NEONATAL MSG REDUCES HYPOTHALAMIC DA, BETA-ENDORPHIN, AND DELAYS WEIGHT-GAIN IN GENETICALLY-OBESE (A(VIABLE YELLOW) A) MICE/

Neonatal treatment with monosodium glutamate (MSG) decreases proopiome lanocortin (POMC) peptides and results in obesity. The yellow mouse is a model of obesity induced by the viable yellow (A(vy)) gene at the a gouti locus on Chromosome 2, which results in overproduction of a POMC receptor antagonist. Thus we hypothesized that MSG, when imposed on t he genetically susceptible model, would alter the development of obesi ty. Both yellow obese (A(vy)) and black lean (a/a) males were injected on Postnatal Days 1, 3, 5, 7, and 9 with 2.0 mg/g body weight MSG or saline SC. Their food intake, growth parameters, and neurochemical sta tus were examined. Paradoxically, MSG interacted with the yellow pheno type to delay the rapid rate of weight gain characteristic of this mod el (p < 0.05). Food intake was decreased (p < 0.05) in both phenotypes treated with MSG, as was hypothalamic content of dopamine (p < 0.05) and of the POMC peptide, beta-endorphin (p < 0.001). The yellow obese phenotype was more sensitive than the black lean phenotype to the neur ochemical effects of early postnatal MSG administration. Recent report s suggest the agouti locus protein is an antagonist of the receptor fo r another POMC peptide, melanocyte-stimulating hormone (MSH). Therefor e, the balance of functional activity between various POMC peptides ap pears to be an important factor in the development of both acquired an d genetic obesity.