WALTER HEYMANN (Cleveland, Ohio): I think that is a fascinating business. To be obese without weighing too much is a frightening thought, and I wonder if you had any information on blood lipids, cholesterol, total lipids, other lipids. Dr. KNITTLE : No, we do not. I do not think that it is such an uncommon thing to be obese and weigh the same as a nonobese individual, if one defines obesity as an excessive accumulation of adipose cells and increase in cell size. H. GHADIMI (Brooklyn, N.Y.): The investigators have prudently avoided extrapolating their results to human infants. Nevertheless, presentation of their data at a pediatric society has the tacit implication that monosodium glutamate (MSG) may have undesirable effects in human infants. To say the least, this conclusion has been repeatedly published following OLNEY'S reports [Science 165: 1028 (1969) and 166: 386 (1969)]. Completely overlooking the difference between humans and other species, the parenteral administration of any substance cannot be accepted as analogous to ingestion. We happen to consume MSG by mouth. Giving an oral load of MSG as high as 600 mg/kg body weight to a human infant did not cause a significant increase in the plasma level of glutamine-glutamic acid. Even the peak values were rather close to the upper limit of normal. This means that the busy crossroad of glutamine-glutamic acid in the liver has no red light; that is, glutamine and glutamic acid are quickly and efficiently metabolized. Obviously, if the route of administration bypasses the liver, the situation is entirely different. My comments on the ‘fattening’ effect of MSG is that alanine and glutamine seem to participate in gluconeogenesis more than other amino acids in rats [PALEOLOGOS, C.; MUNTWYLER, E., and KESNER, L.: Alanine and glutamine levels in rat liver tissue. A direct relationship to gluconeogenic state. PSEBM 132:270 (1969)]. Dr. KNITTLE : We assiduously avoided not mentioning anything about humans, and I really will not be here to defend either the use or lack of use of MSG, either in baby foods or any other foods. I do not think that merely measuring levels of an amino acid circulating in the blood can give you enough information as to what it is doing on a cellular level. I do not want to imply that the giving of MSG is going to make all our babies fat. I merely present this as a very interesting tool which has shown marked alterations in the fat accumulation, and we have seen now in some studies that we do run into a number of individuals whose obesity, at least in its early stage, is exemplified primarily by an increase in cell lipid content, much higher than others of the same age who are of normal weight. I think the whole area of growth and development in critical periods has been very difficult to look at in terms of adipose tissue growth and development. Getting a tool that would directly eliminate the problem of large litter size is difficult because one's harvest here is not too good, and one cannot make very clearly defined critical period determinations. I would like to stress that I think this is a very useful tool. I certainly do not want to extrapolate anything from the rat into people, either in the area of adipose tissue or, for that matter, in the area of the brain. LAURENCE FINBERG (Montefiore Hospital, New York, N.Y.): Have you fed any animals monosodium glutamate rather than injecting them with it? Dr. KNITTLE: We are in the process of doing studies with feeding experiments, but I can only refer you to the article in Science by OLNEY, who has demonstrated quite conclusively that glutamate, asparatate, and cysteine given orally, in high doses, can produce lesions of the brain. Whether this will lead to obesity, I do not know. It is of interest, parenthetically, that in the one animal that we have autopsied, we have found no significant lesions in the arcuate area of the brain, as OLNEY described. So it is possible that obesity may be a phenomenon that is quite separate from the problem of brain damage. I think the possibility of the pancreas entering into this is very important. We are going to try to repeat this in the group treated orally. LYMAN A. PAGE (Stanford School of Medicine, Palo Alto, Calif.): Do you have data on whether the reduced size of other organs is due to reduced cell number? Dr. KNITTLE : We have no data now. We have organs in the deep freeze, and we will be doing DNA and protein ratios to determine cell number and size.
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