Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature.

We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and development of obesity and insulin resistance (Lowell, B. B., S. V. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. Kozak, and J. S. Flier. Nature 366: 740-742, 1994). In adult UCP-DTA mice, we measured food intake and food assimilation, locomotor activity, metabolic rate, and body temperature in comparison to control animals. No differences could be observed in food intake or assimilation and locomotor activity. Weight-specific metabolic rates at temperatures between 20 and 37°C, however, were consistently lower in transgenic mice. Continuous telemetric recording of core body temperature showed that transgenic mice displayed a downshift in body temperature levels of ∼0.9°C. In summary, we provide evidence that attenuated body temperature levels alone can be responsible for development of obesity and that BAT thermogenesis is a major determinant of body temperature levels in rodents.