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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new automated potentiometric method for the determination of colipase was developed, taking advantage of the reactivation of purified lipase, in the presence of bile salt and at pH 6.5. High-fat and high-starch diets induced an opposite regulation of lipase and amylase in the rat pancreas. At the same time, the level of colipase was not influenced by nutrition. During fasting and in alloxan diabetes, the specific activity of lipase almost doubled, that of amylase decreased sharply, and colipase was not affected in the rat pancreas. In obese-hyperglycemic mice, suffering from obesity, hyperinsulinism, and moderate diabetes, there was also no regulation of pancreatic colipase. Thus, at variance with a number of hydrolases, there was no dietary or hormonal adaptation of colipase. However, this was probably without any bearing on intraluminal lipolysis. Indeed, comparison of lipase and colipase activities in pancreas and in small intestine suggests that colipase concentration is not a limiting factor of intraluminal lipolysis. The molecular mechanism of this assumption is discussed on the basis of in vitro studies.
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PMID:Lack of adaptation of pancreatic colipase in rats and mice. 84 20

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

The effects of adrenalectomy on the feeding response to enterostatin and the mRNA levels of its parent protein, pancreatic colipase, have been investigated in lean (fa/?) and genetically obese (fa/fa) rats. Adrenalectomy reduced body weight gain and food intake of obese rats. Enterostatin inhibited the intake of high-fat diet in obese rats but not in lean rats. Adrenalectomy reduced food intake of all rats and abolished the response to enterostatin in the obese group. Obese rats had low levels of colipase mRNA, but these were normalized after adrenalectomy. The ability to respond to exogenous enterostatin is possibly linked to low levels of production of the peptide. The effects of adrenalectomy on brown adipose tissue uncoupling protein (UCP) mRNA and beta 3-adrenergic receptor (beta 3-AR) mRNA were also investigated. Northern blot analysis showed low levels of both UCP mRNA and beta 3-AR mRNA in obese rats that were restored to or toward the normal levels of lean rats by adrenalectomy. Adrenalectomy had no significant effects on mRNA levels in lean rats.
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PMID:Adrenalectomy of the obese Zucker rat: effects on the feeding response to enterostatin and specific mRNA levels. 839 27

A high fat intake, together with an inability to match lipid oxidation to fat intake, has been found to be correlated with obesity in humans. This review describes our current understanding of enterostatin, a peptide that selectively reduces fat intake. Enterostatin is formed in the intestine by the cleavage of secreted pancreatic procolipase, the remaining colipase serving as an obligatory cofactor for pancreatic lipase during fat digestion. Enterostatin is also produced in the gastric mucosa and the mucosal epithelia of the small intestine. Procolipase gene transcription and enterostatin release into the gastrointestinal lumen are increased by high-fat diets. After feeding, enterostatin appears in the lymph and circulation. Enterostatin will selectively inhibit fat intake during normal feeding and in experimental paradigms that involve dietary choice. Its anorectic effect has been demonstrated in a number of species. Both peripheral and central sites of action have been proposed. The peripheral mechanism involves an afferent vagal signaling pathway to hypothalamic centers. The central responses are mediated through a pathway that includes both serotonergic and opioidergic components. Chronically, enterostatin reduces fat intake, bodyweight, and body fat. This response may involve multiple metabolic effects of enterostatin, which include a reduction of insulin secretion, an increase in sympathetic drive to brown adipose tissue, and the stimulation of adrenal corticosteroid secretion. A possible pathophysiological role is suggested by studies that have linked low enterostatin production and/or responsiveness to strains of rat that become obese and prefer dietary fat. Humans with obesity also exhibit a lower secretion of pancreatic procolipase after a test meal, compared with persons of normal weight.
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PMID:Enterostatin--a peptide regulating fat intake. 928 45

Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of procolipase after tryptic cleavage and belong to the family of gut-brain peptides. Although enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined. To determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR and APGPR levels were measured in 38 overnight-fasted subjects (body mass index, 17.9-54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of lean subjects was significantly lower than that in obese subjects [lean = 603 +/- 86 nmol/L (n = 17); obese, 1516 +/- 227 nmol/L (n = 21); P = 0.0023]. In addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was significantly higher in lean than in obese subjects [lean, 1.71 +/- 0.24 (n = 17); obese, 1.05 +/- 0.14 (n = 21); P = 0.0332]. The results of these studies show hyperenterostatinemia in obesity and a diminution in enterostatin secretion after satiety.
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PMID:Hyperenterostatinemia in premenopausal obese women. 1008 74

Food intake is a regulated system. Afferent signals provide information to the central nervous system, which is the centre for the control of satiety or food seeking. Such signals can begin even before food is ingested through visual, auditory and olfactory stimuli. One of the recent interesting findings is the demonstration that there are selective fatty acid taste receptors on the tongue of rodents. The suppression of food intake by essential fatty acids infused into the stomach and the suppression of electrical signals in taste buds reflect activation of a K rectifier channel (K 1.5). In animals that become fat eating a high-fat diet the suppression of this current by linoleic acid is less than that in animals that are resistant to obesity induced by dietary fat. Inhibition of fatty acid oxidation with either mercaptoacetate (which blocks acetyl-CoA dehydrogenase) or methylpalmoxirate will increase food intake. When animals have a choice of food, mercaptoacetate stimulates the intake of protein and carbohydrate, but not fat. Afferent gut signals also signal satiety. The first of these gut signals to be identified was cholecystokinin (CCK). When CCK acts on CCK-A receptors in the gastrointestinal tract, food intake is suppressed. These signals are transmitted by the vagus nerve to the nucleus tractus solitarius and thence to higher centres including the lateral parabrachial nucleus, amygdala, and other sites. Rats that lack the CCK-A receptor become obese, but transgenic mice lacking CCK-A receptors do not become obese. CCK inhibits food intake in human subjects. Enterostatin, the pentapeptide produced when pancreatic colipase is cleaved in the gut, has been shown to reduce food intake. This peptide differs in its action from CCK by selectively reducing fat intake. Enterostatin reduces hunger ratings in human subjects. Bombesin and its human analogue, gastrin inhibitory peptide (also gastrin-insulin peptide), reduce food intake in obese and lean subjects. Animals lacking bombesin-3 receptor become obese, suggesting that this peptide may also be important. Circulating glucose concentrations show a dip before the onset of most meals in human subjects and rodents. When the glucose dip is prevented, the next meal is delayed. The dip in glucose is preceded by a rise in insulin, and stimulating insulin release will decrease circulating glucose and lead to food intake. Pyruvate and lactate inhibit food intake differently in animals that become obese compared with lean animals. Leptin released from fat cells is an important peripheral signal from fat stores which modulates food intake. Leptin deficiency or leptin receptor defects produce massive obesity. This peptide signals a variety of central mechanisms by acting on receptors in the arcuate nucleus and hypothalamus. Pancreatic hormones including glucagon, amylin and pancreatic polypeptide reduce food intake. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte-stimulating hormone, growth hormone and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides that modulate feeding. beta-Casomorphin, a heptapeptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group, including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines and thyrotropin-releasing hormone, all decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors that relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.
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PMID:Afferent signals regulating food intake. 1099 53

High-fat diets are often associated with greater caloric intake and weight gain. Since satiety during fat intake is induced by fat in the intestine we investigated the efficiency of a lipid compound that retards fat digestion to regulate fat intake. We found this compound to reduce high-fat food intake, body weight and blood lipids in Sprague-Dawley rats, without causing steatorrhea. The absence of steatorrhea is explained by an increased pancreatic lipase/colipase secretion, compensating the impaired lipolysis by the added compound. The animals also had an elevated CCK secretion. The satiety for fat may be the consequence of elevated CCK and procolipase/enterostatin levels. We conclude that compounds can be found that delay intestinal fat digestion and control high-fat food intake through the release of satiety signals, without causing steatorrhea. The absence of steatorrhea makes such compounds advantageous over lipase inhibitors in the treatment of obesity.
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PMID:Appetite suppression through delayed fat digestion. 1695 81

It is widely known that the interfacial quality of lipid emulsion droplets influences the rate and extent of lipolysis. The aim of this work was to investigate the effect of two galactolipids, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), adsorbed at the interface on in vitro digestibility of olive oil by porcine pancreatic lipase. The experiments were performed under simulated duodenal conditions in the presence of phosphatidylcholine (lecithin) and bile salts. It was found that emulsions prepared with DGDG had a longer lag phase prior to lipase activation with a decrease in lipolysis rate. In contrast, no inhibitory effect on lipase kinetics was observed in emulsions prepared with MGDG. We postulated that the larger headgroup and more tightly packed molecular organization of DGDG at the interface gave rise to steric hindrance that retarded colipase and lipase adsorption onto the substrate surfaces and hence delayed and reduced lipolysis. It was noted that the lag phase and lipolysis rate strongly depended on the DGDG/lecithin molar ratio in the systems: the higher the molar ratio, the longer the lag phase followed by a reduced lipolysis rate. The ability of DGDG to inhibit bile salt adsorption/displacement was also investigated. The results showed that bile salts did not completely displace DGDG from the interface, explaining the reason why DGDG still possessed inhibitory activity even in the presence of bile salts at a physiological relevant concentration. The results provide interesting insights into the influence of the galactolipid headgroup and lecithin on the emulsion interfacial quality which in turn regulates the lipolysis. The findings potentially could lead to the production of generic foods and drugs designed for regulating dietary fat absorption in the prevention and treatment of obesity and related disorders.
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PMID:Modulating pancreatic lipase activity with galactolipids: effects of emulsion interfacial composition. 1943 74

A pentapeptide released from procolipase, enterostatin, selectively attenuates dietary fat intake when administered peripherally or centrally. Enterostatin may act through the afferent vagus nerve and in the hypothalamus and amygdala, primarily in the central nucleus of the amygdala. To investigate the physiological role of endogenous enterostatin, we created an enterostatin-deficient, colipase-sufficient (Ent(-/-)) mouse. Ent(-/-) mice are viable, normally active, and fertile. They exhibit normal growth on low-fat and high-fat diets. Furthermore, Ent(-/-) mice develop diet-induced obesity, as do Ent(+/+) mice, and have normal responses to a two-macronutrient choice diet and to a switch from a high-fat to a low-fat diet. Levels of total serum (P = 0.004) and non-HDL (P <or= 0.001) cholesterol were higher and levels of HDL cholesterol (P = 0.01) were lower in Ent(-/-) than in wild-type mice. To determine whether enterostatin contributed to the decreased survival or whether colipase deficiency was the sole contributor, we administered enterostatin to procolipase-deficient (Clps(-/-)) mouse pups. Enterostatin significantly improved survival (P <or= 0.001). Our results demonstrate that enterostatin is not critically required to regulate food intake or growth, suggesting that other pathways may compensate for the loss of enterostatin. Enterostatin has developmental effects on survival of newborns and alters cholesterol metabolism.
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PMID:Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in mice. 1962 81

The most widely used pharmacological therapies for obesity and weight management are based on inhibition of gastrointestinal lipases, resulting in a reduced energy yield of ingested foods by reducing dietary lipid absorption. Colipase-dependent pancreatic lipase is believed to be the major gastrointestinal enzyme involved in catalysis of lipid ester bonds. There is scant literature on the action of pancreatic lipase under the range of physiological conditions that occur within the human small intestine, and the literature that does exist is often contradictory. Due to the importance of pancreatic lipase activity to nutrition and weight management, the present review aims to assess the current body of knowledge with regards to the physiology behind the action of this unique gastrointestinal enzyme system. Existing data would suggest that pancreatic lipase activity is affected by intestinal pH, the presence of colipase and bile salts, but not by the physiological range of Ca ion concentration (as is commonly assumed). The control of secretion of pancreatic lipase and its associated factors appears to be driven by gastrointestinal luminal content, particularly the presence of acid or digested proteins and fats in the duodenal lumen. Secretion of colipase, bile acids and pancreatic lipase is driven by cholecystokinin and secretin release.
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PMID:Physiological parameters governing the action of pancreatic lipase. 2019 96


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