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

Obese Zucker (fa/fa) rat skeletal muscle is characterized by a reduced rate of muscle protein deposition possibly due to alterations in amino acid transport. The purpose of the present study was to investigate alanine transport in plasma membrane vesicles from skeletal muscle of lean and obese Zucker rats, facilitating the study of alanine transport independent of cellular metabolism. Initial rates of alanine transport were measured in the presence and absence of Na using a rapid filtration technique, and the properties of membranes from control and maximally insulin-treated lean and obese Zucker rats were studied. For lean rats, the maximal stimulation (Vmax) for Na-dependent alanine transport was 207 pmol.mg-1.s-1, and the half-maximal affinity constant (K1/2) was 2.3 mM. Insulin treatment increased the Vmax to 387 pmol.mg-1.s-1 with no changes in K1/2. For the obese rats, the Vmax for Na-dependent alanine transport was 248 pmol.mg-1.s-1, and the K1/2 was 2.8 mM. These values were not changed by insulin treatment. Thus Na-dependent alanine transport in obese rat skeletal muscle is resistant to stimulation by insulin; this alteration may contribute to the abnormal muscle protein metabolism observed in these animals.
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PMID:Insulin and Na-dependent alanine transport in skeletal muscle of obese Zucker (fa/fa) rats. 781 Jul 71

The changes in alanine turnover were determined in Zucker rats, which were either genetically obese (fa/fa) or rendered obese by dietary treatment (cafeteria fed). The whole body rate of alanine turnover was higher in genetically obese rats than in rats in which obesity was induced by diet (cafeteria). This is possibly due to variations in the rate of the amino acid incorporation into proteins, since the rate of whole body alanine degradation is the same for both groups. Thus, the different pattern followed by alanine turnover rate in these types of obese animals reflects the differences in the nitrogen economy of these animals, pointing to a higher alanine utilization in the genetically obese animals and a conservative management of alanine in the cafeteria-fed animals.
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PMID:Changes in alanine turnover rate due to nutritional and genetic obesity in the rat. 784 26

The study of intestinal and hepatic uptake of amino acids by obese rats has been the main objective of this work. The obese animals used were either from genetic or from nutritional basis. In fed state, the intestinal release of amino acids was higher in obese animals than in lean ones (around the double values), but nutritionally and genetically obese rat showed a related pattern, specially for the case of alanine (increased release in relation to controls by a factor of 10). The higher alanine release by intestine is not reversed by 12-h food deprivation. The hepatic availability was also higher in obesity models than in lean animals (increases over 30%). However, the hepatic uptake was increased in genetically obese animals (more than 35%) and decreased in nutritionally obese animals (more than 40%), especially due to alanine uptake (2419, 1100 and 3794 nmols/min/g protein in lean, Diet-ob and fa/fa animals respectively). In obese animals the food deprivation tended to normalize the hepatic uptake of alanine. The differences in alanine uptake between both types of obesity may reflect the differences of urea synthesis.
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PMID:Splanchnic amino acid pattern in genetic and dietary obesity in the rat. 785 38

Growth hormone (GH) secretion is regulated by a complex system of central and peripheral signals. Recently, a new GH-releasing hexapeptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) called GHRP-6 which specifically releases GH has been studied. In the present work the mechanism of action of GHRP-6 has been addressed in experimental animal models as well as in obese subjects. GHRP-6 releases GH independently of the hypothalamic factors GHRH and somatostatin and is a powerful GH releaser in obesity.
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PMID:Regulation of growth hormone secretion by the growth hormone releasing hexapeptide (GHRP-6). 792 Sep 95

Patients with primary hypercholesterolemia and established coronary artery disease (CAD) with additional associated risk factors for atherosclerosis are considered for lipid-lowering drug therapy at lower levels of total and/or low-density lipoprotein cholesterol (LDL-C) than are patients with isolated hypercholesterolemia. As regards prevention of cardiovascular morbid events, high-risk patients are expected to receive the most benefit from lipid-lowering treatment. Thus, it is of interest to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fluvastatin, a new, wholly synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in patients at high risk. A retrospective analysis was based on data from controlled clinical trials in which 1,815 patients were treated with fluvastatin at a daily dose of > or = 20 mg and 783 patients received placebo. Of the fluvastatin-treated patients, 328 (18.1%) had CAD compared with 136 (17.4%) patients taking placebo. Within these groups, 186 fluvastatin patients and 75 placebo patients had at least one of the following additional risk factors: hypertension, obesity, and/or fasting blood glucose levels above the upper limit of normal (ULN). Patients at high risk, as defined above, were compared with patients without CAD or any risk factors (fluvastatin, n = 837; placebo, n = 375). The effect of 40 mg of fluvastatin on LDL and high-density lipoprotein cholesterol (HDL-C), and triglycerides tended to be enhanced in patients at high risk (HR) compared with those at low risk (LR). Changes from baseline in HR patients were: LDL-C, -26.6%; HDL-C, 6.4%; triglycerides, -13%. Changes in LR patients were: LDL-C, -24.8%; HDL-C, 4.4%; triglycerides, -6%. All of these changes were highly significant (0.001 < p < 0.01). No patient in the HR group experienced a confirmed (measured on two consecutive occasions) increase > 3 x ULN in aspartate (ASAT) or alanine (ALAT) aminotransferases, nor any notable increases in creatine kinase > 10 x ULN. The tolerability of fluvastatin, as assessed by analysis of adverse events, was not consistently influenced by concomitant high risk. This exploratory analysis of the efficacy and safety profile of fluvastatin in patients at high risk for atherosclerosis suggests that such treatment is efficacious, safe, and well tolerated. The observed tendency toward an improved efficacy in the high-risk group will need further confirmation using data from prospective studies in such patients.
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PMID:Fluvastatin in primary hypercholesterolemia: efficacy and safety in patients at high risk. An analysis of a clinical trial database. 801 71

Membrane vesicles from the small intestine brush border were obtained and used to determine the possible effects of genetic or nutritional obesity on L-alanine uptake. Membrane vesicles from Zucker fa/fa obese rats and cafeteria diet-fed Zucker Fa/? rats showed the same characteristics as those of standard diet-fed lean animals. All preparations showed sodium-dependent transport as the main pathway for L-alanine uptake within the substrate concentration range tested. The apparent substrate affinity constant (Km) values and the pattern of inhibition of Na(+)-dependent L-alanine uptake by other amino acids (L-leucine and L-glutamine), suggests that system B involved in the transport of dipolar amino acids (formerly named Neutral Brush Border System) participates in the Na(+)-dependent transport of L-alanine. The affinity constant (Km) for L-alanine was essentially the same for all the groups studied (in the range of 10 mM). However, there was a higher (P < 0.05) maximal capacity (Vmax) in preparations from diet-induced obese animals (cafeteria diet) than that of genetically obese rats. These results indicate that either nutritional or genetic obesity may modify the capacity but not the affinity of transport systems for L-alanine uptake in the brush border of rat small intestine.
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PMID:L-alanine transport in small intestine brush-border membrane vesicles of obese rats. 801 96

1. The relationship between hypertension, obesity, non-insulin-dependent diabetes mellitus and various parameters of glucose metabolism was studied. Lean and obese rats of the SHR/N-cp and LA/N-cp congenic strains were studied at four months of age. 2. Tritium and 14C-labeled glucoses were infused in one set of rats while tritiated water and 14C-labeled alanine were infused in a second group. 3. Glucose oxidation, turnover, conversion to glycogen, fatty acid synthesis, and alanine conversion to glucose were determined, as were blood pressure, pulse pressure and heart rate. 4. The presence of obesity influenced body weight, body fat, de novo fatty acid synthesis, organ weights, glucose mass, glucose oxidation, glucose synthesis, glucose carbon turnover and pulse pressure. 5. It had no effect on glycogen synthesis, tissue glycogen levels, blood glucose, glucose space, or blood pressure. 6. Strain differences were observed in final body weight, organ weights, blood pressure, pulse pressure, hepatic fatty acid synthesis, glucose mass, glucose space, glucose synthesis, liver glycogen levels and glucose conversion to muscle glycogen. 7. Strain-phenotype interaction effects were observed on glucose incorporation into hepatic glycogen, Cori cycle activity, hepatic de novo fatty acid synthesis, final body weight, fat pad weight, heart weight, and mean arterial pressure. 8. These results suggest that although obesity and hypertension are genetic traits in these rats, these traits are independent in their influence on the metabolism of glucose and the development of non-insulin-dependent diabetes mellitus.
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PMID:Glucose turnover in lean and obese rats of the SHR/N-cp and LA/N-cp strains. 840 55

GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.
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PMID:Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. 847 88

GH secretion in response to provocative stimuli is blunted in obese patients. On the other hand, increases in plasma free fatty acids (FFA) inhibit the GH response to a variety of stimuli, and FFA levels in plasma are increased with obesity. To ascertain whether FFA might be responsible for the GH secretory alterations of obesity, we studied spontaneous and stimulated GH secretion in 31 obese patients after FFA reduction by acipimox, a lipid-lowering drug devoid of serious side-effects. Each subject underwent two paired tests. In one, acipimox was administered orally at a dose of 250 mg at -270 min and at a dose of 250 mg at -60 min; in the matched test, placebo was given at similar intervals. To induce GH release, three stimuli acting through different mechanisms were used: pyridostigmine (60 mg, orally, at -60 min), GHRH (100 micrograms, iv, at 0 min), and GHRH plus GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; both at a dose of 100 micrograms, iv, at 0 min). GH secretion was analyzed as the area under the secretory curve (AUC; mean +/- SE; micrograms per L/60 min). Acipimox pretreatment alone (n = 13) induced a large reduction in FFA levels compared with placebo treatment. The FFA reduction led to a slight GH rise (AUC, 123 +/- 47), not different from that in the placebo group (61 +/- 15). In the pyridostigmine-treated group (n = 6), the acipimox-pyridostigmine AUC (408 +/- 107) was significantly higher (P < 0.05) than that in the placebo-pyridostigmine group (191 +/- 25). Furthermore, the GHRH-mediated (n = 6) AUC of GH secretion in the placebo test (221 +/- 55) was tripled by FFA reduction due to acipimox, with an AUC of (691 +/- 134; P < 0.05). Even the most potent GH stimulus known to date, i.e. GHRH plus GHRP-6, was enhanced by FFA suppression. In fact, the placebo-GHRH-GHRP-6 AUC was 1591 +/- 349, lower (P < 0.05) than that in the acipimox-GHRH-GHRP-6 test (2373 +/- 242). The enhancing effects of FFA lowering on GHRH-mediated and GHRH- plus GHRP-6-mediated GH release were synergistic. These results indicate that in obese subjects, unlike normal weight subjects. FFA reduction per se does not stimulate GH secretion. A reduction in FFA with acipimox, however, increased pyridostigmine-. GHRH-, and even GHRH- plus GHRP-6-mediated GH release, suggesting that FFA reduction operates through a different mechanism from that of these three stimuli. The abnormally high FFA levels may be a contributing factor for the disrupted GH secretory mechanisms in obesity.
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PMID:Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression. 877 50

This study compared the effects of exogenous pyruvate and lactate on the serum levels of pyruvate, lactate, glucose, alanine, and insulin, as well as the activity of hepatic pyruvate dehydrogenase (PDH) in strains of rat that were either sensitive [Osborne-Mendel (OM)] or resistant (S5B/Pl) to high-fat diet-induced obesity. Serum pyruvate and lactate were significantly higher and glucose lower in ad libitum-fed OM rats, but these differences disappeared after an 18-h fast. The increase in pyruvate and lactate after exogenous pyruvate administration was significantly greater in S5B/Pl rats than OM rats. There were no differences in serum alanine with strain or diet. The total PDH activity was similar across strains and diets but the proportion of PDH in its activated form (PDHa) was decreased in ad libitum-fed S5B/Pl rats. Pyruvate injection increased insulin and hepatic PDHa activity in OM rats fed both high- and low-fat diets, but these responses were greatly attenuated or absent in S5B/Pl rats. The data are consistent with the hypothesis that modulation of carbohydrate oxidation by PDH may be related to susceptibility to obesity when rats are fed a high-fat diet.
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PMID:Pyruvate and hepatic pyruvate dehydrogenase levels in rat strains sensitive and resistant to dietary obesity. 878 Feb 12


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