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

Ketone body production and oxidation of 14C fatty acids to CO2 were measured in hepatocytes isolated from lean and obese Zucker rats. The oxidation of [1-14C]octanoate, [1-14C]palmitate and [1-14C]palmitoyl carnitine to 14CO2 was 50%--70% less in obese than in lean rats. Although ketone body production in hepatocytes from both lean and obese rats was increased by fasting, there was a significantly lower rate of ketone body production in hepatocytes from obese rats. Ketone body production was reduced to a comparable extent by increasing the glucose concentration in the incubation media of hepatocytes from both lean and obese rats. Glucagon and carnitine increased ketogenesis and the effect were additive and similar in lean and obese rats. These data suggest that beta-oxidation and ketogenesis are suppressed in the obese Zucker rat, and further that ketone bodies can be modulated similarly in hepatocytes from lean and obese rats by nutritional and hormonal intervention. It is postulated that the decreased beta-oxidation and ketone body production may play a role in the development or maintenance of obesity in the Zucker rat.
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PMID:Oxidation and ketogenesis in hepatocytes of lean and obese Zucker rats. 680 48

Glucagon secretion was studied in rats with electrolytic lesions of the bilateral ventromedial hypothalamic area (VMH-L) under various experimental conditions. The results obtained are as follows: 1. The basal plasma level of immunoreactive glucagon (IRG) was lowered in VMH-L rats 5 and 10 weeks after the operation. Plasma IRG levels after 24-hour starvation and during the arginine load were more significantly decreased in the VMH-L rats than in the control group. 2. The basal plasma level of immunoreactive insulin (IRI) showed significant positive correlations with body weight and Lee's index in these rats. The basal plasma level of IRG showed significant negative correlations with body weight, Lee's index and basal plasma IRI level. 3. In response to the arginine load, the plasma IRI level was significantly increased in VMH-L rats immediately after the operation, and the plasma IRG level was more significantly decreased in VMH-L rats 1 week after the operation than in the control group. 4. The response of plasma IRG to the arginine load was also lowered more in VMH-L rats than in rats pair-fed for 4 weeks after the operation. 5. 15 weeks after the operation, there was no significant difference in response of plasma IRI and IRG to the subcutaneous injection of epinephrine between VMH-L and control rats. These findings indicate that hypoglucagonemia in the VMH-L rats was induced by various factors, such as disorder of the autonomic nervous system, excessive insulin release, etc. The impairment of glucagon secretion may contribute to the development of obesity observed in rats with VMH-lesions.
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PMID:[Studies on glucagon secretion in obese rats with hypothalamic lesions (author's transl)]. 700 30

Responsiveness of glucagon secretion to various stimuli was examined in Zucker fatty rats. Epinephrine infusion and cold exposure increased the plasma glucagon level to the same extent in fatty and lean rats, although the plasma glucose responses to these stimuli were much higher in fatty rats than in lean rats. Glucagon secretion in response to hypoglycemia due to insulin administration was markedly blunted in fatty rats. When arginine was infused, fatty rats showed enhanced secretion of glucagon and insulin, and elevation of plasma glucose as compared with lean rats. Streptozotocin (STZ)-treatment of fatty rats decreased insulin response to arginine but had no effect on exaggerated glucagon secretion. Arginine-stimulated glucagon secretion of lean rats was exaggerated by STZ treatment. From these results, glucagon secretion of fatty rats seemed unresponsive to inhibitory effects of glucose and insulin. The ventromedial hypothalamus-lesioned obese rats showed enhanced secretion of glucagon and insulin, and elevation of plasma glucose in response to arginine as observed in fatty rats. We conclude that the abnormalities of A cells in fatty rats are presumably secondary to obesity rather than caused by the fa gene.
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PMID:Abnormal glucagon secretion in Zucker fatty rats. 726 23

In previous studies on the enteroinsular axis in Zucker rats, it was found that glucose-dependent insulinotropic polypeptide (GIP) levels were normal in obese animals, but the glucose threshold for the insulinotropic action of GIP in the perfused rat pancreas was reduced. Glucagon-like peptide I (GLP-I)(7-36) is also an important incretin, and in the current study, glucose, insulin, and immunoreactive (IR)-COOH-terminal GLP-I responses to oral glucose were compared in lean (Fa/?) and obese (fa/fa) rats. In addition, the concentration thresholds for stimulation and glucose dependence of perfused pancreases to GLP-I(7-36) were examined. Glucose responses to oral glucose were similar in fa/fa and Fa/? rats. Obese animals were hyperinsulinemic when fasting and after oral glucose. Significant increases in IR-GLP-I levels in response to glucose were only observed in fa/fa rats. Perfused pancreases from fa/fa rats hypersecreted insulin at all glucose concentrations. In the presence of 4.4 mmol/l glucose, GLP-I(7-36) increased insulin secretion in fa/fa pancreases approximately 25-fold, whereas there was only a 5-fold increase in Fa/? pancreases. Pancreases from fa/fa rats, perfused with a glucose gradient (2.8-11 mmol/l) in the presence of GLP-I(7-36), responded with an immediate increase in insulin secretion, i.e., at a glucose concentration of 2.8 mmol/l, whereas Fa/? pancreases required a minimum of 4.22 mmol/l glucose for stimulation. With high glucose (16.7 mmol/l), both fa/fa and Fa/? rat pancreases exhibited similar responsiveness to GLP-I(7-36), having thresholds of < 50 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered glucose dependence of glucagon-like peptide I(7-36)-induced insulin secretion from the Zucker (fa/fa) rat pancreas. 772 5

Pancreatic glucagon, in addition to its metabolic effects, appears to accelerate postprandial satiety which controls meal size. Glucagon is released during meals. Administration of glucagon at the beginning of meals reduces the size of test meals in animals and humans, and reduces the size of spontaneous meals in rats. This effect is behaviorally indistinguishable from normal satiety in rats and subjectively indistinguishable from normal satiety in humans. Antagonism of the action of endogenous glucagon during meals by administration of glucagon antibodies increases both test meals and spontaneous meals. These results indicate that glucagon is a physiological satiety signal. The possible mechanisms through which glucagon's effect is transduced into a neural signal and relayed to the brain are also reviewed. Finally, we discuss the possible, but not yet clear, role of glucagon in obesity, and as a potential therapeutic tool for the treatment of eating disorders.
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PMID:[Pancreatic glucagon: physiological signal of postprandial satiety]. 802 41

A reduction of postprandial thermogenesis has been described in obesity; insulin resistance and/or decreased sympathetic nervous system activity seem to play the major role in its pathogenesis. On the other hand, a normal energy expenditure during exercise has been reported. At present, the response and the role of catecholamines in energy metabolism during exercise in obesity have not been well clarified yet. The aim of this work was to study the metabolic and hormonal changes caused by intense exercise in obesity. Nine obese subjects and ten normal weight controls were submitted to exhaustive exercise on a cycloergometer. Blood glucose, free fatty acids (FFA), glycerol, lactate, beta-OH-butyrate, insulin, glucagon, plasma growth hormone (HGH), catecholamine plasma levels were assayed before and at the end of exercise, and after a recovery period. The energy cost of exercise was evaluated by indirect calorimetry. In our experiment muscular exercise did not provoke any change in blood glucose and FFA plasma levels in either of our groups. In the obese subjects the insulin plasma levels were higher than in the controls. Glucagon plasma levels did not change. The exercise responses of norepinephrine (NE) (4.28 +/- 0.74 vs 8.81 +/- 1.35 nmol/l; P < 0.01), epinephrine (E) (234.21 +/- 64.18 vs 560.51 +/- 83.38 pmol/l; P < 0.01) and plasma growth hormone (HGH) (134.84 +/- 58.97 vs 825.92 +/- 195.25 pmol/l; P < 0.01) were significantly lower in obese subjects. At the end of exercise, the thermic effect of exercise did not differ between obese and control subjects (0.335 +/- 0.038 vs 0.425 +/- 0.040 kJ/min x kg fat-free mass. Our findings indicate that an impaired counterregulatory hormone response to exercise exists in obese subjects. The thermic effect of exercise does not seem to be affected by either the reduced catecholamine response nor insulin resistance.
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PMID:Impaired counterregulatory hormonal and metabolic response to exhaustive exercise in obese subjects. 932 66

Glucagon-like peptide I (GLP-I) stimulates glucose-dependent insulin secretion and inhibits food intake in the central nervous system. Because leptin reduces food intake but inhibits insulin secretion, we examined leptin action in mice with a null mutation in the GLP-I receptor. Intracerebroventricular leptin administration inhibited food intake in both wild-type and GLP-I receptor (GLP-IR) -/- mice, and daily intraperitoneal administration of leptin for 2 weeks produced comparable reductions in food intake and body weight in control and GLP-IR -/- mice. Glucose tolerance was improved in both wild-type and GLP-IR -/- mice, whether pair fed or leptin treated; however, blood sugars were significantly lower in the leptin-treated GLP-IR -/- mice following oral glucose challenge (P < 0.01). Glucose-stimulated insulin was reduced in both pair-fed and leptin-treated mice (P < 0.01-0.001); however, insulin levels were significantly lower in leptin-treated versus pair-fed GLP-IR -/- mice (P < 0.01). A single leptin injection had no effect on glucose tolerance in GLP-IR -/- mice, but decreased hepatic PEPCK mRNA in both wild-type and GLP-IR -/- mice. The improvement in blood glucose excursion, despite lower levels of glucose-stimulated insulin in lean leptin-treated GLP-IR -/- mice, suggests that leptin may have beneficial effects on control of blood glucose in the absence of obesity. Furthermore, the greater effects of leptin on glucose and insulin in leptin-treated versus pair-fed GLP-IR -/- mice raises the possibility that disruption of GLP-I signaling modifies the sensitivity to leptin in vivo.
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PMID:Leptin sensitivity in nonobese glucagon-like peptide I receptor -/- mice. 939 91

Glucagon-like peptide (7-36) amide (GLP-1) acutely inhibits food and water consumption in rats after intracerebroventricular (icv) administration. To assess the potential for desensitization of these effects, we investigated the effects of chronic icv administration of GLP-1 on food consumption and body weight in Sprague-Dawley (SD) rats and Zucker (fa/fa) obese rats. In vitro functional densensitization of the GLP-1 receptor was not observed after overnight exposure of Rin m5F insulinoma cells to GLP-1 at concentrations up to 10 nM. Administration of GLP-1 to SD rats (30 microg icv twice a day for 6 days) resulted in significant reductions in 24-hour food consumption each day (25 +/- 1%). Continuous icv infusion of GLP-1 for 7 and 14 days significantly inhibited cumulative food consumption and reduced body weight in SD rats. In the genetically obese Zucker rat, chronic dosing with GLP-1 (30 microg icv) once a day for 6 days caused significant reductions in food consumption each day and a reduction in body weight. These results indicate that the GLP-1 pathways in the central nervous system controlling food consumption do not desensitize after chronic exposure to GLP-1 and suggest that agonists of the central GLP-1 receptor may be effective agents for the treatment of obesity.
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PMID:Effect of chronic central administration of glucagon-like peptide-1 (7-36) amide on food consumption and body weight in normal and obese rats. 954 22

The transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) is enriched in liver and adipose tissue and controls the expression of a wide variety of genes coding for important metabolic pathways, including gluconeogenesis and lipid synthesis. To investigate the role of C/EBPbeta on glucose homeostasis, we studied mice with a targeted deletion of the gene for C/EBPbeta-/- mice. Adult C/EBPbeta-/- mice have hypoglycemia after an 18-hour fast, accompanied by lower hepatic glucose production (40% of that of wild-type mice), with no change in plasma insulin and a lower concentration of plasma free fatty acids (FFA). Glucagon infusion during a pancreatic clamp acutely stimulated hepatic glucose production by 38% in wild-type animals, with no change detected in C/EBPbeta-/- mice. Unexpectedly, both the basal and glucagon-stimulated hepatic cyclic adenosine monophosphate (cAMP) levels were lower in C/EBPbeta-/- mice, indicating an essential role for C/EBPbeta in controlling proximal signal transduction. Fasting hypoglycemia was associated with normal levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene expression, however net liver glycogenolysis was impaired in C/EBPbeta-/- mice. FFA release from isolated adipose tissue in response to epinephrine was 68% lower in C/EBPbeta-/- mice than in control animals; however, N6,O2'-dibutyryladenosine (Bt2) cAMP stimulated a twofold increase in FFA release in C/EBPbeta-/- compared with no further increase in wild-type mice. Because a deletion in the gene for C/EBPbeta reduces blood glucose and circulating FFA, it could be an important therapeutic target for the treatment of non-insulin-dependent diabetes and possibly obesity, based on designing antagonists that decrease C/EBPbeta activity.
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PMID:Hypoglycemia and impaired hepatic glucose production in mice with a deletion of the C/EBPbeta gene. 991 32

Palatable cephalic stimuli induce a simultaneous activation of gastrointestinal motility, gastric acid and pancreatic enzyme secretion, as well as, release of the gastrointestinal hormones gastrin and pancreatic polypeptide. Cholinergic neural input is the dominant mediator of these responses with cholecystokinin and gastrin acting as additional stimulatory modulators. Central cholinergic circuits, neuropeptide Y, and thyrotropin releasing hormone are candidate central stimulators of the cephalic phase. There are good arguments for glucagon-like peptide-1 and peptide YY to be physiological inhibitors of cephalic-phase responses with these peptides being released in the intestinal phase of digestion and putatively contributing to termination of the cephalically stimulated pattern. Cephalic-phase responses are used clinically as diagnostic tests to assess completeness of selective proximal vagotomy and to explore autonomic neuropathy. Pancreatic polypeptide secretion with sham feeding is an appropriate test of abdominal vagal function. Cephalically stimulated motor and secretory activity contribute greater than 50% of overall postprandial responses. Pharmacological inhibition of cephalic-vagal stimulation, resulting in reduced food intake, may be a novel approach to obesity management. Glucagon-like peptide-1 is a particular candidate because it inhibits the cephalic phase of digestion, diminishes food intake, and reduces the glycemic excursion after a meal by retarding gastric emptying, stimulating insulin and lowering glucagon release.
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PMID:Nutritional implications of cephalic phase gastrointestinal responses. 1074 9


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