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)

Tetrahydrolipstatin (THL) is a selective inhibitor of fat absorption. In animal models, it has anti-obesity and anti-hypercholesterolemic activity and is presently in clinical trials for these indications. THL binds covalently to pancreatic lipase. Complete inhibition of lipolytic activity is obtained concomitant with the incorporation of 1 mol of THL/mol of enzyme. Pancreatic lipase is the best studied lipase, but published results concerning its catalytic mechanism are still controversial. In order to learn more about the inhibitory mechanism of THL, a selective lipase inhibitor interacting at or near the catalytic site, and therefore, to obtain more information on the catalytic mechanism of lipase, we have determined the amino acid residue to which THL is bound. After proteolytic degradation of porcine pancreatic lipase inhibited with radioactively labeled THL, the labeled peptides were isolated and analyzed by quantitative amino acid analysis, N-terminal sequencing, and by mass spectrometry with fast atom bombardment ionization. The data clearly show that THL is bound as an ester to the serine 152 of the lipase.
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PMID:The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase. 189 34

We studied the lipase and colipase activity in pancreatic acinar tissue of insulin-deficiency and insulin-resistance obese Zucker rats (fa/fa). After injection of streptozotocin (STX 75 mg/kg) in normal Sprague-Dawley rats, the activity of lipase and colipase in pancreatic acinar tissue was increased by approximately 100%, the increase in colipase occurring 3 days later than that of lipase. At the same time, the amylase activity was decreased by 98%. Injection of alloxan (125 mg/kg) induced a similar change of pancreatic enzyme pattern, with amylase activity strongly reduced by 79% and activity of lipase and colipase increased 20.5 and 18.6%, respectively. Correction of the diabetic state with insulin (1 U/100 g/day) reversed the activity of these enzymes to their prediabetic levels. Administration of insulin (6 U/100 g/day) to normal Sprague-Dawley rats increased the activity of amylase as well as lipase and colipase, whereas injection of glucagon (0.3 mg/100 g/day) decreased the activity of amylase and colipase but had no significant effect on lipase activity. In the obese Zucker rats (fa/fa), the activity of lipase and colipase at onset of obesity (5 weeks of age) was lower than that in their lean littermates (fa/o). Thereafter the activity of the two proteins increased with age, being 40% higher in the fa/fa rat than in the fa/o rat at age 7 weeks. During the same period, amylase activity decreased. These results indicate that pancreatic lipase and colipase activity are increased following either insulin deficiency or insulin resistance in rats by a mechanism related to the changed levels of insulin.
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PMID:Pancreatic lipase and colipase activity increase in pancreatic acinar tissue of diabetic rats. 247 69

We previously found that massively obese patients respond with less gastric acid secretion in response to vagal stimulation. This is compatible with the described association between experimental obesity and altered vagal function in the rat. To confirm this observation, the pancreatic and biliary responses to vagal stimulation were examined in nine nondiabetic obese patients against a background secretin infusion of 15 CU x h-1, and monitored after a subsequent injection of 75 IDU of cholecystokinin. Two separate marker perfusion systems were used in the stomach and duodenum, respectively, and blood samples were drawn for hormone analyses. In contrast to controls having normal body weight, the obese patients failed to respond with increments of pancreatic enzyme secretion and duodenal bile acids after stimulation with modified sham feeding. Cholecystokinin stimulated the pancreatic secretion of trypsin, amylase, and lipase, the emptying of bile acids, and the release of gastrin, but the patients' responses were only half that of the controls. In the resting state the obese had higher outputs of bile and pancreatic enzymes and higher plasma levels of pancreatic polypeptide compared with controls, but the pancreatic bicarbonate secretion rate was not different. The almost complete suppression of the basal gastric acid secretion by a low dose of intravenous (IV) secretin in controls did not occur in the obese. We conclude that massive obesity is associated with a reduced pancreatic and biliary response to vagal stimulation. Compared with controls, the digestive functions of the obese patients seem to be less sensitive to stimulation by exogenous cholecystokinin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired pancreatico-biliary response to vagal stimulation and to cholecystokinin in human obesity. 328 31

Fifteen grossly obese patients were studied before and 6-8 months after gastroplasty. Their mean body weight decreased by 30% (from 127 +/- 13 to 97 +/- 14 kg, mean +/- SD). The preoperative hyperinsulinemia, hyperglucosemia and hyperglucagonemia were significantly reduced at follow up. Liproprotein lipase activity, measured in post-heparin plasma, was slightly reduced and did not change after weight reduction. Variables reflecting thyroid function were within the reference ranges; small but statistically significant reductions in serum thyroxine and reverse triiodothyronine levels were recorded. Adipocyte heat production, reflecting total cellular metabolic activity and registered by microcalorimetry, was significantly decreased before surgery (by about 60 per cent when expressed per g tissue and by about 20 per cent when expressed per cell) and increased significantly at follow-up; expressed per cell, the heat production was normalized, but expressed per g tissue the values were still about 15 per cent before those of a control group. The results indicate that the reduced adipocyte heat production in obese individuals is a consequent rather than a cause of severe obesity.
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PMID:Adipocyte heat production before and after weight reduction by gastroplasty. 352 54

To investigate the reasons for the lack of sex differences in high density lipoproteins (HDL) observed in population studies of the Pima Indians, we selected 18 lean (9 men, 9 women, body mass index (BMI) less than 27) and 22 obese (12 men, 10 women, BMI greater than 27) Pima Indians for an inpatient study of HDL composition. We measured lipase activities and steroid hormone concentrations, both of which have previously been implicated in the control of HDL. The lean women had higher concentrations of HDL and HDL2 than did either the obese women or the lean or obese men. Lean women had significantly lower hepatic lipase activities and significantly higher concentrations of estradiol compared to obese women. Lean women also had different HDL2 composition, as indicated by the molar ratio of HDL2 cholesterol/A-I. Significant negative correlations between HDL and obesity measured by either BMI or percent body fat were observed in both sexes, but the slope of the relationship was steeper in women. Significant negative associations were observed between HDL or HDL2 concentrations and hepatic lipase in both sexes, and there were significant positive associations between HDL2 and plasma estradiol in women. The data suggest that obesity in this population has a stronger negative influence on HDL concentrations in women, possibly through changes in estradiol and hepatic lipase activities. Since there are so few lean women in the Pima population, the net result is that HDL levels in women in the population as a whole do not differ from those of men.
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PMID:Lack of sex differences in high density lipoproteins in Pima Indians. Studies of obesity, lipase activities, and steroid hormones. 359 76

A physiological in vivo increase of plasma free fatty acid concentration after an overnight fast was found to be accompanied by a rise of the non-protein bound estradiol fraction. A similar increase was observed after lipase activation by the i.v. injection of 500 IU heparin in 5 healthy non-fasting subjects. In vitro studies showed a direct relationship between non-protein bound estradiol and the concentration of linoleate, linolenate, and arachidonate both in undiluted serum and in Ringer's solution containing human serum albumin (45 g/liter). Moreover, the estradiol sex hormone binding globulin complex bound to a solid concanavalin A-Sepharose matrix was markedly dissociated by oleate and even more by linoleate, linolenate, or arachidonate. These results suggest that physiological diurnal elevations in plasma free fatty acids which are amplified by high fat consumption, obesity, and stress may imply major proportional increases of available estradiol, exerting a promotional effect on breast and endometrial cancer over the years.
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PMID:Free fatty acid concentrations correlated with the available fraction of estradiol in human plasma. 369

In vitro experiments using both primary fetal hepatocyle cultures and adipoblast cultures have demonstrated that the presence of the fa gene is associated with decreased synthetic capacity, when compared to wild-type cultures. These results are in contrast to the elevated lipogensis and lipoprotein-lipase activities found in vivo in young adult obses (fafa) Zucker rats compared to their lean littermates. These studies used adipoblast cultures to address three possible explanations for these in vitro-in vivo differences: 1) FaFa and fafa adipoblast cultures represent different cell populations with intrinsically different abilities to differentiate, ie, to lipid-fill. 2) The decreased synthetic capacities in fafa vs FaFa adipoblast cultures are specific to cultures derived from the epididymal pad. 3) Cultured adipoblasts produce factor(s) that affect adipoblast differentiation in vitro. Results indicate that 1) the rate of differentiation is slower in fafa than in FaFa adipoblasts 2) there are depot-related differences in lipid metabolism, but these differences do not negate the in vitro association between the fa gene and decreased synthetic capacity and 3) FaFa epididymal-derived adipoblasts produce a factor(s) that affects inguinal-derived adipoblast differentiation and/or growth in vitro. Thus it is important to take both the site of cell origin and culture conditions into consideration when using in vitro systems as an approach to understanding complex in vivo disorders, such as obesity in the Zucker fafa rat.
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PMID:Adipoblasts from the Zucker fafa rat. 384 Jul 74

The presence of a lipidbound inhibitor in adipose tissue of rats with hypothalamic obesity may explain the failure of the tissue to release fatty acids on epinephrine stinmulation. Aqueous extracts of tissue from obese animals showed no deficiency of lipase activity, but when whole homogenates of epididymal fat from lean and obese animals were mixed, 25 percent tissue from obese animals reduced by 73 percent the release expected from tissue of lean controls.
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PMID:Lipolysis in homogenates of adipose tissue: an inhibitor found in fat from obese rats. 600 38

Weanling male rats with ventromedial hypothalamic lesions (VMNL rats) and sham-operated controls were killed 1, 2, 4, and 5 weeks postoperatively. The VMNL rats developed normophagic hypothalamic obesity in the presence of normal body weight and reduced linear growth. In both VMNL and control rats, pancreatic weight and protein content increased with time but were lower in the lesioned animals. Pancreatic DNA content was arrested in VMNL rats and remained so during the remainder of the experiment. The only significant enzyme changes (trypsinogen, amylase, and lipase) were evident in higher trypsinogen concentration in VMNL rats during 2 and 4 weeks after lesion production. In view of previous data on both hypophysectomized and VMNL rats and the known role of the ventromedial hypothalamic nucleus in neuroendocrine and neuroautonomic function, it is speculated that the changes observed here are in part due to disruption of neuroendocrine and in part due to disturbance of neuroautonomic control systems.
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PMID:Pancreatic growth and enzyme profiles in weanling rats with normophagic hypothalamic obesity. 608 27

A total of 128 patients with alimentary obesity were examined in the course of the treatment. There was a significant elevation in blood serum of total and free cholesterol, its esters, free fatty acids, beta-lipoproteins, and a decrease in the activity of serum lipase. The correlation of cholesterol esters to phospholipids was found to be disordered. Eighty patients demonstrated, after treatment with chloride sodium bromoiodine baths combined with hypocaloric diet and exercise therapy, a favourable clinical time course and normalization of the majority of lipid metabolism indicators, with an increase in serum lipase activity. Twenty-five patients, who received fresh baths under similar conditions, demonstrated less pronounced shifts in lipid metabolism, which were not always significant. The treatment complex including phepranon also gave rise to the normalization of the majority of lipid metabolism indicators. However, one-third of cases developed serious side effects.
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PMID:[Dynamics of lipid metabolism in the combined treatment of alimentary obesity]. 651 36


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