding low-fat (LF) diet (AIN-93M, 4% fat w/w) or switched to the LF diet and restricted to consuming only 75% of ad libitum intake (LF/R). Dams lost weight during lactation, but weight loss was much less in the LF group (19g) than in the other two groups (47 and 59g, HF and LF/R, respectively). There was no appreciable change in body water; body fat decreased by about half in all groups, but most substantially in the LF/R group. Compared with the HF group, milk production was 50% higher in the LF group and 12% lower in the LF/R group. Milk lipid concentration tended to be higher and milk water concentration lower in the HF compared with the other two groups. Growth of the litters of the LF dams was significantly higher than both HF and LF/R dams. These results indicate that switching to a low-fat diet mitigates the negative effects of obesity and continued high-fat feeding on lactational performance and pup growth. Consumption of restricted quantities of a low-fat diet negatively affected milk production and failed to improve pup growth, despite the dams' mobilization of body fat in support of lactation.
...
PMID:A low-fat diet but not food restriction improves lactational performance in obese rats. 1178 70

Insulin-resistant muscle tissue contains low proportions of arachidonic acid (AA), and increased proportions of muscle AA correlate with improved insulin sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long-chain fatty acids (FA) have been named the "one true" endogenous ligand for activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has been named a "good candidate" as a naturally occurring indirect activator of PPAR. This study was conducted to determine DHEA's effects on lipid profiles of skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long-chain FA profiles in muscle tissue of obese rats such that they more closely resemble that of the lean. In our experiments, we employed a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average daily calories consumed by their corresponding treatment group. Hearts and gastrocnemius muscles were assayed for phospholipid (PL), free FA, and triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater in both muscle types of lean compared to obese rats. Hearts from both DHEA groups had greater PL proportions of AA and less oleic (18:1) acid than their PF controls. Likewise, 18:1 proportions were significantly lower in the gastrocnemius; however, AA proportions were not significantly different. Similar phenotypic profile differences were observed in the TG fraction of both muscle types. There were no DHEA-related TG FA profile alterations.
...
PMID:Dehydroepiandrosterone alters phospholipid profiles in Zucker rat muscle tissue. 1183 92

Obesity is associated with risk factors for cardiovascular disease, including insulin resistance, and can lead to cardiac hypertrophy and congestive heart failure. Here, we used the insulin-sensitizing agent rosiglitazone to investigate the cellular mechanisms linking insulin resistance in the obese Zucker rat heart with increased susceptibility to ischemic injury. Rats were treated for 7 or 14 days with 3 mg/kg per os rosiglitazone. Hearts were isolated and perfused before and during insulin stimulation or during 32 min low-flow ischemia at 0.3 ml small middle dot min(-1) small middle dot grams wet wt(-1) and reperfusion. D[2-(3)H]glucose was used as a tracer of glucose uptake, and phosphorus-31 nuclear magnetic resonance spectroscopy was used to follow energetics during ischemia. At 12 months of age, obese rat hearts were insulin resistant with decreased GLUT4 protein expression. During ischemia, glucose uptake was lower and depletion of ATP was greater in obese rat hearts, thereby significantly impairing recovery of contractile function during reperfusion. Rosiglitazone treatment normalized the insulin resistance and restored GLUT4 protein levels in obese rat hearts. Glucose uptake during ischemia was also normalized by rosiglitazone treatment, thereby preventing the greater loss of ATP and restoring recovery of contractile function to that of lean rat hearts. We conclude that rosiglitazone treatment, by normalizing glucose uptake, protected obese rat hearts from ischemic injury.
...
PMID:Thiazolidinedione treatment normalizes insulin resistance and ischemic injury in the zucker Fatty rat heart. 1191 33

Lipid accumulation is associated with cardiac dysfunction in diabetes and obesity. Transgenic mice expressing non-transferable lipoprotein lipase (LpL) with a glycosylated phosphatidyl-inositol (GPI) anchor in cardiomyocytes have dilated cardiomyopathy. However, the mechanisms responsible for lipid accumulation and cardiomyopathy are not clear. Hearts from 3-month-old mice expressing GPI-anchored human LpL (hLpLGPI) mice had increased fatty acid oxidation and heart failure genes and decreased glucose transporter genes. 6-month-old mice had increased mRNA expression and activation of the apoptosis marker caspase-3. Moreover, hLpLGPI hearts had significant cytochrome c release from mitochondria to cytosol. Low density lipoprotein uptake was greater in hLpLGPI hearts, and this was associated with more intracellular apolipoprotein B (apoB). To test whether lipid accumulation in the hLpLGPI heart is reduced by cardiac expression of apoB, hLpLGPI mice were bred with transgenic human apoB (HuB)-expressing mice. Hearts of HuB/hLpLGPI mice had less triglyceride (38%) and free fatty acids (19%), secreted more apoB, and expressed less atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and more glucose transporter 4 (GLUT4). The increased mortality of the mice was abrogated by the transgenic expression of apoB. Therefore, we hypothesize that cardiac apoB expression improves cardiomyopathy by increasing lipid resecretion from the heart.
...
PMID:Apolipoprotein B production reduces lipotoxic cardiomyopathy: studies in heart-specific lipoprotein lipase transgenic mouse. 1463 11

BACKGROUND: The assumption that lifestyles formed early in life track into adulthood has been used to justify the targeting of health promotion programmes towards children and adolescents. The aim of the current study was to use data from the Northern Ireland Young Hearts Project to ascertain the extent of tracking, between adolescence and young adulthood, of physical activity, aerobic fitness, selected anthropometric variables, and diet. METHODS: Males (n 245) and females (n 231) were assessed at age 15 y, and again in young adulthood [mean (SD) age 22 (1.6) y]. At both timepoints, height, weight and skinfold thicknesses were measured, and physical activity and diet were assessed by questionnaire and diet history method respectively. At 15y, fitness was assessed using the 20 metre shuttle run, while at young adulthood, the PWC170 cycle ergometer test was used. For each measurement made at 15y, subjects were ranked into 'low' (L1; lowest 25%), 'medium' (M1; middle 50%) or 'high' (H1; highest 25%) categories. At young adulthood, similar categories (L2, M2, H2) were created. The extent of tracking of each variable over time was calculated using 3 x 3 matrices constructed using these two sets of categories, and summarised using kappa (kappa) statistics. RESULTS: Tracking of diet and fitness was poor (kappa </= 0.20) in both sexes, indicating substantial drift of subjects between the low, medium and high categories over time. The tracking of physical activity in males was fair (kappa 0.202), but was poor in females (kappa 0.021). In contrast, anthropometric variables such as weight, body mass index and sum of skinfolds tracked more strongly in females (kappa 0.540, kappa 0.307, kappa 0.357 respectively) than in males (kappa 0.337, kappa 0.199, kappa 0.216 respectively). CONCLUSIONS: The poor tracking of fitness and diet in both sexes, and physical activity in females, suggests that these aspects of adolescent lifestyle are unlikely to be predictive of behaviours in young adulthood. In contrast, the fair to moderate tracking of anthropometric variables, particularly in females, suggests that attempts to reduce the ever increasing incidence of overweight and obesity in adults, should probably begin in earlier life.
...
PMID:Tracking of physical activity, fitness, body composition and diet from adolescence to young adulthood: The Young Hearts Project, Northern Ireland. 1546 76

The metabolic phenotype of hearts has been investigated using rodent models of type 2 diabetes which exhibit obesity and insulin resistance: db/db and ob/ob mice, and Zucker fatty and ZDF rats. In general, cardiac fatty acid (FA) utilization is enhanced in type 2 diabetic hearts, with increased rates of FA oxidation (db/db, ob/ob and ZDF models) and increased FA esterification into cellular triacylglycerols (db/db hearts). Hearts from db/db and ob/ob mice and ZDF rat hearts all have elevated levels of myocardial triacylglycerols, consistent with enhanced FA utilization. A number of mechanisms may be responsible for enhanced FA utilization in type 2 diabetic hearts: (i) increased FA uptake into cardiac myocytes and into mitochondria; (ii) altered mitochondrial function, with up-regulation of uncoupling proteins; and (iii) stimulation of peroxisome proliferator-activated receptor-alpha. Enhanced cardiac FA utilization in rodent type 2 diabetic models is associated with reduced cardiac contractile function, perhaps as a consequence of lipotoxicity and/or reduced cardiac efficiency. Similar results have been obtained with human type 2 diabetic hearts, suggesting that pharmacological interventions that can reduce cardiac FA utilization may have beneficial effects on contractile function.
...
PMID:Fatty acid metabolism is enhanced in type 2 diabetic hearts. 1590 68

1 2 3 4 5 6 7 Next >>