Dubious Assumptions Underlying the Adjustment of Metabolic Rates for Changes in Fat-Free Mass

Dympna Gallagher, Stanley Heshka and Steven B. Heymsfield

Obesity Research Center, St. Luke’s-Roosevelt Hospital, and Columbia University Institute of Human Nutrition New York, New York, 10025

Address correspondence to: Dympna Gallagher, Ed.D., St. Luke’s Roosevelt Hospital, Obesity Research Center, Columbia University, 1090 Amsterdam Avenue, 14th Floor, New York, New York 10025. E-mail: dg108{at}columbia.edu.

To the editor:

An article (1) with accompanying editorial (2) published recently in this journal provides new data and a comprehensive discussion of energy expenditure in dietary-restricted (DR) animals. The aim was to provide evidence bearing on the hypothesis that reduced oxygen consumption may lower the formation of reactive oxygen species (1), thereby reducing oxidative damage and extending lifespan. This hypothesis implies that oxygen consumption in DR animals is reduced beyond that expected on the basis of reduced body size or altered body composition. The resulting analysis found that after adjusting for the amount of fat-free mass (FFM), resting energy expenditure (REE) was 13% lower (-250 kJ/d) in DR animals. These findings were interpreted to mean that DR lowers REE independent of DR-induced changes in body composition. The editorial (2) recommends regression-based approaches to adjusting metabolic data when concomitant changes in body composition occur.

It is quite certain that adjusting changes in energy expenditure for changes in FFM can provide no evidence of rate of oxygen flux at the cellular level, which is the level at which oxygen flux must decrease if exposure to free radicals is to be lessened. Although normalizing for FFM may be preferable to using body weight or body surface area, FFM is a construct that lumps together diverse fluids, organs, and tissues with different cellular oxidative requirements. Heterogeneity in heat-producing tissues that make up body mass and FFM has long been recognized (3, 4, 5, 6), and the existence of large between-organ differences in the rates of energy flux is well established (3, 4, 5, 6). Brain and visceral organs such as liver, heart, and kidney have high metabolic rates in the postabsorptive state, whereas adipose and skeletal muscle tissues have relatively low metabolic rates. Specifically, organs such as liver, brain, kidney, and heart account for only approximately 5% of total body weight (6–7% of FFM); in reference male and female, they collectively account for 58–59% of whole body REE (7). If the mass of one or more high-metabolic-rate organs were to decrease in greater proportion than the mass of low-metabolic-rate organs, REE normalized for FFM would be lower, although the energy flux (kilocalories per kilogram per day) of each organ remained unchanged. Therefore, in order for FFM-adjusted REE to provide evidence for reduced oxygen flux, data must be presented showing that that the proportion of FFM represented by each organ/tissue/fluid is identical in DR and control animals.

The authors do not present or cite such evidence, and the proposition that all organs comprising FFM are changed in a constant proportion after DR is unlikely to be true. A number of animal studies (8, 9, 10, 11, 12) have reported that weight change is accompanied by disproportionate changes in the size of various organs. More recently, Mayer et al. (13) reported preliminary data that organs are reduced disproportionately in patients with anorexia nervosa compared with controls.

It is unfortunate that in this otherwise excellent study and discussion that the heterogeneity of FFM and its bearing on the oxidative flux hypothesis of DR and aging was ignored. Future investigations should consider the in vivo measurements of individual organs and tissues (14, 15) and, where possible, the measurement of tissue specific metabolic rates.

Received February 28, 2003.

References

  1. Blanc S, Schoeller D, Kemnitz J, Weindruch R, Colman R, Newton W, Wink K, Baum S, Ramsey J 2003 Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction. J Clin Endocrinol Metab 88:16–23[Abstract/Free Full Text]
  2. Poehlman ET 2003 Editorial: reduced metabolic rate after caloric restriction—Can we agree on how to normalize the data? J Clin Endocrinol Metab 88:14–15[Free Full Text]
  3. Grande F 1961 Nutrition and energy balance in body composition studies. In: Brozek J, Henschel A, eds. Techniques for measuring body composition. Washington, DC: National Academy of Sciences, National Research Council; 168–188
  4. Holliday MA 1971 Metabolic rate and organ size during growth from infancy to maturity and during late gestation and early infancy. Pediatrics 47:169–179[Abstract]
  5. Holliday MA, Potter D, Jarrah A, Bearg S 1967 The relation of metabolic rate to body weight and organ size. Pediatr Res 1:185–195[Medline]
  6. Elia M 1992 Organ and tissue contribution to metabolic rate. In: Kinney JM, ed. Energy metabolism: tissue determinants and cellular corollaries. New York: Raven Press Ltd.; 61–77
  7. Snyder WS, Cook MJ, et al. 1975 Report of the task group on reference men. International Commission on Radiological Protection No. 23. Oxford, UK: Pergamon Press
  8. Weindruch R, Sohal RS 1997 Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. N Engl J Med 337:986–994[Free Full Text]
  9. Weindruch R, Walford RL 1988 The retardation of aging and disease by dietary restriction. Springfield, IL: CC Thomas
  10. Konarzewski M, Gavin A, McDevitt R, Wallis IR 2000 Metabolic and organ mass responses to selection for high growth rates in the domestic chicken. Physiol Biochem Zool 73:237–248[CrossRef][Medline]
  11. Rompala RE, Johnson DE, Rumpler WV, Phetteplace HW, Specht SM, Parker CF 1991 Energy utilization and organ mass of Targhee sheep selected for rate and efficiency of gain and receiving high and low planes of nutrition. J Anim Sci 1760–1765
  12. Heymsfield SB, McManus C, Stevens V, Smith J 1982 Muscle mass: reliable indicator of protein-energy malnutrition severity and outcome. Am J Clin Nutr 35:1192–1199[Medline]
  13. Mayer L, Walsh BT, Gallagher D, Heymsfield S, Killory E Vital organ sizes in anorexia nervosa. International Conference on Eating Disorders, Boston, MA, 2000, p 108 (Abstract 353)
  14. Gallagher D, Belmonte D, Deurenberg P, Wang Z, Krasnow N, Pi-Sunyer FX, Heymsfield SB 1998 Organ tissue mass measurement allows modeling of resting energy expenditure and metabolically active tissue mass. Am J Physiol 275:E249–E258
  15. Gallagher D, Allen A, Wang Z, Heymsfield SB, Krasnow N 2000 Smaller organ-tissue mass in elderly fails to explain lower resting metabolic rate. Ann NY Acad Sci 904:449–455[Abstract/Free Full Text]




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