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)

The administration of monosodium-L-glutamate (MSG) during the neonatal period is known to result in central nervous system lesions in the arcuate nucleus of the hypothalamus and the retina. Rodents so treated exhibit behavioral deficts and endocrinopathies including obesity, hypogonadism, hypothyroidism, pituitary atrophy, tail automutilation and diminished locomotor activity. Assessment of endocrine status revealed normal serum levels of glucagon, thyroid-stimulating hormone and luteinizing hormone, and diminished levels of thyroid hormones and growth hormone in MSG-treated rats. Prolactin levels were elevated in the glutamate-treated male rats. Within the brain hypothalamic levels of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and somatostatin were unchanged. Measurement of neurotransmitters and neurotransmitter-related enzymes in individual hypothalamic nuclei derived from MSG-treated rats revealed normal levels of norepinephrine, serotonin and glutamic acid decarboxylase, but reduced levels of choline acetyltransferase and dopamine in the arcuate nucleus and median eminence. Histochemical methods for visualization of dopamine and acetylcholinesterase in the mediobasal hypothalamus confirmed these findings. The MSG-treated animals exhibited a normal diurnal rhythm of pineal serotonin N-acetyltransferase activity. These data indicate that the MSG-induced endocrine deficiency syndrome results at least partly from destruction of cholinergic and dopamingeric tuberoinfundibular systems in the hypothalamus.
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PMID:Models of neuroendocrine regulation: use of monosodium glutamate as an investigational tool. 3 35

Genetically obese male Zucker rats (fa/fa) and their lean littermates (Fa/-) were used in this experiment. Fourteen-week-old obese and lean littermates were sacrificed and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) enzymes were assayed in specific brain regions. The assays of these enzymes indicate that obese animals had a significantly lower ChAT activity in the cerebellum, pons, and cerebral cortex and a significant increase in ChAT activity in the thalamus and hypothalamus. Meanwhile, the cerebral cortex, cerebellum, midbrain, thalamus and hypothalamus of the obese animals showed significantly higher AChE activity than their lean littermates. It was concluded from this study that obesity may be associated with changes in the enzymes of the brain cholinergic system.
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PMID:Altered brain cholinergic enzymes activity in the genetically obese rat. 191 66

Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1-29) NH2 100 micrograms iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 +/- 4 vs 44 +/- 16 micrograms/l; mean +/- SEM). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 +/- 5 vs 77 +/- 20 micrograms/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.
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PMID:Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects. 210 45

In obesity the reduced growth hormone (GH) responses to several provocative stimuli including growth hormone-releasing hormone (GHRH) indicate a diminished somatotroph responsiveness but do not distinguish between primary pituitary and hypothalamic pathogenesis. However, it has been shown that the cholinergic system positively influences Gh secretion likely by modulating somatostatin release in a negative way. Thus, the effect of cholinergic activity enhancement by pyridostigmine (PD), an acetylcholinesterase inhibitor, on both basal and GHRH-induced GH secretion was studied in 14 obese subjects (eight adults and six children). Eighteen nonobese subjects (seven adults and 11 children) were studied as controls. In obese subjects the GHRH-induced GH increase was lower than in controls (peak, mean +/- SEM, adults, 9.2 +/- 2.7 v 16.8 +/- 5.7 ng/mL; children, 8.0 +/- 0.8 v 20.3 +/- 4.6 ng/mL) attaining statistical significance only in children group (P less than .02). The PD-induced GH response in the two obese groups was similar to that observed in relative controls (adults, 5.3 +/- 1.0 v 7.4 +/- 1.7 ng/mL; children, 9.6 +/- 1.6 v 13.3 +/- 1.4 ng/mL). PD clearly potentiated the GH response to GHRH in obese subjects, both adults (P less than .05 v GHRH alone) and children (P less than .0005 v GHRH alone). However, the GH responses to PD + GHRH was significantly reduced in obese subjects compared with controls (adults, 18.1 +/- 2.2 v 42.7 +/- 10.7 ng/mL, P less than .05; children, 28.3 +/- 4.5 v 58.2 +/- 7.7 ng/mL, P less than .01). In conclusion, PD is able to potentiate the blunted GH responses to GHRH in obese adults and children, inducing a GH increase similar to that observed after GHRH alone in normal subjects. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in obesity.
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PMID:Effect of cholinergic enhancement by pyridostigmine on growth hormone secretion in obese adults and children. 250 May 77

Serum pseudocholinesterase (PChE) was discovered in 1932. Since this protein mimics many of the catalytic properties of acetylcholinesterase, it has traditionally been referred to as PChE, even though its true biological function is unknown. Serum PChE is synthesized in the liver and secreted into the circulation as a sialated glycoprotein. Although no convincing evidence of biological function exists, a significant number of obese and diabetic patients have elevated levels of PChE. The same phenomenon is found in experimental animal models of obesity, diabetes and hyperlipoproteinemia. Streptozotocin-induced diabetic mice showed increased serum PChE activity concomitant with increased serum triacylglycerol and PChE activity declined with treatment. Iso-OMPA, a nontoxic inhibitor of serum PChE, reduced serum and liver triacylglycerols and serum VLDL in streptozotocin-induced rodent diabetes. These findings suggest that PChE may have a role in VLDL metabolism.
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PMID:Serum pseudocholinesterase and very-low-density lipoprotein metabolism. 793 19

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

Thyrotropin releasing hormone (TRH) administration is known to induce a greater TSH response in normal subjects than in obese subjects. In obesity even GH and PRL response to various stimuli are blunted, presumably because of an augmented somatostatinergic tone in obese subjects. Further studies have shown that pyridostigmine (Pyr), an acetylcholinesterase inhibitor, is capable of augmenting GH in obesity by means of somatostatin inhibition. In order to evaluate the possible interference of an increased somatostatinergic tone on TSH secretion, we studied the TSH response to a TRH bolus in 5 obese children with or without a pyr pretreatment. Similarly, we tested a group of 10 obese adult subjects, with TRH alone or TRH plus pyr administration, 30 min or 60 min before TRH. All subjects had a body weight of 30-50% greater than I.B.W. Our data show that a pretreatment with pyr, 60 min before TRH administration, significantly augments the TSH response in adult obese subjects but not in children; the modality of pyr administration seems to be crucial to evidenciate such an alteration since the pyr pretreatment is not effective when administered 30 min before TRH. The absence of this pyr effect in obese children induces to hypothesize that somatostatinergic tone is differentially modulated in children vs adult obese subjects.
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PMID:Pyridostigmine effects on TSH response to TRH in adult and children obese subjects. 834 46

It is accepted that the tone of the parasympathetic nervous system increases after VMH lesion, whereas the sympathetic tone decreases. To reinforce investigations over outcomes from disturbances of the hypothalamic neuronal systems on peripheral autonomic nerve activity this study determined the acetylcholinesterase (AchE) activity in visceral organs, known as vagal targets, from VMH-lesioned obese rats. It was found that AchE activity was significantly increased in liver, pancreas, and stomach from these animals. However, it was not changed in kidneys, being decreased in spleen. The results suggest that AchE activity is enhanced in vagus innervated tissues to following up the unbalance of the autonomic nervous system as observed in VMH lesion-induced obesity.
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PMID:Acetylcholinesterase activity changes on visceral organs of VMH lesion-induced obese rats. 1700 May 30

Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and lipid peroxides are high whereas those of endothelial nitric oxide are low in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that these diseases are characterized by low-grade systemic inflammation. Recent studies showed that the plasma and tissue activities of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in patients with Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia. As a result of this increase in the activities of enzymes acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway" mediated by acetylcholine acts by inhibiting the production of tumor necrosis factor, interleukin-1, macrophage migration inhibitory factor, and high mobility group box-1 and suppresses the activation of nuclear factor-kappa B expression. ACh is a neurotransmitter and regulates the levels and activities of serotonin, dopamine and other neuropeptides and thus, modulates both immune response and neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by inactivating acetylcholine may enhance inflammation. This suggests that increased plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase seen in various clinical conditions could serve as a marker of low-grade systemic inflammation.
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PMID:Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. 1804 45

Obesity is related to an elevated risk of dementia and the physiologic mechanisms whereby fat adversely affects the brain are poorly understood. The present investigation analyzed the effect of a high fat diet (HFD) on brain steatosis and oxidative stress and the intracellular mediators involved in signal transduction, as well as the protection offered by grape seed and skin extract (GSSE). HFD induced ectopic deposition of cholesterol and phospholipid but not triglyceride. Moreover brain lipotoxicity is linked to an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of glutathione peroxidase and superoxide dismutase activities, depletion of manganese and a concomitant increase in ionizable calcium and acetylcholinesterase activity. Importantly GSSE alleviated all the deleterious effects of HFD treatment. Altogether our data indicated that HFD could find some potential application in the treatment of manganism and that GSSE should be used as a safe anti-lipotoxic agent in the prevention and treatment of fat-induced brain injury.
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PMID:Grape seed and skin extract prevents high-fat diet-induced brain lipotoxicity in rat. 2268 84


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