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

Twelve antidepressant drugs, currently in clinical use, were screened for thermogenic properties on the basis of their ability to stimulate the activity of the sympathetic nervous system via an inhibitory effect on noradrenaline reuptake into the sympathetic neurons. Drug screening was carried out on mice made obese by hypothalamic lesioning using monosodium glutamate. Preliminary experiments, based on changes in body weight and food intake in response to increased doses of the drugs, indicate that most of the twelve antidepressants possess thermogenic potential. In particular, butriptyline, protriptyline and nortriptyline were most effective in causing marked losses in body weight without altering the food intake of the mice. The potent anti-obesity thermogenic properties of these three antidepressants were confirmed during a 10-week energy balance study involving measurements of energy expenditure over the entire period by the comparative carcass method, as well as by measurement of 24 h oxygen consumption. These studies indicate that the methodology employed in the preliminary screening is valid for identifying drugs with thermogenic potential, and demonstrate that many antidepressants currently in clinical use have marked thermogenic properties, and could therefore influence the nutritional status of patients under drug therapy.
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PMID:Screening of drugs for thermogenic anti-obesity properties: antidepressants. 359 17

Neonatal administration of monosodium glutamate (MSG) results in severe adenohypophyseal endocrine malfunction as a result of hypothalamic neurotoxic lesioning. The present study examined the effects of administration of MSG on the neurohypophyseal vasopressinergic (AVP) system and systolic blood pressure (SBP) in adulthood. Monosodium glutamate or hypertonic sodium chloride was administered to male and female rat pups on days 1, 3, 5, 7 and 9 after birth. MSG treatment produced several features characteristic of the MSG-toxicity syndrome, including obesity, anterior pituitary dysgenesis and hypogonadism. However, MSG did not alter neurohypophyseal AVP profiles: AVP content of the posterior pituitary and microdissected regions of the hypothalamus and brainstem were similar in MSG-treated and control rats. Furthermore, MSG treatment did not alter water intake, serum AVP concentration, or the ability to reduce urine output in response to water deprivation. Thus, despite insult to adenohypophyseal function by neonatal administration of MSG, the neurohypophyseal AVP system remained functionally intact. In contrast, neonatal treatment with MSG altered SBP in a sex dependent manner. Female MSG-treated rats, unlike male MSG-treated rats, exhibited consistent systolic hypotension when compared with the NaCl-treated or non-treated control rats at 6, 9 and 12 weeks of age. Despite this chronic hypotension in MSG-treated female rats, heart rate was not altered and serum AVP was not elevated. These observations suggest a resetting of the baroreflex, attributable to neonatal administration of MSG.
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PMID:Monosodium glutamate neurotoxicity: a sex-specific impairment of blood pressure but not vasopressin in developing rats. 375 44

Treatment of neonatal mice with large, repeated doses of monosodium L-glutamate (MSG) produces a syndrome of obesity and endocrinological dysfunction generally attributed to a hypothalamic lesion. We have used single injections of MSG, administered on postnatal day four, to explore the lower end of the dose-response curve for this toxin. Major features of the MSG syndrome including hypophagia, obesity, hypoactivity, reduced pituitary protein content, decreased ovarian weight, delayed puberty and elevated plasma corticosterone levels were obtained at the highest dose. Of the variables measured, feeding disturbances and reduced pituitary and ovarian weights were the most sensitive indicators of damage. The extent of damage produced in the arcuate nucleus of the hypothalamus increased with increasing dose. A prominent lesion was also detected in the medial preoptic area of animals receiving the highest dose. Damage was not evident in other diencephalic structures associated with body weight regulation. Since little is known about the mechanisms underlying MSG obesity, a second study examined the contribution of ovarian hormones to obesity in MSG treated mice. Ovariectomy increased the body weights of animals injected with low but not high doses of MSG, suggesting that a reduction in ovarian function may contribute to the MSG obesity syndrome in the female. Measurement of hypothalamic monoamines and metabolites in these mice indicated that as with repeated doses of MSG, single injections of the toxin reduced hypothalamic dopamine levels. DOPAC levels were unchanged.
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PMID:Behavioral and endocrinological effects of single injections of monosodium glutamate in the mouse. 378 12

The growth pattern of visceral organs was investigated in monosodium L-glutamate (MSG)-treated obese mice with hypothalamic lesions. Male Jcl-ICR strain mice were subcutaneously injected with MSG, 2 mg/g of body weight daily, for five days after birth. The MSG-treated mice became obese after 4 weeks of age. According to patterns of weight gain compared with those in the control mice, the visceral organs in the MSG-treated mice were classified into three groups as follows: The first group of organs (heart, lungs, spleen, pancreas, kidneys, testes, brain and submandibular glands) remained absolutely lower in weight throughout their growth. The second group of organs (liver and stomach) was low in weight until 12 weeks of age, but became identical to that of the control mice after 16 weeks of age. The third group of organs (epididymal fat, small intestine and colon) showed lower weight until 4 weeks of age and were significantly heavier than those in the control mice after 8 weeks of age. The heart in the first group of organs apparently had hypertrophic muscle cells after 8 weeks of age and became significantly hypoplastic due to decreased cell production as was revealed by the continuous suppression of mitotic activity and DNA synthesis by [3H]thymidine autoradiography. The liver in the second group of organs became significantly hypoplastic due to decreased cell production and showed the same weight with the control mice due to the development of fatty liver. The small intestine in the third group of organs became hypoplastic due to decreased cell production in the crypts until 4 weeks of age, and became hypertrophic and hyperplastic by the acceleration of cell production in the crypts from 4 to 8 weeks of age. From these findings, in the MSG-treated mice with specific growth patterns of visceral organs, it is suggested that low energy expenditure results in a relatively excessive energy supply and leads to obesity, because most of the important organs with major physiological functions became hypoplastic. Moreover, it seems that hypertrophy and hyperplasia of the intestine suggest a possible acceleration of the absorptive function.
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PMID:Morphological and cell proliferative study on the growth of visceral organs in monosodium L-glutamate-treated obese mice. 380 54

Subcutaneous administration of monosodium glutamate (MSG) to neonatal female non-obese diabetic (NOD) mice resulted in obesity associated with stunting and hyperinsulinemia. However, the cumulative incidence of diabetes mellitus at 25 weeks of age in the MSG group was significantly lower than in the control group (10.3% vs. 43.6%, P less than 0.005). The immunoreactive insulin content of the pancreas from the 13- to 20-week-old MSG-treated mice was higher than that of the control mice (P less than 0.005). Immunohistochemistry showed that the number of pancreatic B-cells was well preserved and insulitis was attenuated in the MSG-treated mice. Plasma corticosterone and 3, 5, 3'-triiodothyronine levels were elevated in the MSG group. These results suggested that, by the MSG treatment, the B-cell functions were maintained through the modification of the degenerative process of the islets in the NOD mouse.
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PMID:Decreased incidence of diabetes mellitus by monosodium glutamate in the non-obese diabetic (NOD) mouse. 390 73

Norepinephrine (NE) turnover, an index of sympathetic nervous system (SNS) activity, was measured in interscapular brown adipose tissue (IBAT), heart and pancreas of 3-weeks-old pre-obese monosodium-L-glutamate (MSG) mice and at 6-weeks-old mildly obese MSG mice. In IBAT, rates of NE turnover were slower not only in 3-weeks-old MSG mice but also in older obese MSG mice than in their saline controls. In heart, rates of NE turnover were slower in 6-weeks-old mildly obese MSG mice, but not in pre-obese MSG mice. No significant difference in NE turnover in pancreas was observed at either age. The low NE turnover in IBAT of MSG-treated mice prior to the onset of gross obesity suggests that low SNS activity may be an initial contributor to their high energy efficiency and resultant obesity.
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PMID:Reduced norepinephrine turnover in brown adipose tissue of pre-obese mice treated with monosodium-L-glutamate. 397 2

We have studied thermoregulatory thermogenesis in mice rendered obese by neonatal administration of monosodium glutamate (MSG) and in saline treated controls. At 12 weeks of age MSG-treated mice maintained on a chow diet and housed at 24 degrees C, exhibited hypertrophy of brown adipose tissue (BAT) compared to controls (65% increase in wet weight and lipid content, no difference in DNA content). Acute cold exposure (4 degrees C for two hours) resulted in a significantly greater fall in core temperature in MSG-treated than control mice. After cold exposure to 4 degrees C for six hours, control animals mobilized BAT lipid whereas MSG-treated animals did not. Both groups showed comparable increments in oxygen consumption in response to exogenous norepinephrine. The above changes were qualitatively the same for both male and female animals. The following conclusions were reached: (1) MSG-treated mice have defective cold induced thermogenesis, indirect evidence suggests this results from impaired activation of thermogenic mechanisms in BAT; (2) the defect responsible for this lies extrinsic to BAT; and (3) the quantitative significance of defective thermoregulatory thermogenesis for the development of obesity in these mice is uncertain.
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PMID:Defective thermoregulatory thermogenesis in monosodium glutamate-induced obesity in mice. 401 May 23

In newborn mice subcutaneous injectionis of monosodium glutamate induced acute neuronal necrosis in several regions of developing brain including the hypothanamus. As adults, treated animals showed stunted skeletal development, marked obesity, and female sterility. Pathological changes were also found in several organs associated with endocrine function. Studies of food consumption failed to demonstrate hyperphagia to explain the obesity. It is postulated that the aduls syndrome represents a multifacted nueroendocrine disturbance arising from the disruption of developing nueral centers concered in the mediation of endocrine function.
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PMID:Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. 577 21

Immunocytochemical analysis using antisera generated against the brain peptide somatostatin (SRIF) was examined in the brain of normal mice and in mice with chemical lesions of the arcuate nucleus produced neonatally by the administration of monosodium glutamate (MSG). In the normal mouse brain, SRIF immunoreactivity was seen in perikarya of the preoptic and hypothalamic periventricular nuclei. The normal distribution of SRIF fibers was apparent in several hypothalamic nuclei including the arcuate nucleus and in the internal and external zones of the median eminence. Extrahypothalamic sites of SRIF immunoreactive neurons and fibers were also observed throughout the telencephalon. At 60 days of age, certain neuroendocrine deficiencies, including growth parameters and obesity, were apparent in MSG-treated newborn mice. Analysis of SRIF projections in the brain of MSG-treated mice demonstrated a neurotoxic effect on arcuate neurons and a loss of SRIF projections to this region as well. Other components of the SRIF system in brain appeared unaffected. SRIF fibers of the arcuate region seem to originate from neuronal perikarya of the periventricular nucleus suggesting that MSG-induced endocrine deficiencies may be due to SRIF interactions at the level of the arcuate nucleus.
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PMID:Distribution of somatostatin in the mouse brain: effects of neonatal MSG treatment. 612 Jul 49

The plasma lipids and lipoproteins of rats developing obesity after neonatal administration of monosodium glutamate (MSG) were compared with those obtained from controls. The MSG-treated rats, in addition to being stunted and having enlarged adipose tissue stores, showed reduced body weight and food intake. These rats revealed a marked increase of plasma triglyceride and a slight but significant increase of phospholipids in both male and female. There was no significant difference in plasma cholesterol between MSG-treated rats and controls. The lipids and protein concentrations of very low density lipoprotein (VLDL: d less than 1.006 g/ml) were significantly greater in the MSG-treated rats than in the controls. There were no changes in the composition of these increased VLDL, which indicated that the number of VLDL particles was increased. Plasma triglyceride and lipids components of VLDL were significantly greater in males than in females. In spite of hypophagia, both male and female MSG-treated rats had higher plasma glucose levels than sex-matched controls. Plasma insulin level was higher in male MSG-treated rats (49.3 +/- 6.6 microU/ml [s.e.]) than in female MSG-treated rats (14.3 +/- 3.2 microU/ml) or in male control rats (34.6 +/- 6.6 microU/ml). These results suggested that hyperinsulinemia plays an important role in the increase of VLDL observed in the MSG-treated male rats.
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PMID:Plasma lipoproteins of monosodium glutamate-induced obese rats. 639 19


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