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European Journal of Clinical Nutrition (2005), 1–7& 2005 Nature Publishing Group All rights reserved 0954-3007/05 $30.00 Obesity, voracity, and short stature: the impact ofglutamate on the regulation of appetite M Hermanussen1, AP Garcı´a2, M Sunder3, M Voigt4, V Salazar2 and JAF Tresguerres2 1Aschauhof, Altenhof, Germany; 2Department of Physiology Medical School, Universidad Complutense, Madrid, Spain;3Volkswirtschaftliches Institute, Ludwig-Maximilian University, Munich, Germany and 4Department Neonatology and PaediatricIntensive Care, Ernst-Moritz-Arndt-University, Zentrum fu¨r Kinder- und Jugendmedizin, Greifswald, Germany Background: World-wide obesity has risen to alarming levels. We present experimental support for a new and very challenginghypothesis linking obesity, voracity, and growth hormone (GH) deficiency, to the consumption of elevated amounts of theamino-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 368women of the German birth statistics (deutsche Perinatalerhebung) 1995–1997. The effects of orally administered monosodiumglutamate (MSG) were investigated in 30 pregnant Wistar rats and their offspring. Pregnant animals either received no extraMSG, 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 forsome 10%, respectively 20%, of dry weight of the average daily food ration. After weaning, MSG feeding was continued in theoffspring.
Findings: Morbid obesity associates with short stature. Average stature of conscripts progressively declines when body massindex increases above 38 kg/m2. Also morbidly obese young women are shorter than average though to a lesser extent thanconscripts. Oral administration of MSG to pregnant rats affects birth weight of the offspring. Maternal feeding with 5 g MSG perday results in severe birth weight reduction (Po0.01). Weight increments remain subnormal when MSG feeding to the mothersis maintained during weaning (Po0.01). GH serum levels are affected in animals that received MSG during prenatal life viamaternal feeding. Animals that are kept on high MSG diet (5 g MSG per day) continue to show serum GH levels that are as lowor even lower than those of MSG injected animals (Po0.05), both at day 30 and at day 90 of life. Animals that were kept onmedium MSG diet (2.5 g MSG per day) showed low serum GH levels at day 30 of life (Po0.01), but seemed to partially recoverbefore day 90. Almost identical results were observed in IGF-1 serum levels. Oral MSG resulted in dose dependent voracity. Theanimals fed 5 g MSG per day increased water uptake by threefold (Po0.01), and food uptake by almost two-fold (Po0.01). Theinfluence 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, andimpaired GH secretion are the two major characteristics of parenterally administered GLU-induced neuronal damage. GLUmaintains its toxicity in animals even when administered orally. Males appear to be more sensitive than females. The presentstudy for the first time demonstrates, that a widely used nutritional monosubstance – the flavouring agent MSG – atconcentrations that only slightly surpass those found in everyday human food, exhibits significant potential for damaging thehypothalamic regulation of appetite, and thereby determines the propensity of world-wide obesity. We suggest to reconsiderthe recommended daily allowances of amino acids and nutritional protein, and to abstain from the popular protein-rich diets,and particularly from adding the flavouring agents MSG.
European Journal of Clinical Nutrition advance online publication, 31 August 2005; doi:10.1038/sj.ejcn.1602263 Keywords: obesity; voracity; short stature; glutamate; arcuate nucleus Correspondence: Professor M Hermanussen, Aschauhof 3, 24340 Altenhof,Germany.
E-mail: hermanussen.aschauhof@t-online.de World-wide obesity has risen to alarming levels (McLellan, Guarantors: M Hermanussen and JAF Tresguerres.
2002). The average weight of German conscripts now Contributors: MS is responsible for conscript data; MV for women’s data; APG, increases by almost 400 g/year. Similar data were obtained VS and JAFT for animal data; and MH for idea, coordination and writing.
Received 20 December 2004; revised 31 May 2005; accepted 7 July 2005 in Austria, Norway, and the UK. Obesity is not a separate problem of only the obese people but appears to be a levels and activation of GLU-receptors after neonatal s.c.
characteristic feature of modern populations as a whole administration of MSG at doses of 4 mg/g body weight and an increase in glial cell reactivity and important changes in Much effort has been spent to understand the patho- NMDA-R molecular composition, with signs of neuronal physiology of obesity. Apart from the rare monogenic causes damage. Kaufhold et al. (2002) were able to prevent the for severe disturbances of the eating regulation – genetic adverse effects of neonatal MSG treatment by concurrent alterations of the ob gene (leptin) (Zhang et al., 1996; Strobel administration of a selective and highly potent noncompe- et al., 1998), the leptin receptor (Clement et al., 1998), a mutation of the melanocortin 4 receptor (MC4R) gene Administering GLU to newborn rodents not only destroys (Farooqi et al., 2000), and mutations in the pro-opiomelano- arcuate nucleus neurones, it also damages other hypotha- cortin (POMC) gene (Krude et al., 1998) – obesity appears to lamic areas. Bloch et al. (1984) showed that MSG treatment show a multifactorial aetiopathogenesis. Disadvantageous results in the complete loss of growth hormone releasing dietary habits, such as overconsumption of fat-rich diets, factor (GRF)-immunoreactive cell bodies within this nucleus excessive use of modern media, in particular television and provokes a selective disappearance of GRF-immuno- viewing (Robinson, 2001), a sedentary lifestyle (Votruba reactive fibres in the median eminence of rats. This et al., 2000), and many other exogenous factors, have been technique has routinely been practised to produce function- made responsible for the development of obesity already in ally hypopituitary animals (Lima et al., 1993) for studies of early childhood. And recently, a new and very challenging short-term growth (Hermanussen et al., 1996).
hypothesis has been added linking obesity, voracity, and That is, GLU-induced neuronal damage results in voracity growth hormone (GH) deficiency to the consumption of and subsequent excessive weight gain, and impaired GH elevated amounts of the amino-acid glutamate (GLU) secretion, the two major characteristics of human obesity.
(Hermanussen and Tresguerres, 2003a, b). Supraphysiological The present study was undertaken to further investigate doses of GLU are toxic for neuronal cells.
the links between obesity, voracity, and GH deficiency. We The arcuate nucleus is the major site of GLU-induced present novel human data supporting evidence that morbid neuronal damage in the hypothalamus. It is situated close to obesity not only associates with GH secretory dysfunction, the bottom of the third ventricle, and is a potent site of but also with short stature, and animal data supporting leptin action. Leptin is produced in the adipose tissue, evidence that GLU toxicity is not limited to parenteral crosses the blood-brain barrier by active transport systems, administration of this amino acid, but that oral administra- and stimulates a specific signalling cascade (Jequier, 2002): it tion of GLU also causes voracity and GH deficiency. The downregulates the orexigenic neuropeptides NPY, agouti similarity between clinical findings in human obesity, and gene-related protein, melanin-concentrating hormone, and effects of oral administration of MSG in laboratory animals orexins, and upregulates POMC and cocaine- and ampheta- strongly support the view that supraphysiological oral loads mine-regulated transcript (CART) mRNA (Elmquist, 2001).
of the amino-acid GLU play a key role in human obesity.
POMC and its post-translational product, alpha-MSH, stimu-late melanocortin receptors (MC3R, MC4R), and therebydownregulate appetite. Arcuate nucleus damage disrupts the signalling cascade of leptin action, thereby impairs theregulation of appetite, and causes voracity (Fan et al., 1997; Body height and body mass index (BMI) were obtained from GLU toxicity is mediated either by inhibiting cystine 807 592 German conscripts born between 1974 and 1978, uptake (Murphy et al., 1990) or receptor-mediated. The aged 19–20 years. BMI ranged between 14 and 48 kg/m2. In N-methyl-D-aspartate receptor (NMDA-R) is fully functional all, 4.7% of the young men were obese with BMI X30 kg/m2, in the rat early in embryogenesis. Xue et al. (1997) found and some 20% overweight with BMI X25 kg/m2. The data that GLU- and aspartate-immunoreactive neurones were were given to us by courtesy of the Institut fu completely absent in the monosodium glutamate (MSG)- zinalstatistik und Berichtswesen, Remagen, Germany. All lesioned arcuate nucleus as well as the ventromedial nucleus conscripts had either completed high school (A–level, lateral to the arcuate nucleus, in mice treated neonatally German: Gymnasium), secondary school (O-level, German: with MSG. Similarly, NMDA-R1-immunoreactive neurones were mostly absent in the MSG-lesioned arcuate nucleus but Hauptschule). We excluded persons who were chronically remained intact in the ventromedial nucleus. There was also ill, or lived under the care of a guardian, and conscripts who a substantial loss of NMDA-R2 immunoreactivity within the did not complete school education (less than 10%). This was arcuate nucleus. Beas-Zarate et al. (2001) measured changes performed on purpose in order to exclude mentally handi- in gene expression of the NMDA-R subunits: NMDA-R1, capped subjects suffering from Down’s Syndrome, Prader- NMDA-R 2A, and NMDA-R 2B in the cerebral cortex, Willi-Syndrome, and other syndromes with short stature and striatum and hippocampus in the brains of rats treated obesity. We assumed that very obese young men had also neonatally with MSG. The authors showed increases in GLU been obese during the final period of adolescent growth.
Obesity, voracity, and short statureM Hermanussen et al Maternal data on body height and weight at the beginning registered daily. Offspring was killed half at day 30 and the of pregnancy from 1 432 368 women were obtained from the German birth statistics (deutsche Perinatalerhebung) 1995–1997 (Voigt et al., 2001). BMI ranged between 12 and 59 kg/m2.
A 10.4% of the young women were obese with BMI X30 kg/ m2, and some 35% overweight with BMI X25 kg/m2. We Half of the animals were killed by decapitation at day 30 and rejected adolescent mothers (o18 years of age), in order to the other half at the end of the observation period at day 90.
exclude those who had not yet reached final height, and Anterior pituitaries were removed, and trunk blood was restricted the sample to persons below the age of 30 years.
collected. Serum samples and anterior pituitaries after being We assumed that very obese young women had also been weighted were kept at À801C, for hormonal determinations obese during the final period of adolescent growth. We are by specific radioimmunoassays (RIA). Pituitary homogenates aware that data obtained from birth statistics are not were obtained by manual glass homogenisers, and processed representative for women in general. Pregnancy provides in saline after thawing in the moment of the measurement.
evidence for unimpaired hypothalamic-pituitary-gonadalfunction. However, large samples of unselected youngwomen are not available in Germany.
Plasma GH levels and pituitary GH content were determined by RIA as previously described (Lima et al., 1993). Pituitary The effects of oral administration of GLU were investigated homogenates were diluted 1:5000 for determination. Reagents in 32 pregnant rats and their offspring up to day 90 of life, in were kindly provided by the National Institute of Diabetes, the animal facilities of the Department of Physiology, Digestive, and Kidney Diseases (NIDDK). The standard used Medical School, Universidad Complutense, Madrid, Spain.
was rat GH RP2. The sensitivity of the curve was 2 ng/ml and The study was conducted in accordance with the principles the Intraassay coefficient of variation was 5.7%.
and procedures outlined in the NIH Guide for the Care and Plasma IGF I concentrations were measured using a Use of Laboratory Animals. Pregnant Wistar rats were kept commercially available rat RIA kit (DSL-2900, Diagnostic under controlled conditions of light (12 h light/12 h Systems Laboratories, Inc.). The sensitivity of the assay was darkness) and temperature (2172C1), and were fed with 20 ng/ml, and the intraassay coefficients of variation for tap water and rat chow (Panlab, Barcelona, Spain) ad libitum.
mean serum concentrations of 323, 772, and 1604 ng/ml At day 14 of pregnancy, the animals were divided into four were 5.9, 6.1, and 3.8%, respectively.
groups (n ¼ 8), and either received no extra MSG (control, Leptin levels were determined by RIA using a commercial kit group 1), or 2.5 g MSG (group 2) or 5 g MSG per day (group (RL-83 K, LINCO RESEARCH), with a sensitivity of 0.5 ng/ml, 3), up to the end of the weaning period. 2.5 g, respectively, and intra-assay coefficients of variation of 2.4% (1.6 ng/ml), 5 g MSG accounted for some 10%, respectively, 20% of dry 4.1% (3.3 ng/ml), 2% (6.8 ng/ml), and 4.6% (11.6 ng/ml).
weight of the average daily food ration. After weaning andgender separation, MSG feeding was continued in theoffspring at the same concentrations.
Group 4 was not given MSG with the chow, and thus Values are expressed as mean7s.e.m. In some cases data were exactly resembled the control group 1, but their offspring subject to log transformation since variances showed a log- was injected with MSG 4 mg/g body weight s.c., on alternate normal distribution. To determine differences in final weight days from day 1 to day 10 of life. Injecting MSG 4 mg/g body or hormonal levels a two-way ANOVA test was performed.
weight s.c. at neonatal age, is known to deplete the arcuate Differences among groups were subjected to a post hoc nucleus of GHRH neurons (Bloch et al., 1984) thus leading to comparison by using Tukey HSD for unequal N-test. Statistics GH deficiency. Also, our group had previous experience with were executed using Statistica program. The significance this model when investigating the growth process in GH deficient animals (Hermanussen et al., 1996). Four mg/gcorrespond to 1 g in a 250 g rat, That is, the s.c. dose was kepta little lower than the dose range of the orally treated groups.
The bioavailability of s.c. administered MSG might behigher, and also different in terms of GLU/glutamine conversion. The offspring of group 4 was important in order Morbid obesity associates with short stature. Regardless of to compare the effects of s.c. vs orally administered MSG.
school education, average stature of conscripts progressively Owing to the existence of two gender groups a total of declines when BMI increases above 38 kg/m2. The same eight experimental groups were obtained with n ¼ 6–9 for applies for fertile women. Morbidly, obese young women are each group of females and males. All litter was weighed at shorter than average (Figure 1) though to a lesser extent than weekly intervals, and the amount of food consumed was with 2.5 g MSG per day (group 2) results in no birth weight Oral administration of MSG to pregnant Wistar rats affects modification as compared to controls, whereas maternal birth weight of the offspring (Figure 2a). Maternal feeding feeding with 5 g MSG per day (group 3) results in severe birthweight reduction (Po0.01). Weight increments remainsubnormal when MSG feeding to the mothers is maintainedduring weaning (Figure 2b) (Po0.01).
Figure 3a, b shows GH plasma levels of the offspring.
As expected, GH plasma levels were low in animals that were neonatally injected with MSG, both at day 30 and atday 90 of life (Po0.05). However, GH serum levels were also affected in animals that had received MSG during prenatal life via maternal feeding. Figure 3b illustrates that animalskept on high MSG diet (5 g MSG per day) 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. The influence of MSG is in general more marked inmales than in females.
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(Figure 4a, b).
Average body height of 807 592 German conscripts born between 1974 and 1978, aged 19 years, and 1 432 368young German women at the beginning of pregnancy (deutschePerinatalerhebung) 1995–1997 (Voigt et al., 2001), vs BMI.
Plasma GH
Log (ng/ml)
Weigth (g)
FEMALES AND MALES
FEMALES AND MALES
Plasma GH
Log (ng/ml)
Weigth (g) 15
FEMALES AND MALES
Mean (7 s.e.m.) plasma concentration of GH at 30 days Mean (7 s.e.m.) birth weight (a) and weaning body (a), and at 90 days (b) of life in normal rats (control), neonatally weight (b) in normal rats (control), neonatally MSG-treated rats MSG-treated rats (injection) and 2.5 g (2.5 g MSG) and 5 g (5 g (injection) and 2.5 g (2.5 g MSG) and 5 g (5 g MSG) MSG oral MSG) MSG oral administered rats (n ¼ 12–18 (a), n ¼ 6–9 (b)). Each administered rats (n ¼ 12–18). Each group includes male and female group includes male and female data since statistical analysis showed data since statistical analysis showed no gender differences.
no gender differences. **Po0.01 vs CONTROL group and *Po0.05 **Po0.01 vs other groups (a), **Po0.01 vs CONTROL þ INJECTION vs CONTROL group (a), *Po0.05 vs CONTROL þ 2.5 g MSG and groups and #Po0.05 vs 2.5 g MSG group (b).
##Po0.01 vs the corresponding FEMALE group (b).
Obesity, voracity, and short statureM Hermanussen et al PlasmaI GF-1
Log (ng/ml)
Water uptake (ml)
FEMALES AND MALES
PlasmaI GF-1
Log (ng/ml)
Food uptake (g)
FEMALES AND MALES
Mean (7 s.e.m.) water (a) and food (b) uptake at 90 days Mean (7 s.e.m.) IGF-1 plasma concentration at 30 days of life in normal rats (control), neonatally MSG-treated rats (a) and at 90 days (b) of life in normal rats (control), neonatally (injection) and 2.5 g (2.5 g MSG) and 5 g (5 g MSG) MSG oral MSG-treated rats (injection) and 2.5 g (2.5 g MSG) and 5 g (5 g administered rats (n ¼ 6–9). **Po0.05 vs CONTROL þ INJECTION MSG) MSG oral administered rats (n ¼ 12–18 (a), n ¼ 6–9 (b)). Each groups; wPo0.05 vs INJECTION group; zzPo0.01 vs 2.5 g MSG group includes male and female data since statistical analysis showed group and ##Po0.01 vs the corresponding FEMALE group (a), no gender differences. **Po0.01 vs CONTROL group (a), **Po0.01 **Po0.01 vs CONTROL þ INJECTION group (b).
vs CONTROL þ 2.5 g MSG and ##Po0.01 vs the correspondingFEMALE group (b).
Figure 5a, b shows the influence of MSG on appetite.
Whereas – in contrast to previous findings (Fan et al., 1997) – Glutamic acid (GLU) is the most common amino acid in MSG-injected animals of this investigation did not show animal protein, and accounts for some 16% of meat protein, significantly increased appetite compared to controls, the and some 20% of milk protein weight. That is, infants who animals kept on medium MSG diet (2.5 g MSG per day), and daily consume up to 5 g/kg body weight of protein (Koletzko, particularly those kept on high MSG diet (5 g MSG per day) 2002), consume as much as 1 g/kg body weight of GLU. GLU demonstrated marked voracity. The animals fed 5 g MSG per is also the physiological ligand of the taste receptor umami, day increased water uptake by threefold (Po0.01), and food the dominant taste of food containing L-GLU, like chicken uptake by almost two-fold (Po0.01). Voracity seems to be MSG- broth, meat extracts, ageing cheese. Umami is responsible dose-dependent and the increase was identical in both genders.
for the immediate sensory effect of MSG on the palatability Leptin values were significantly increased in animals that of food. MSG is used as flavouring agent.
were neonatally injected with MSG, both at day 30 and at However, it has long been known that MSG can also day 90 of life (Po0.05), we found reduced leptin levels in the intoxicate arcuate nucleus neurones. In 1969, Olney and Sharpe reported on brain lesions, obesity, and other Rats orally treated with MSG are smaller and have lower disturbances in mice (Olney, 1969), and in an infant rhesus body weight, than control animals. The gravity index monkey (Olney and Sharpe, 1969) treated with MSG. In (specific weight, measured in air and water) that provides a 1976, Holzwarth-McBride et al. (1976) investigated the relative information about the fat content of animal effect of the MSG induced lesion of the arcuate nucleus by carcasses, however, indicated that MSG fed animals con- measuring catecholamine content in this nucleus and the tained significantly more body fat both at day 30 and at day median eminence of the mouse hypothalamus. The two major characteristics of MSG-induced arcuate nucleus damage hitherto described, are voracity, and impaired GH those found in everyday human food, exhibits significant secretion. However, all of these studies focussed on parent- potential for damaging the hypothalamic regulation of erally administered MSG. We demonstrated that MSG appetite. Although the experimental part of this study was maintains its toxicity even when administered orally.
performed in rodents, and though it remains to be The influence of MSG is in general more marked in males elucidated whether rodents are more sensitive to MSG than than in females. Since MSG has excitotoxic activities and humans, uneasiness remains when considering that world- implies oxidative stress, the gender difference may be wide MSG production has increased from 200 000 (1969), to explained by to the antioxidant activity of estrogens (Ruiz- 270 000 (1979), to 800 000 tons/year in 2001 (Schmid, 2002) Larrea et al., 1997; Cuzzocrea et al., 2001). Estrogens have a (Schmid, 2002, personal communication). First, clinical very important neuroprotective activity (Azcoitia et al., 1999).
evidence in the treatment of very obese subjects further The present investigation was performed in animals not stresses the importance of GLU in the regulation of appetite: older than 90 days. Although at this age, the animals are still Blocking GLU action by antagonising GLU-gated Ca2 þ ion too young to exhibit obvious signs of obesity, MSG fed channels with memantine normalises binge-eating disorders animals contain more body fat than controls, and show within a few hours (Hermanussen and Tresguerres, 2005).
impaired glucose tolerance and insulin resistance (Hirata Other questions remain: is obesity the disease that we are et al., 1997). Macho et al. (2000) found a shift in glucose interested in? Obesity results from a nutritional imbalance.
metabolism towards lipid synthesis in fat tissue, in 3-month- That is, in view of the present findings, we rather have to old rats treated with MSG during the postnatal period, and consider if not voracity is the disease that needs to be demonstrated an attenuation of insulin effect on glucose addressed in the first place. It has been shown that obesity transport due to a lower insulin binding and lower content associates with GH secretory dysfunction. A 24 h integrated of GLUT4 protein. They concluded that early postnatal concentrations of GH were lower in young, obese subjects than administration of MSG exerts an important effect on glucose in young subjects who were lean (Meistas et al., 1982). Veldhuis metabolism and insulin action in adipocytes of adult et al. (1991) examined the mechanisms underlying the reduced animals, indicating that apart from excitotoxic effects in circulating GH concentrations in obese subjects. Obese men the central nervous system, MSG treatment appears to also had fewer GH secretory bursts, and both GH secretion rate and GH burst frequency were negatively correlated with the degree The present findings are alarming, and throw doubts upon of obesity (Veldhuis et al., 1991). However, since obesity results the unscrupulousness of current use of the flavouring agent from a nutritional imbalance, that is, obesity results from MSG. L-Glutamic acid was evaluated by the Joint FAO/WHO voracity – we are now concerned that both the damage in the Expert Committee on Food Additives (JECFA) in 1988. The regulation of appetite, and the impaired GH secretion, result JECFA allocated an ‘acceptable daily intake not specified’ to from world-wide supraphysiological GLU consumption. The glutamic acid and its salts with no additional risk to infants.
fact that large BMI associates with short stature, indicates The Scientific Committee for Food (SCF) of the European towards the possibility that both excessive appetite and growth Commission reached a similar evaluation in 1991. The conclusions of a subsequent review by the Federation of If this be the case, many more questions arise: Do other American Societies for Experimental Biology (FASEB) and the amino acids metabolise into GLU, do other amino acids lead Federal Drug Administration concurred with the safety to similar toxic effects when fed at supraphysiological doses? evaluation of JECFA and the SCF (Walker and Lupien, Is GLU the only ligand that causes NMDA-R-mediated 2000). MSG can be added at concentrations of up to 10 g neuronal damage, or do elevated levels of glycine produce per kg food (European Parliament and Council Directive similarly deleterious effects when binding to the glycine site 95/2/EC). Ca. 3 g MSG are added per kg potato chips (Greiff, of the NMDA-R (the NMDA-R has a glycine-binding site Bahlsen-Lorenz company, personal communication, 2002), (Huggins and Grant, 2005))? Is the NMDA-R the only receptor ca. 3–6 g are added per kg meat products (Kasch, Do that mediates arcuate nucleus damages? Do oral loads of GLU company, 2002, personal communication).
exhibit the same effects than parenteral loads of this amino We used a medium (2.5 g per day per adult animal) and a acid? Much work is still to be performed, but good reasons high (5 g per day per adult animal) MSG diet, accounting for have already been accumulated to reconsider the recom- some 10%, respectively, some 20% of the daily amount of mended daily allowances of amino acids and nutritional food. Yet, rat chow is dried food. Assuming a water content protein, and to abstain from the popular protein-rich diets, of some 70% in an ordinary breakfast sausage, 6 g MSG per kg and particularly from adding the flavouring agents MSG.
meat product equals some 2% MSG in the dry product. Thatis, the medium concentrations of GLU used in our animals,surpassed the concentration that is currently added to modern industrial food, by only the factor five! The present study for the first time demonstrates, that a This work was supported by the Deutsche Gesellschaft fu widely used nutritional monosubstance – the flavouring agent MSG – at concentrations that only slightly surpass and by the European project EURISKED (EVK1-CT2002 -00128).
Obesity, voracity, and short statureM Hermanussen et al by the N-methyl-D-aspartate receptor antagonist dizocilpinemaleate. J Pharmacol Exp Ther 302, 490–496.
Azcoitia I, Sierra A, Garcia-Segura LM (1999). Neuroprotective effects Koletzko B (2002). Beikostprodukte auf Milchbasis. Pa¨diat Prax 62, of estradiol in the adult rat hippocampus: interaction with insulin- like growth factor-I signalling. J Neurosci Res 58, 815–822.
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gru Beas-Zarate C, Rivera-Huizar SV, Martinez-Contreras A, Feria-Velasco (1998). Severe early-onset obesity, adrenal insufficiency and A, Armendariz-Borunda J (2001). Changes in NMDA-receptor gene red hair pigmentation caused by POMC mutations in humans.
expression are associated with neurotoxicity induced neonatally by glutamate in the rat brain. Neurochem Int 39, 1–10.
Lima L, Arce V, Tresguerres JAF, Devesa J (1993). Clonidine Bloch B, Ling N, Benoit R, Wehrenberg WB, Guillemin R (1984).
potentiates the GH response to GHRH in norepinephrine synth- Specific depletion of immunoreactive growth hormone-releasing esis inhibited rats: evidence for an alpha2 adrenergic control of factor by monosodium glutamate in rat median eminence. Nature hypothalamic release of somatostatin. Neuroendocrinology 57, Clement K, Vaisse C, Lablou N, Cabrol S, Pelloux V, Cassuto D et al.
Lu XY (2001). Role of central melanocortin signaling in eating (1998). A mutation in the human leptin receptor gene causes disorders. Psychopharmacol Bull 35, 45–65.
obesity and pituitary dysfunction,. Nature 392, 398–401.
Macho L, Fickova M, Jezova D, Zorad S (2000). Late effects of Cuzzocrea S, Mazzon E, Sautebin L, Serraino I, Dugo L, Calabro G postnatal administration of monosodium glutamate on insulin et al. (2001). The protective role of endogenous estrogens in action in adult rats. Physiol Res 49 (Suppl 1), S79–85.
carrageenan-induced lung injury in the rat. Mol Med 7, 478–487.
McLellan F (2002). Obesity rising to alarming levels around the Elmquist JK (2001). Hypothalamic pathways underlying the endo- crine, autonomic, and behavioral effects of leptin. Int J Obes Relat Meistas MT, Foster GV, Margolis S, Kowarski AA (1982). Integrated Metab Disord 25 (Suppl 5), S78–82.
concentrations of growth hormone, insulin, C-peptide and Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD (1997). Role of prolactin in human obesity. Metabolism 31, 1224–1228.
melanocortinergic neurons in feeding and the agouti obesity Murphy TH, Schnaar RL, Coyle JT (1990). Immature cortical neurones are uniquely sensitive to GLU toxicity by inhibition of Farooqi IS, Yeo GS, Keogh JM, Aminian S, Jebb SA, Butler G et al.
cystine uptake. FASEB J 4, 1624–1633.
(2000). Dominant and recessive inheritance of morbid obesity Olney JW (1969). Brain lesions, obesity, and other disturbances in associated with melanocortin 4 receptor deficiency. J Clin Invest mice treated with monosodium glutamate. Science 164, 719–721.
Olney JW, Sharpe LG (1969). Brain lesions in an infant rhesus Hermanussen M, Danker-Hopfe H, Weber GW (2001). Body weight monkey treated with monosodium glutamate. Science 166, and the shape of the natural distribution of weight, in very large samples of German, Austrian, and Norwegian conscripts.
Robinson TN (2001). Television viewing and childhood obesity.
Int J Obesity Relat Metab Disord 25, 1550–1553.
Hermanussen M, Rol de Lama M, Perez Romero A, Ariznavarreta C, Ruiz-Larrea MB, Leal AM, Martin C, Martinez R, Lacort M (1997).
Burmeister J, Tresguerres JAF (1996). Differential catch-up in body Antioxidant action of estrogens in rat hepatocytes. Rev Esp Fisiol weight and bone growth after short term starvation in rats. Growth Schmid RD (2002). Taschenatlas der Biotechnologie und Gentechnik.
Hermanussen M, Tresguerres JAF (2003a). Does high glutamate intake cause obesity? J Pediatr Endocrinol Metabol 16, 965–968.
Strobel A, Issad T, Camoin L, Ozate M, Strosberg AD (1998). A leptin Hermanussen M, Tresguerres JAF (2003b). Does the thrifty pheno- missense mutation associated with hypogonadism and morbid type result from chronic glutamate intoxication? A hypothesis.
Veldhuis JD, Iranmanesh A, Ho KK, Waters MJ, Johnson ML, Hermanussen M, Tresguerres JAF (2005). A new anti-obesity drug Lizarralde G (1991). Dual defects in pulsatile growth hormone treatment: First clinical evidence that antagonising glutamate- secretion and clearance subserve the hyposomatotropism of gated Ca2 þ ion channels with memantine normalises binge- obesity in man. J Clin Endocrinol Metab 72, 51–59.
eating disorders. Econ Hum Biol 3, 329–337.
Voigt M, Friese K, Pawlowski P, Schneider R, Wenzlaff P, Wermke K Hirata AE, Andrade IS, Vaskevicius P, Dolnikoff MS (1997). Mono- (2001). Analyse des Neugeborenenkollektivs der Jahre 1995–1997 sodium glutamate (MSG)-obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake. Braz J Med Biol Votruba SB, Horvith MA, Schoeller DA (2000). The role of exercise in Holzwarth-McBride MA, Sladek JR, Knigge KM (1976). Monosodium the treatment of obesity. Nutrition 16, 179–188.
glutamate induced lesion of the arcuate nucleus. II Fluorescence Walker R, Lupien JR (2000). The safety evaluation of monosodium histochemistry of catecholamines. Anat Rec 186, 197–205.
glutamate. J Nutr 130 (4S Suppl), 1049S–1052S.
Huggins DJ, Grant GH (2005). The function of the amino terminal Xue YD, Wong PT, Leong SK (1997). Nitric oxide synthase-, N- domain in NMDA receptor modulation. J Mol Graph Model 23 (4), methyl-D-aspartate receptor-, glutamate- and aspartate-immuno- reactive neurones in the mouse arcuate nucleus: effects of neonatal Jequier E (2002). Leptin signaling, adiposity, and energy balance. Ann treatment with monosodium glutamate. Acta Neuropathol (Berlin) Kaufhold A, Nigam PK, Dhir RN, Shapiro BH (2002). Prevention of Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM latently expressed CYP2C11, CYP3A2, and growth hormone (1996). Positional cloning of the mouse obese gene and its human defects in neonatally monosodium glutamate-treated male rats

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