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)

Adipose tissue and muscle lipoprotein lipase and postheparin hepatic and lipoprotein lipase activities have been measured in a group of 21 Pima Indian males over a wide range of body weight to determine the relationship between obesity and these lipase activities. There was a significant positive correlation between adipose tissue lipoprotein lipase and obesity; muscle and postheparin lipoprotein lipase and hepatic lipase were not related to degree of obesity. Fasting insulin levels were not related to any of the measurements of lipase activity. There were racial differences in adipose and postheparin lipoprotein lipase activities; both were significantly lower in the Pimas as compared with a group of weight-matched Caucasian males. Lipase activities were remeasured in eight subjects after a period of weight reduction including several weeks of stabilization at the reduced weights. After the period of weight reduction adipose tissue lipoprotein lipase declined in all subjects. Hepatic lipase also declined in all but two patients. Muscle and postheparin lipolytic activities were not affected by weight loss. The data indicate that (a) there are racial differences in adipose tissue lipoprotein lipase; and (b) the elevated adipose lipoprotein lipase associated with obesity, like many other biochemical variables in the obese state, returns toward normal after weight reduction.
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PMID:Characterization of lipase activities in obese Pima indians. Decreases with weight reduction. 711 15

A girl presented with small stature, obesity, tapetoretinal degeneration, deafness, psychomotor regression, seizures, acanthosis nigricans, hepatomegaly, and chronic tubulointerstitial nephropathy. She died at age ten with renal insufficiency and uncontrolled seizures. Histochemistry showed lipid storage in hepatocytes, histiocytes, smooth muscles and, to a much lesser extent, kidney tubules and cortical neurons. The liver had increased cholesterol esters (5-fold) and triacylglycerols (8-fold), and decreased phospholipids (50%). Methyllumbelliferyl-oleate, oleylcholestrol, trioleylglycerol, and tripalmitylglycerol lipase activities were markedly reduced in the liver, in the range found in Wolman's disease. In cirrhotic fatty livers these activities ranged from 7-87% of the normal mean. The patient's brain had limited neutral lipid storage and normal methyllumbelliferyl-oleate lipase. Trioleylglycerol lipase activity was 14-60% of controls; tripalmitylglycerol lipase activity 14-25% of controls; and oleylcholestrol lipase activity 12-33% of controls.
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PMID:Neutral lipid storage with acid lipase deficiency: a new variant of Wolman's disease with features of the Senior syndrome. 715 65

The activity of the post-heparin-lipase as well as of the cholesterol and triglyceride levels of test persons with normal weight and obese test persons of different age groups was established: 1. In normal persons (males and females) in mature age (30-45 years) a decrease of the enzyme activity takes place which is connected with an increase of the triglyceride content. Above all in older females a repeated increase of the post-heparin-lipase activity was observed, which positively correlates with the triglyceride level. While the decreases of the enzyme activity in mature age may be connected with processes of ageing, a repeated increase of the enzyme activity in older persons is perhaps induced by the increase of the triglyceride level. 2. Obese persons show higher enzyme activities in all age groups examined. Also in obese persons in mature age a decrease of the activity of post-heparin-lipase is to be established. The ageing development of the enzyme activity of the post-heparin-lipase is similar to that of normal persons, takes place, however, at a higher level. 3. The cholesterol and triglyceride levels of the obese persons examined were on an average higher than those of normal persons of the same age group. A dependence of age of these parameters was not observed in the adipose patients.
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PMID:[Lipoprotein lipase activity in healthy subjects and patients with metabolic disorders]. 728 30

The existence of a DNA polymorphism at the hormone-sensitive lipase locus could be of great interest for genetic analysis of obesity and related disorders since hormone-sensitive lipase is the rate-limiting enzyme of adipose tissue lipolysis and therefore plays a key role in energy metabolism. The polymorphic dinucleotide repeat D19S120 was identified within a human genomic clone selected with a rat hormone-sensitive lipase cDNA. This marker was subsequently localized to the short arm of chromosome 19 (p13.3) whereas human hormone-sensitive lipase (LIPE) had been mapped to the long arm of chromosome 19 (q13.1-->13.2). A duplication of the hormone-sensitive lipase gene or the presence of a pseudogene could explain the discrepancy. Cosmids from the two regions were analyzed in Southern blot experiments. A human adipose tissue hormone-sensitive lipase full-length cDNA probe hybridized only to cosmids from the 19q13.1-->13.2 region whereas the D19S120 amplicon probe hybridized only to cosmids from the p13.3 region. These data show that the occurrence of gene duplication or the presence of a pseudogene on the short arm of chromosome 19 is very unlikely and that D19S120 is unrelated to the hormone-sensitive lipase gene.
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PMID:The hormone-sensitive lipase (LIPE) gene located on chromosome 19q13.1-->13.2 is not duplicated on 19p13.3. 748 32

It is still uncertain whether subgroups of obese subjects demonstrate different eating patterns. The aim of this report is to compare data on dietary intake obtained by different methods (dietary history and dietary diary) in several groups of obese patients in which the effects of weight-reducing agents were investigated. In our first and our second study, the latter part of an international multicenter study, we investigated the weight-reducing potential of lipase inhibition, a novel concept in the treatment of obesity, in healthy moderately obese subjects. In the third study, part of a national multicenter study, we investigated the effect of a serotoninergic drug (dexfenfluramine) on eating habits in moderately obese people who considered themselves snackers. Eating habits of the third group seem to be different from those of the other two groups in both men and women. These patients have a greater total energy intake due to a greater carbohydrate and fat intake. In our second study, little difference is found when results obtained by dietary history are compared with those obtained by dietary diaries. Our comparisons indicate that groups of obese patients with different patterns of eating behavior may exist and that obese snackers have a significantly greater energy intake. Therefore, various therapeutic strategies for weight reduction may be useful for patients with different types of eating behaviors. Furthermore, the methods by which data on dietary intake are obtained seem to show comparable results and therefore at least suggest accuracy.
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PMID:Eating habits of obese patients in The Netherlands: a comparison between various subgroups and the general Dutch population. 786 38

Bearing in mind the importance of upper-body obesity for the insulin resistance (or metabolic) syndrome and the abnormalities in free fatty acid metabolism associated with this disorder, the regulation of lipolysis in isolated subcutaneous adipocytes was investigated in 13 72-yr old upper-body obese men with insulin resistance and glucose intolerance and in 10 healthy 72-yr-old men. There was a marked resistance to the lipolytic effect of noradrenaline in the metabolic syndrome due to defects at two different levels in the lipolytic cascade. First, an 80-fold decrease in sensitivity to the beta 2-selective agonist terbutaline (P < 0.001) which could be ascribed to a 50% reduced number of beta 2-receptors (P < 0.005) as determined with radioligand binding. The groups did not differ as regards dobutamine (beta 1) or clonidine (alpha-2) sensitivity, nor beta 1-receptor number. The mRNA levels for beta 1- and beta 2-receptors were similar in the two groups. Second, the maximum stimulated lipolytic rate was markedly reduced in the metabolic syndrome. This was true for isoprenaline (nonselective beta-agonist), forskolin (activating adenylyl cyclase), and dibutyryl cAMP (activating protein kinase). In regression analysis, the observed abnormalities in lipolysis regulation correlated in an independent way with the degree of glucose intolerance (r = -0.67) and beta 2-receptor number with insulin resistance (r = 0.67). In conclusion, the results of this study indicate the existence of lipolytic resistance to catecholamines in the adipose tissue of elderly men with the metabolic syndrome, which may be of importance for impaired insulin action and glucose intolerance. The resistance is located at a posttranscriptional level of beta 2-receptor expression and at the protein kinase-hormone sensitive lipase level.
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PMID:Multiple lipolysis defects in the insulin resistance (metabolic) syndrome. 820 Sep 97

Hydrolysis of triglycerides to fatty acids and glycerol in fat cells (lipolysis) is of importance for the control of lipid and carbohydrate metabolism. This process is regulated by several hormones and parahormones acting on cyclic AMP formation or breakdown, which in turn influences the activity of hormone sensitive lipase. The latter enzyme stimulates hydrolysis of triglycerides in fat cells. It is well established through in vivo and in vitro investigations that there are regional variations in the lipolytic activity of human adipose tissue. The rate of lipolysis is low in the subcutaneous femoral/gluteal region, intermediate in the subcutaneous abdominal region and high in the visceral (i.e. omental) region. In non-obese subjects the differences between the subcutaneous and visceral fat depots may be explained by site variations in the function of receptors for insulin, catecholamines and adenosine. The lipolytic beta 1 and beta 2 adrenoceptors, as well as the newly discovered beta 3, are most active in the visceral fat cells. The antilipolytic insulin receptors, alpha 2 adrenoceptors and adenosine receptors are most active in the subcutaneous fat cells. In subjects with upper-body obesity the regional variations in the action of catecholamines on lipolysis are further enhanced. Decreased action of beta 2-adrenergic receptors and increased activity of alpha 2-adrenergic adrenoceptors in combination with defects in hormone sensitive lipase function inhibits the lipolytic effect of catecholamines in subcutaneous fat cells whereas increased activity of beta 3-adrenergic receptors and decreased activity of alpha 2 adrenoceptors augment the lipolytic response in visceral fat cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differences in lipolysis between human subcutaneous and omental adipose tissues. 851 4

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
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PMID:Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. 865 34

Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.
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PMID:Combined drug treatment of obesity. 869 49

Lipase inhibition, leading to decreased intestinal fat adsorption can be used in the treatment of obesity. Orlistat, a lipase inhibitor, in a dose of 50 mg three times a day leads to a significant increase in weight loss compared to placebo in moderately obese people. These results are confirmed in a multiple-dose study using 10 mg, 60 mg and 120 mg Orlistat three times a day vs. placebo. The use of lipase inhibition has no significant influence on fasting levels of several hormonal systems, including thyroid hormones, catecholamines and IGF-I. The same is true for the responses of several gastrointestinal and pancreatic hormones after a liquid high-fat mixed meal. In general, Orlistat is tolerated very well, although a higher occurrence of gastrointestinal side effects is seen.
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PMID:First clinical studies with orlistat: a short review. 869 67


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