MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure

Abstract

Schoelch, Corinna, Thomas Hü bschle, Ingrid Schmidt, and Barbara Nuesslein-Hildesheim. MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure. Am J Physiol Endocrinol Metab 283: E604-E611, 2002. First published April 23, 2002 10.1152/ajpendo.00439.2001.-Suckling-age rats display endogenous circadian rhythmicity of metabolic rate (MR) with energy-saving, torpor-like decreases, which are sympathetically controlled and suppressed by leptin treatment. We investigated whether neonatal monosodium glutamate (MSG) treatment, known to cause arcuate nucleus damage and adult-age obesity, alters energy balance in the first two postnatal weeks. Continuously recorded MR and core temperatures (Tc) show that MSG treatment disinhibits the periodic, sympathetically controlled, energy-saving drops of Tc and MR. Increased energy expenditure thus explains reduced body fat at normal lean body mass found in MSGtreated pups artificially nourished identically to controls. In MSG-treated mother-reared pups, lean body mass is additionally reduced, suggesting that MSG also reduces suckling. Plasma leptin levels are similar in controls and MSG-treated pups but higher per unit of fat mass in the latter. We conclude that the postweaning development of MSG obesity and depressed thermogenesis are preceded by an early phase of increased energy expenditure with decreased fat deposition during suckling age and hypothesize cell damage in the arcuate nucleus to be involved in both. monosodium glutamate; juvenile rat; arcuate nucleus; obesity; leptin; torpor RODENTS TREATED POSTNATALLY with monosodium glutamate (MSG) develop into obese, stunted adults (4, 29, 37) and have been studied frequently as models for obesity. Postnatal MSG treatment produces central nervous (CNS) neurotoxic cell destruction, with the arcuate nucleus (ARC) as the most sensitive structure (35). With MSG doses sufficient to induce adult-age obesity but low enough to avoid extensive destruction such as retinal lesioning and tail automutilation (3,22,29), the CNS damage is seen in the ventromedial hypothalamus (VMH) and especially the ARC, two brain regions involved in the control of food intake. ARC damage is associated with impaired secretion of the releasing hormones for growth hormone (GHRH) and luteinizing hormone (LHRH) (2, 32), and the resulting changes in adenohypophysial growth hormone (GH) and gonadotropin secretion would explain retarded lean body mass growth and aberrations of gonadal development (19,36). Moreover, in the ARC, neuropeptide Y (NPY) production is almost completely, and proopiomelanocortin (POMC) production distinctly, reduced (1, 16). With these alterations of two peptide systems contributing importantly to the control of food intake and energy expenditure, mice (29, 37) and rats (22) are more or less hypophagic but ultimately become obese. MSG-induced damage of the ARC as the origin of these peptidergic pathways further implies impairment of the neuronal targets for circulating leptin as a hormone ...

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

“…The onset of obesity is associated with low sympathetic and high parasympathetic activities to sustain the accumulation of energy sources, such as fat tissue, decreasing catabolism, and increasing anabolism. Regarding the BW of MSG rats, we observed that they were lighter than respective control animals, which was the characteristic phenotype of this model as described by Remke et al (1988), Dolnikoff et al (2001), and Schoelch et al (2002). Although there were no overweight rats, the MSG-obese rats were found to have more fat pad stores as compared with control animals (Bernardis & Patterson 1968, Bray & York 1998, which was correlated with lower growth hormone (Bakke et al 1978, Acs et al 1982 and reduced basal metabolic rate (Arndt et al 1991).…”

Development of neurological reflexes and motor coordination in rats neonatally treated with monosodium glutamate

“…It leads to degeneration of the neurons in the arcuate nucleus, inner retinal layers and various other brain areas (Olney, 1969;Arees and Mayer, 1970;Heiman and Ben-Jonathan, 1983;van Rijn et al, 1986;Kubo et al, 1993;Ishikawa et al, 1997;Gonzalez-Burgos et al, 2001;Beas-Zarate et al, 2002;Chaparro-Huerta et al, 2002;Pesini et al,. 2004;Stricker-Krongrad and Beck, 2004;Tamas et al, 2004), along with endocrinological, neurochemical and circadian alterations (Lengvari, 1977;Dawson and Lorden, 1981;Miyabo et al, 1985;Mistlberger and Antle, 1999;Schoelch et al, 2002;Urena-Guerrero et al, 2003;Kim et al, 2005). The neurotoxicity of MSG is also reflected in various changes in the motor activity, sensory performance and learning abilities (Iwata et al, 1979;Saari et al, 1990;Fisher et al, 1991;Dubovicky et al, 1997).…”

Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters

“…ARC MSG lesions have been successfully produced in Siberian hamsters, demonstrating that SP-induced changes in hamster body mass, food intake, fur color, and testis mass persist after ARC ablation (16). If MSG ablations in Siberian hamsters mimic the effect on circadian T b min in suckling rat pups (45), then ARC MSG ablations should eliminate photoperiod-dependent torpor in hamsters. Differ-ences in fat reserves between MSG-and saline-treated hamsters raised in SPs were previously nonsignificant (16).…”

“…7 and 26), especially targeting ARC neuropeptide Y and proopiomelanocortin neurons, which both colocalize leptin receptors but have opposing effects on metabolism (9,26,31). MSG ablation of the ARC eliminates "torpor-like" circadian decreases in T b in suckling rats (45).…”