Department of Nutritional Sciences (S.B., D.S.), National Primate Research Center (J.K., R.C., W.N., K.W., S.B.), Department of Physiology (J.K.), and Department of Medicine (R.W.), University of WisconsinMadison, Madison, Wisconsin 53706;Veterans Administration Hospital (R.W.), Geriatric Research, Education and Clinical Center, Madison, Wisconsin 53705; and Department of Molecular Sciences (J.R.), School of Veterinary Medicine, University of CaliforniaDavis, Davis, California 95616
Address correspondence to: Stéphane Blanc, Ph.D., Centre dEcologie et Physiologie Energetiques, Centre National de la Recherche ScientifiqueUnité Propre de Recherche 9010, 23 Rue Becquerel, Strasbourg Cedex 02, 67087, France. E-mail: stephane.blanc{at}c-strasbourg.fr.
To the editor:
We appreciate the interest of Drs. Gallagher, Heshka, and Heymsfield in our recent report on the effect of long-term dietary restriction (DR) on energy expenditure in rhesus monkeys (1). These authors raise an important point regarding the heterogeneity of organs that make up fat free mass (FFM). As these authors know, we are well aware of the potential importance of this heterogeneity (2, 3). We agree that this is a critical point that will need to be tackled in future research. Gallagher and colleagues, however, erred on two important points.
The first point concerns the hypothesis being tested by our experiments. Although the general hypothesis that reduction in energy expenditure during DR may lower the formation of free radicals and extend lifespan was mentioned in the introduction, it was not our primary hypothesis as purported by these authors. Instead, the main objective was to test whether long-term DR induces changes in energy expenditure that are independent of the changes in body composition compartments we could readily assess. To test this hypothesis, we used a regression-based approach to linearly adjust metabolic rate for FFM. This approach takes into account the fact that FFM is a heterogeneous compartment represented by a high oxygen-consuming compartment that does not change much with FFM (represented by an intercept different from zero), and a lower oxygen-consuming compartment that does change with FFM (represented by the ß-coefficient) (4). Although not as sophisticated, this is similar to the assumption made in the recent paper by Heymsfield et al. (5).
The second point seemingly missed is that the adjustment we used accounts for the FFM heterogeneity and is different from the normalization per kilogram that assumes homogeneity in FFM. Although we did not explicitly state that a more sophisticated compositional analysis should be undertaken to understand why the FFM adjusted resting metabolic rate was reduced in restricted animals, this was meant to be implicit when we said further research was warranted. Such studies, however, are still very impractical considering the accuracy and precision of current technologies for imaging of organs. As indicated in their letter, organs that comprise 67% of body mass account for nearly 60% of the REE. To determine whether the 13% reduction in REE that we observed was due to changes in the mass of these organs, we would require an accuracy and precision of 12% of body weight for the high energy expenditure organ mass. Unfortunately, even Heymsfield et al. (5) found that the FFM regression model yielded a higher correlation with resting metabolic rate than the four-compartment model using an assessment of high and low energy expenditure tissues. Given our results, however, such imaging studies are worth pursuing in the restricted animals. Indeed, one of us is pursuing this question and has found that liver mass is rapidly reduced after initiation of DR in rats (Ramsey, J., unpublished data). However, during long-term DR, total and lean body mass losses tend to catch up with the initial rapid drop in liver mass.
We agree that lean mass heterogeneity may play a role in energy expenditure changes with DR. However, until organ mass changes are characterized in rhesus monkeys, we believe that conclusions about the role organ mass alterations may play in the actions of DR are not yet possible. Given our results, such studies are needed once the precision of the technology can be demonstrated.
Received March 26, 2003.
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