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

Obese patients (44) were studied on a 320 kcal diet for one to two months. No ECG changes were seen in 43 patients. One patient showed a transient T wave inversion after six weeks dieting, but the significance of this finding is doubtful. We have found a 320 kcal formula diet a safe and effective method of out-patient weight reduction with no patient showing any ECG abnormality in the first four weeks of dieting. ECGs and medical supervision are recommended for patients maintained on low-calorie diets for periods longer than a month. Nitrogen balance reached equilibrium in five to six weeks. Biochemical estimations showed minor changes such as falls in the serum cholesterol and rises in the alkaline phosphatase and bilirubin, but no clinically important changes were observed. One patient on propranolol for hypertension developed postural hypotension and required substantial reduction of medication.
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PMID:Low-calorie-formula diets--are they safe? 727 63

Nitrogen balance has been measured in 25 (16 f, 9m) patients with severe obesity submitted for four weeks to total fasting (TF) or different versions of protein-sparing modified fast (PSMF). The hospitalized patients, divided into four age-matched groups, were treated as follows:Group 1, were submitted to TF; Group 2 were treated by 80 kcal-PSMF (17 g protein=2.6 g N, traces of fat and carbohydrate); Group 3 were submitted to 180 kcal-PSMF (40 g protein = 6.4 g N, 2 g fat, traces carbohydrate) and Group IV, to 80/180 kcal-PSMF (80 kcal during the 1st and 2nd week and 180 kcal during the 3rd and 4th week of treatment). Weight loss was similar (-11 kg) in Gps 1, 2 and 4; lower (-8 kg) in Gp 3. Mean daily Nitrogen loss was significantly lower (P < 0.05) in Gps 3 and 4 than in Gps 1 and 2. Nitrogen loss was significantly reduced from the 3rd week onward in Gps 1 (P < 0.005), 2 (P < 0.05) and 4 (P < 0.002). During 180 kcal-PSMF nitrogen loss was significantly lower (P < 0.005) only when this dietary regimen was preceded by 80 kcal-PSMF for two weeks (Gp 4). These observations suggest a new approach to the treatment of severe obesity by PSMF and show that is is possible to further reduce the early catabolic phase which commonly arises during this type of therapy.
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PMID:Protein-sparing modified fast in the treatment of severe obesity: weight loss and nitrogen balance data. 741 36

Glutamate-induced obesity of Wistar-rats is known to develop under normophagic and normoinsulinemic conditions, although hyperphagia and hyperinsulinemia are common to obese individuals. Rats of this obesity model show retarded growth, reduced mass of some organs, carcass and whole body as well as an extraordinary high fat content, whereas protein content is reduced. In this study, nitrogen (N) balance, urinary excretion of urea-N, ammonia-N, creatine-N and alpha-amino acid-N and plasma free fatty acid concentration of growing, glutamate-induced obese rats were determined. The main results were independent of frame of reference (mmol N/kg body mass; mmol N/kg0.75 metabolic body mass; N in % of nitrogen intake): Nitrogen intake, urinary excretion of alpha-amino acids and nitrogen excretion in faeces were equal between lean and obese rats. Nitrogen excretion in urine was elevated in obese rats, mainly resulting from increased amounts of urea and ammonia. Nitrogen balance was positive in both groups, but reduced in obese rats. These data point to normal digestion of food proteins, but an unusual high oxidative desamination rate of the absorbed amino acids in obese rats. Taking into account the various hormonal and nerval alterations in glutamate-induced obese rats, resulting e.g. in increased hepatic insulin concentration, the retained amino acid carbon should be channelled into hepatic fatty acid synthesis. Really, unfasted and overnight fasted obese rats showed elevated plasma free fatty acid concentrations. Channeling of amino acids into lipogenesis may explain the low muscle mass and striking fat accumulation--despite normophagia and peripheral normoinsulinemia--of growing, glutamate-induced obese Wistar-rats.
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PMID:Reduced, positive nitrogen balance and elevated plasma free fatty acid concentration in growing, glutamate-induced obese rats. 790 47

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

A suppressed growth hormone (GH) response to GH-releasing hormone (GHRH) in both lean and overweight type II diabetics has been reported. Pyridostigmine (PD), an acetylcholinesterase inhibitor, elicits GH secretion when administered alone and enhances the GH response to GHRH in normal subjects. The aim of our study was to evaluate the effect of PD on GHRH-stimulated GH secretion in both lean and obese type II diabetic patients. We studied 16 patients with type II diabetes mellitus (seven lean and nine obese). Eleven nondiabetic subjects (six lean and five obese) served as controls. Each subjects underwent treatment with (1) 120 mg PD orally or (2) 2 tablets of placebo orally, 60 minutes before intravenous (IV) injection of 100 micrograms GHRH-(1-29)NH2. We have found no significant differences in GH responses to GHRH between obese diabetics and obese controls. On the other hand, the absolute GH levels were significantly suppressed in lean type II diabetics compared with lean controls at 15 and 30 minutes after GHRH injection. Obese diabetic subjects had slightly but not significantly decreased GH responses to GHRH+PD compared with obese nondiabetic subjects (8.36 +/- 1.62 v 14.4 +/- 7.62 micrograms/L). Lean type II diabetics showed a blunted GH release after GHRH+PD compared with normal-weight healthy subjects (GH peaks, 15.77 +/- 2.17 v 40.88 +/- 6.17 micrograms/L, P < .05). PD enhanced significantly the GH response to GHRH in obese diabetics, obese controls, and non-obese controls (P < .05), but not in non-obese type II diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II Diabetic patients. 802 15

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

GH induces lipolysis in vivo, increasing plasma free fatty acid (FFA) levels; in turn, FFA are able to reduce GH release, and acipimox, a nicotinic acid analog able to block lipolysis, enhances in normal subjects the GH response to GHRH. Obesity and old age are characterized by a blunted GH response to several stimuli, including GHRH; reports also indicate high plasma FFA levels in obesity and sometimes in the elderly. The aim of this study was to evaluate the possible role of FFA in GH release in obese and elderly subjects. According to a randomized, single blind, cross-over protocol, six healthy subjects, six obese subjects, and six elderly subjects received on 2 different days, with a 1-week interval, placebo or acipimox (250 mg, orally) at 0700 and 1100 h; GHRH [GHRH-(1-44)NH2; 50 micrograms in healthy subjects and in elderly subjects, 100 micrograms in obese subjects] was injected iv at 1300 h, and blood samples for evaluation of plasma FFA, blood glucose, serum insulin (IRI), and serum GH levels were taken from 1200 to 1500 h. Plasma FFA levels were always lower (P < 0.05) after acipimox than after placebo (0.03 +/- 0.01 vs. 0.13 +/- 0.02 g/L in healthy subjects, 0.09 +/- 0.01 vs. 0.27 +/- 0.02 g/L in obese, 0.02 +/- 0.005 vs. 0.17 +/- 0.01 g/L in elderly subjects); serum IRI levels were also lower (P < 0.05) after acipimox than after placebo in the three groups of subjects (16 +/- 3 vs. 30 +/- 5, 120 +/- 30 vs. 181 +/- 32, and 21 +/- 3 vs. 49 +/- 9 pmol/L); both FFA (P < 0.05) and IRI levels (P < 0.05) were higher in obese than in healthy or elderly subjects after placebo and acipimox. Blood glucose levels were not different in the three groups of subjects after either placebo or acipimox. The integrated GH response to GHRH-(GH delta area) was always greater (P < 0.05) after acipimox than after placebo (4677 +/- 633 vs. 1599 +/- 373 in healthy, 1469 +/- 230 vs. 343 +/- 114 in obese, 2304 +/- 759 vs. 325 +/- 133 micrograms/L.120 min in elderly subjects); after both placebo and acipimox, the GH delta area was greater (P < 0.05) in healthy subjects than in obese or elderly subjects. The GH delta area of elderly and obese subjects after acipimox was not different from the GH delta area of healthy subjects after placebo. Changes in GH delta areas were not significantly related to changes in FFA or IRI induced by acipimox; in contrast, absolute values of FFA and IRI as well as basal GH levels were all significantly related to the GH delta area. At multiple regression analysis, FFA was the only significant predictor of GH delta area. These data indicate that acute pharmacological reduction of plasma FFA levels restores the blunted GH response to GHRH commonly observed in obese and elderly subjects: however, when lipolysis is blocked to a similar extent, healthy subjects still show a higher GH delta area than obese or elderly subjects. As FFA are the best predictor of the GH delta area, we suggest that in obesity, the blunted GH release is due to high FFA levels, whereas in the elderly there might be an abnormal sensitivity to normal FFA levels.
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PMID:Restoration of growth hormone (GH) response to GH-releasing hormone in elderly and obese subjects by acute pharmacological reduction of plasma free fatty acids. 892 50

Sibutramine is a noradrenaline and 5-hydroxytryptamine reuptake inhibitor which causes weight loss in laboratory rodents via effects on both food intake and metabolic rate. Sibutramine's effects are predominantly mediated by two pharmacologically-active metabolites (its primary and secondary amines). Sibutramine and its active metabolites do not cause the release of monoamine neurotransmitters and do not have affinity for their receptors. Sibutramine dose-dependently inhibits 24 h food intake in rats by enhancing the natural physiological process of satiety. Sibutramine also stimulates thermogenesis in rats, producing sustained (> 6 h) increases in oxygen consumption of up to 30%. The thermogenic effect of sibutramine results from central activation of efferent sympathetic activity which, in turn, involves activation of beta 3-adrenoceptors. Sympathetic stimulation of brown adipose tissue via beta 3-adrenoceptors is thought to be the cause of the large, 18 fold increase in brown adipose tissue glucose utilization induced by sibutramine. These dual effects of sibutramine on food intake and thermogenesis explain its anti-obesity effect in animals.
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PMID:Sibutramine: a review of the pharmacology of a novel anti-obesity agent. 913 38

Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp7 in conjunction with N-methylation of Phe8 produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Nle-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.
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PMID:Synthesis and biological evaluation of potent, selective, hexapeptide CCK-A agonist anorectic agents. 943 99


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