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)

The objective was to assess the effect of a new, highly selective beta 3-adrenergic agonist, CL-316,243 (CL) (J. D. Bloom, M. D. Dutia, B. D. Johnson, A. Wissner, M. G. Burns, E. E. Largis, J. A. Dolan, and T. H. Claus., J. Med. Chem. 35: 3081, 1992), on energy balance and brown and white adipose tissues (BAT and WAT, respectively) in young rats eating a high-fat diet to induce obesity. Chronic treatment with CL increased body temperature and 24-h energy expenditure, mainly by increasing resting metabolic rate. Food intake was not altered but carcass fat was reduced. Interscapular BAT was markedly hypertrophied, with three- to fourfold increases in the content of uncoupling protein (UCP) and cytochrome oxidase. Quantitative immunoelectron microscopy of interscapular BAT of CL-treated rats showed smaller mitochondria with an unchanged total amount of UCP per mitochondrion. The relative frequency of the four major cell types in BAT (mature brown adipocytes, preadipocytes, interstitial cells, endothelial cells) was not altered. The CL-induced hypertrophy differed from that induced by chronic stimulation by endogenous norepinephrine (as in cold-adaptation) in absence of hyperplasia (there was a slightly reduced DNA content), absence of an increase in the thyroxine (T4) 5'-deiodinase activity, and absence of a selective increase in UCP concentration. WAT depots weighed less and had fewer cells (lower DNA content) in the CL-treated rats. Some multilocular adipocytes appeared in these normally almost exclusively unilocular WAT depots (mesenteric, inguinal, epididymal, retroperitoneal). We conclude that CL not only promotes BAT mitochondrial proliferation and thermogenesis and overall energy expenditure and leanness, but also retards the development of WAT hyperplasia during the early stage of diet-induced obesity.
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PMID:Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. 791 Apr 36

The level of sympathetic nervous system (SNS) activity in obesity is controversial, with reports claiming either increased or decreased SNS activity. The following studies examined SNS activity in a dietary form of obesity, ingestion of a lard-enriched diet for 4 wk. Plasma norepinephrine (NE) levels were 61% higher in rats fed the lard-enriched diet than in chow-fed controls at 20 degrees C (200 +/- 24 pg/ml vs. 124 +/- 6, P < 0.005) and remained elevated after 1 h of cold exposure (4 degrees C). [3H]NE turnover was markedly increased in heart, but not in interscapular brown adipose tissue (IBAT), kidney, liver, skeletal muscle, or spleen of rats fed the high-fat diet. By contrast, ingestion of a diet similarly enriched with sucrose raised rates of [3H]NE turnover in IBAT as well as in heart. Thus chronic ingestion of a lard-enriched diet induces region-specific stimulation of SNS activity that is greater in heart than in IBAT. Whereas the absence of an SNS response to lard in IBAT may contribute to weight gain in these animals, activation of cardiac sympathetic nerves may promote development of hypertension in this model of obesity.
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PMID:Effects of chronic lard feeding on sympathetic nervous system activity in the rat. 797 60

The influence of age on reflex cardiovascular responses, elicited by orthostatic change and Valsalva's maneuver was studied in 105 healthy volunteers, and the response to cold pressor test in 87 healthy adults. The age range of the subjects was 12 to 79 years old; they were stratified by decades for statistical analysis. Included in this study were only subjects without diseases, as evidenced by anamnesis, physical examination, blood pressure recording, ECG tracings, chest X-Ray and routine laboratory tests. None of subjects showed obesity, the body mass index was between 19.6 +/- 0.9 Kg/m2 in the 10-19 year old group and 25.2 +/- 1.2 Kg/m2 in the 50-59 year old group (mean +/- SE). Systolic and diastolic blood pressure (SBP, DBP) were between 113.6 +/- 4.2 and 64.2 +/- 2.9 mmHg respectively in the 10-19 years old group and 139.8 +/- 5.0 mmHg and 79.5 +/- 3.2 mmHg respectively in the 70-79 years old group (mean +/- SE). Heart rate in supine position varied between 71.2 +/- 3.2 beats/min in the 10-19 years group and 75.8 +/- 3.0 beats/min in the 70-79 years old group (mean +/- SE). Orthostatic response. Change from supine to standing position increased mean arterial pressure (MAP) by 10.0 +/- 1.25 mmHg in the 10-19 years old group; a similar increase occurred up to 40-49 years old group; from that age on, the response became bimodal, the percentage of subjects showing a MAP decrease upon standing, increased from 20% in the 50-59 years old group to 48% in the 70-79 years old group; MAP descents ranged between -5.3 +/- 0.63 and -12.6 +/- 1.37 mmHg (mean +/- SE) and were non symptomatic. The same bimodal pattern of responses was observed in the heart rate. Cold pressor test. In the 10-19 years old group the cold pressor test induced an increase of SBP and DBP of 17.6 +/- 5.0 mmHg and 11.5 +/- 3.5 mmHg (mean +/- SE) respectively, this response remained unchanged up to 40-49 years old age. After 50-59 years old this SBP and DBP increase was reduced by 50% and 63% in the 60-69 and 70-79 years old groups respectively. Return of SBP and DBP to cold prestimulation levels was normal in all studied groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Changes produced by age in cardiovascular reflex responses]. 800 37

Glucose turnover rate, 2-deoxy-D-[3H]glucose (2-DG) uptake, lipid synthesis in liver, white adipose tissue, and brown adipose tissue (BAT) were measured in lean FA/FA and genetically obese fa/fa rats either kept at 21 degrees C or acclimated to a cold environment (4 degrees C). After 10 days at 4 degrees C, lean rats increased their glucose turnover rate; 2-DG uptake as well as lipid synthesis in BAT were markedly stimulated. After cold acclimation, obese rats also increased glucose turnover; however, BAT glucose utilization was only slightly stimulated. Basal hyperinsulinemia and muscle insulin resistance of the obese group (as assessed by reduced 2-DG uptake in the soleus muscle) were present at room temperature and persisted at 4 degrees C. Total BAT lipid synthesis was increased to the same extent as in lean rats. Obese rat liver lipid synthesis, already much higher than normal at 21 degrees C, was further increased by cold exposure. We conclude that obese cold-acclimated fa/fa rats do not improve their muscle insulin resistance and barely improve BAT glucose utilization. We further suggest that an additional activation of hepatic lipid synthesis and oxidation thereof could participate in the heat production needed by the cold-acclimated obese rats.
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PMID:Modifications of glucose and lipid metabolism in cold-acclimated lean and genetically obese rats. 800 51

To study the first stages of excess fat deposition in Zucker rats, we artificially fed littermates with identical amounts of milk from 4 to 15-16 days of age while continuously recording oxygen consumption (VO2) and deep body temperature. Under intermittent cold loads simulating the periodic thermoregulatory stimulation experienced in the nest, differences between the amounts of body fat deposited by artificially reared fatty (fa/fa) and lean (Fa/-) pups were as large as those seen in mother-reared pups. The decreased VO2 of the cold-reared fatty pups could account for 90-100% of their extra fat deposition. At thermoneutrality, 16-day-old littermates reared with low feeding rates showed small but significant genotype differences in body fat that were not energetically accounted for by differences in VO2 or lean body mass. Slightly but significantly lower fecal energy losses indicated that differences in resorption might account for the positive energy balance of thermoneutrally reared fa/fa pups. Reduced energy expenditure thus efficiently fuels excess fat deposition but is not essential for the onset of excess fat deposition in fa/fa pups. Other factors than reduced sympathetic activation of brown adipose tissue must be considered as a primary cause for the development of fa/fa obesity.
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PMID:Onset of excess fat deposition in Zucker rats with and without decreased thermogenesis. 821 55

Weight loss reduces many of the health hazards associated with obesity including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, sleep apnea, hypoxemia and hypercarbia, and osteoarthritis. Potential adverse effects of weight loss include a greater risk for gallstone formation and cholecystitis, excessive loss of lean body mass, water and electrolyte problems, mild liver dysfunction, and elevated uric acid levels. Less consequential problems such as diarrhea, constipation, hair loss, and cold intolerance may also occur. The short-term adverse effects are not severe enough to contraindicate weight loss, nor do they outweigh its short-term benefits.
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PMID:Short-term medical benefits and adverse effects of weight loss. 836 5

The presence of nerve growth factor (NGF) and the ability of adrenergic stimulation to affect the rate of its synthesis in mouse, rat, and human brown adipose tissue (BAT) were investigated. Addition of conditioned medium, obtained from preconfluent and confluent brown adipocytes, to PC12 cells induced typical morphological changes similar to those due to NGF itself. Anti-NGF antibodies blocked this action. Moreover, NGF mRNA was detected by RT-PCR both in BAT and in brown adipocyte preparations. That NGF is synthesized in and released from brown fat cells was confirmed by immunoblotting. When the animals were exposed to low temperatures, NGF production declined. The effect of cold exposure could be mimicked by the addition of norepinephrine (NE) at day 4 or 8 (preconfluent and confluent cells, respectively). NE depletion obtained by reserpine injection induced a drastic increase of BAT NGF production. In both rat and human BAT, immunohistochemistry identified distinct anatomical structures that express the low affinity neurotropin receptor, termed p75NGFR. BAT production of NGF was higher in genetically obese rats and mice than in their lean counterparts, a difference that becomes more evident with age. Prolonged exposure to low temperature significantly decreased the BAT NGF synthesis also in obese animals. We conclude that NGF is synthesized in and released from brown fat cells, its production being inversely dependent on sympathetic activity, in both physiological and pathophysiological conditions, and increased in genetic animal models of obesity.
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PMID:Expression of nerve growth factor in brown adipose tissue: implications for thermogenesis and obesity. 859 94

Osteoarthritis (OA) is the most common rheumatologic disease, afflicting tens of millions of U.S. citizens. It is not an inevitable consequence of aging; rather, it is a degenerative process acquired because of metabolic, mechanical, genetic, and other influences. It is characterized by progressive loss of cartilage and bony overgrowth. Because cartilage is not innervated, the pain of OA arises from secondary effects, such as joint capsule distention, stretching of periosteal nerve endings, and, possibly, synovial inflammation. Psychologic factors, including stress and depression, may influence the perception of pain by OA patients. The risk of OA apparently is not increased by normal joint use, but persons who participate in competitive sports or who play with abnormal or injured joints are at increased risk. Obesity increases OA risk, and weight loss has been found to decrease it. Some forms of premature OA appear to be inherited. The objective diagnosis of OA is made on the basis of radiography. However, many individuals with radiographic evidence of OA are asymptomatic in the affected joint. It is essential to ensure that pain in the affected joint is attributable to OA and not another cause. The management of OA should include physical medicine measures such as heat or cold therapy and often neglected environmental measures, such as reducing chair height and using shoe orthotics. Therapeutic exercise is beneficial for many patients and includes an initial warm-up with range of motion, muscle strengthening, and aerobic activity (such as swimming). A major question in the pharmacologic management of OA is whether nonsteroidal anti-inflammatory drugs (NSAIDs) are superior to analgesics in terms of symptomatic relief; studies indicate that they are not. The question is relevant because of the adverse effects of NSAID use, particularly in the elderly population.
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PMID:New perspectives on osteoarthritis. 860 21

Organ transplantation has become a viable treatment for an increasing number of patients suffering from irreversible organ failure. In response to the steeply rising demand for transplantation, both the number of transplant centers and the number of patients on waiting lists have grown rapidly. Because organ donation has not kept pace with demand, each year a greater number of patients die while awaiting donor organs. (About 9% of all patients on the list in 1993 but not transplanted died. Death rates were highest, 19% and 16% respectively, for patients awaiting hearts and livers.) Among the factors contributing to the organ shortage are cultural and psychological barriers to donation and missed opportunities to request donation. An accompanying diminution in traumatic deaths of potential young donors has made older and other marginal, or higher-risk, donors the focus of studies on expansion of the donor pool. The studies reviewed herein evaluated donor risk factors such as age, disease (including infection), obesity, cold ischemia time, suboptimal organ function, and nontraumatic causes of death. Overall, broadened criteria for acceptable donor kidneys, hearts, and livers appear to lessen graft survival rates somewhat compared with rates for ideal donor organs. Nonetheless, use of higher-risk organs allows lifesaving transplants that could not otherwise be performed and results in acceptable prognoses for survival. Further research is needed to identify better tests for evaluating donor organs, provide longer-term follow-up of recipients of higher-risk organs, and develop alternative means to fill the donor-organ shortfall.
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PMID:Expanding the donor pool: use of marginal donors for solid organ transplantation. 865 91

In female mammals, reproduction is extremely sensitive to the availability of oxidizable metabolic fuels. When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise or fattening, reproductive attempts are suspended in favor of processes necessary for individual survival. Both reproductive physiology and sexual behaviors are influenced by food availability. Nutritional effects on reproductive physiology are mediated by changes in the activity of gonadotropin-releasing hormone (GnRH) neurons in the forebrain, whereas the suppression of sexual behaviors appears to be due, at least in part, to decreases in estrogen receptor in the ventromedial hypothalamus. Work using pharmacological inhibitors of glucose and fatty acid oxidation indicates that reproductive physiology and behavior respond to short-term (minute-to-minute or hour-to-hour) changes in metabolic fuel oxidation, rather than to any aspect of body size or composition (e.g., body fat content or fat-to-lean ratio). These metabolic cues seem to be detected in the viscera (most likely in the liver) and in the caudal hindbrain (probably in the area postrema). This metabolic information is then transmitted to the GnRH-secreting or estradiol-binding effector neurons in the forebrain. There is no evidence to date for direct detection of metabolic cues by these forebrain effector neurons. This metabolic fuels hypothesis is consistent with a large body of evidence and seems to account for the infertility that is seen in a number of situations, including famine, eating disorders, excessive exercise, cold exposure, lactation, some types of obesity, and poorly controlled diabetes mellitus.
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PMID:Control of fertility by metabolic cues. 925 2


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