On raising energy expenditure in ob/ob mice.

Jay C. Erickson et al. (1) describe the energy intake and energy expenditure of mutant obese mice (ob/ob) in which the gene for neuropeptide Y (NPY) is disrupted. They conclude that deficiency of NPY in the ob/ob mouse reduces the elevated food intake and increases the low energy expenditure, partially ameliorating the obesity. Another report, by Mary Ann Pelleymounter et al. (2), describes energy intake and energy expenditure of ob/ob mice treated with OB protein or saline. They conclude that treatment with OB protein (leptin) reduces food intake and increases energy expenditure, ameliorating the obesity. In both studies, food intake is presented in units of grams per mouse. Food intake of ob/ob mice is indeed reduced both by disruption of the gene for NPY and by treatment with OB protein. However, data for energy expenditure are expressed as milliliters of oxygen consumed per kilogram of body weight per hour. Why divide energy expenditure by body weight? The ob/ob mouse contains much more metabolically inert body fat than the lean mouse. The NPY2/2 ob/ob mouse contains less body fat than the ob/ob mouse, but still more than the lean mouse. Likewise, the OB-treated ob/ob mouse contains less body fat than the salinetreated ob/ob mouse. If, from the data in the report, resting oxygen consumption is expressed as total milliliters of oxygen consumed per mouse per hour, a different outcome is seen. Total oxygen consumption in ob/ob mice and in NPY2/2 ob/ob mice is similar and in both cases higher than in lean mice. The apparent increase caused by removal of NPY disappears. Likewise, total oxygen consumption in saline-treated ob/obmice and OB-treated ob/ob mice is similar. The apparent increase caused by the OB treatment disappears. In both studies, and quite correctly, energy intake was not expressed in terms of body weight; had it been so expressed, this would have produced the nonsensical result that ob/ ob mice eat much less than lean mice. Energy expenditure should not be expressed in this way either. I suggest that both research groups recalculate their results (1, 2) to express them as total oxygen consumed per mouse per hour and reconsider their conclusions. Jean Himms-Hagen Department of Biochemistry, University of Ottawa, Ottawa, Ontario K1H 8M5 Canada E-mail: [email protected]