Specific depletion of immunoreactive growth hormone-releasing factor by monosodium glutamate in rat median eminence

Bloch, Bertrand; Ling, Nicholas; Benoit, Robert; Wehrenberg, William B.; Guillemin, Roger

doi:10.1038/307272a0

Cited by 147 publications

(68 citation statements)

References 15 publications

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“…However, some caution is necessary in interpreting the data obtained following MSG treatment. In particular, it should be noted that, although neonatal MSG treatment destroys the majority of the arcuate GH-releasing hormone neurons, this ablation is not selective, with 70 -90% of all neuronal perikarya in the arcuate nuclei being destroyed (1,5). Thus, MSG treatment may also influence adiposity via the disruption of additional hypothalamic pathways, including those regulating orexigenesis and energy homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…Homozygous dw/dw rats bred on an Albino Swiss (AS) background, used in studies 3,5,6, and 8, were housed in the Division of Biological Services, National Institute of Medical Research (NIMR; London, UK), under conditions of 12:12-h light-dark (lights on at 0600), with food and water available ad libitum. The hemizygous Tgr rats, wild-type (WT; AS) littermates, and homozygous dw/dw rats used in studies 1, 2, and 7 were derived from the original colonies at NIMR and were bred in the Transgenic Unit (School of Biosciences, Cardiff University) under conditions of 14:10-h light-dark (lights on at 0500), with food and water available ad libitum.…”

Section: Animalsmentioning

confidence: 99%

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Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency

Davies

Gevers²,

Stevenson³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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This study describes the previously uncharacterized ontogeny and regulation of truncal adipose reserves in the profoundly GH-deficient dwarf (dw/dw) rat. We show that, despite normal proportionate food intake, dw/dw rats develop abdominal leanness and hypoleptinemia (circulating leptin halved in dw/dw males, P Ͻ 0.05) during puberty. This contrasts with the hyperleptinemia seen in moderately GH-deficient Tgr rats (circulating leptin doubled at 6 wk of age, P Ͻ 0.05) and in GH receptor-binding protein (GHR/BP)-null mice (circulating leptin doubled; P Ͻ 0.05). This lean/hypoleptinemic phenotype was not completely normalized by GH treatment, but dw/dw rats developed abdominal obesity in response to neonatal MSG treatment or maintenance on a high-fat diet. Unlike Tgr rats, dw/dw rats did not become obese with age; plasma leptin levels and fat pad weights became similar to those in wild-type rats. In contrast with truncal leanness, tibial marrow adiposity was normal in male and doubled in female dwarves (P Ͻ 0.01), this increase being attributable to increased adipocyte number (P Ͻ 0.01). Neonatal MSG treatment and high-fat feeding elevated marrow adiposity in dw/dw rats by inducing adipocyte enlargement (P Ͻ 0.05). These results demonstrate that, despite lipolytic influence of GH, severe GH deficiency in dw/dw rats is accompanied by a paradoxical leanness. This lean/hypoleptinemic phenotype is not solely attributable to reduced GH signaling and does not appear to result from a reduction in nutrient intake or the ability of dw/dw adipocytes to accumulate lipid. Disruption of preadipocyte differentiation or adipocyte proliferation in the dw/dw rat may lead to the development of this unusually lean/hypoleptinemic phenotype. adipose tissue; bone marrow fat; leptin; dwarfism IT IS WELL ESTABLISHED that growth hormone (GH) deficiency is usually accompanied by an increase in fat accumulation, whereas conditions of GH excess are normally associated with leanness. However, recent studies have revealed that the relationship between GH status and the degree of adiposity is far from simple. For example, although it is assumed that obesity results from the removal of the lipolytic influence of GH (37), it is also recognized that abdominal obesity results in a secondary reduction in GH secretion (35). Similarly, whereas GH replacement in patients with primary GH deficiency leads to specific depletion of intra-abdominal fat (2, 12), the administration of GH to treat obesity in GH-replete individuals does not elicit a consistent reduction or redistribution in body fat (31). Some of these apparent contradictions may be explained by the depot-specific sensitivity of adipose tissue to the lipolytic action of GH (19). The relationship between GH status and adiposity in rodent models of GH deficiency is similarly complex. In the profoundly GH-deficient lit/lit mouse a significant elevation in total proportionate fat mass (14) is reflected in increased inguinal and retroperitoneal fat, whereas parametrial fat is unaffected (26). In addit...

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Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency

Davies

Gevers²,

Stevenson³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Injecting MSG 4 mg/g body weight s.c. at neonatal age, is known to deplete the arcuate nucleus of GHRH neurons (Bloch et al, 1984) thus leading to GH deficiency. Also, our group had previous experience with this model when investigating the growth process in GH deficient animals (Hermanussen et al, 1996).…”

Section: Animal Datamentioning

confidence: 99%

“…Bloch et al (1984) showed that MSG treatment results in the complete loss of growth hormone releasing factor (GRF)-immunoreactive cell bodies within this nucleus and provokes a selective disappearance of GRF-immunoreactive fibres in the median eminence of rats. This technique has routinely been practised to produce functionally hypopituitary animals (Lima et al, 1993) for studies of short-term growth (Hermanussen et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite

Hermanussen¹,

García

Sunder³

et al. 2005

Eur J Clin Nutr

108

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Background: World-wide obesity has risen to alarming levels. We present experimental support for a new and very challenging hypothesis linking obesity, voracity, and growth hormone (GH) deficiency, to the consumption of elevated amounts of the amino-acid glutamate (GLU). Supraphysiological doses of GLU are toxic for neuronal cells. Methods: Human data were obtained from 807 592 German conscripts born between 1974 and 1978, and from 1 432 368 women of the German birth statistics (deutsche Perinatalerhebung) 1995-1997. The effects of orally administered monosodium glutamate (MSG) were investigated in 30 pregnant Wistar rats and their offspring. Pregnant animals either received no extra MSG, or 2.5 g MSG, or 5 g MSG per day, up to the end of the weaning period. In all, 2.5 g, respectively 5 g, MSG accounted for some 10%, respectively 20%, of dry weight of the average daily food ration. After weaning, MSG feeding was continued in the offspring. Findings: Morbid obesity associates with short stature. Average stature of conscripts progressively declines when body mass index increases above 38 kg/m 2 . Also morbidly obese young women are shorter than average though to a lesser extent than conscripts. Oral administration of MSG to pregnant rats affects birth weight of the offspring. Maternal feeding with 5 g MSG per day results in severe birth weight reduction (Po0.01). Weight increments remain subnormal when MSG feeding to the mothers is maintained during weaning (Po0.01). GH serum levels are affected in animals that received MSG during prenatal life via maternal feeding. Animals that are kept on high MSG diet (5 g MSG per day) continue to show serum GH levels that are as low or even lower than those of MSG injected animals (Po0.05), both at day 30 and at day 90 of life. Animals that were kept on medium MSG diet (2.5 g MSG per day) showed low serum GH levels at day 30 of life (Po0.01), but seemed to partially recover before day 90. Almost identical results were observed in IGF-1 serum levels. Oral MSG resulted in dose dependent voracity. The animals fed 5 g MSG per day increased water uptake by threefold (Po0.01), and food uptake by almost two-fold (Po0.01). The influence of MSG is in general more marked in males than in females. Interpretation: GLU is a widely used nutritional substance that potentially exhibits significant neuronal toxicity. Voracity, and impaired GH secretion are the two major characteristics of parenterally administered GLU-induced neuronal damage. GLU maintains its toxicity in animals even when administered orally. Males appear to be more sensitive than females. The present study for the first time demonstrates, that a widely used nutritional monosubstance -the flavouring agent MSG -at concentrations that only slightly surpass those found in everyday human food, exhibits significant potential for damaging the hypothalamic regulation of appetite, and thereby determines the propensity of world-wide obesity. We suggest to reconsider the recommended daily allowances of amino acids and nutritional prot...

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“…Generally, although the present data is in keeping with our previous in vitro results (4) showing a direct GLU-SRIF interaction, we cannot totally exclude the involvement of intermediary steps in vivo particularly since GLU participates in a wide variety of metabolic processes. Growth hormone-releasing factor mediation could be a good candidate since this peptide originates in the arcuate nucleus (27) where an intricate interplay of SRIF/ growth hormone-releasing factor could explain the decreased output of hypothalamic growth hormone-releasing factor concomitant with the increased release of SRIF that has been observed (review in 24).…”

Section: Discussionmentioning

confidence: 99%

Glutamate Peripherally Administered Exerts Somatostatin‐Releasing Action in the Conscious Rat

Benyassi

Tapia‐Arancibia

Arancibia

1991

J Neuroendocrinology

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This study was designed to determine whether glutamate is able to stimulate somatostatin release from in vivo conscious animals when somatostatin release is monitored in unanaesthetized rats stereotaxically implanted with a push-pull cannula in the median eminence. One week after implantation, the median eminence was perfused with artificial cerebrospinal fluid alone or with the addition of either CGS 19755, an N-methyl-D-aspartate (NMDA) receptor antagonist M). The latter (which is able to cross the brain-blood barrier at large doses) was also peripherally administered (1 g/kg ip). Median eminence perfusate samples were collected every 15 min and somatostatin was measured by a sensitive radioimmunoassay. In rats receiving ip glutamate injection, somatostatin release from the median eminence was significantly increased (73.3+ 10.4 versus 24.8k6.2; P

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Specific depletion of immunoreactive growth hormone-releasing factor by monosodium glutamate in rat median eminence

Cited by 147 publications

References 15 publications

Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency

Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency

Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite

Glutamate Peripherally Administered Exerts Somatostatin‐Releasing Action in the Conscious Rat

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