Thermoregulation in genetically obese rodents: the relationship to metabolic efficiency
The positive energy balance which leads to obesity is due, in several strains of genetically obese rodent, to a combination of hyperphagia and an elevated metabolic efficiency. The significance of differences in efficiency can be illustrated by a pair-feeding experiment with young ob/ob and lean mice, where the gross efficiency of the obese individuals was 2.3 times greater than that of the lean.
The increased gross efficiency of the ob/ob mouse is due to a reduced maintenance requirement, and not to any reduction in the energy cost of growth. At normal environmental temperatures (18-25°C) the major components of the maintenance requirement are the basal metabolic rate and the energy cost of maintaining homeothermy—thermoregulatory thermogenesis.
Adult ob/ob mice rapidly die of hypothermia at 4°C, indicating that they have a major thermoregulatory defect. ob/ob mice as young as 10 days of age also have an impaired ability to respond to ‘cool’ environments. A thermoregulatory defect is therefore detectable very early in the development of the ob/ob mouse, and can be used as a test for the genotype before obesity is apparent visually.
Between 25 and 10°C the adult ob/ob mouse maintains its body temperature some 2°C below that of lean litter mates. The resting metabolic rate of adult lean and obese ob/ob mice is little different at environmental temperatures within, or close to, the thermoneutral zone. However, at temperatures below thermoneutrality the resting metabolic rate of the obese mice per whole animal is 20 per cent less than that of the lean.
At 33°C (thermoneutrality) young lean and obese (ob/ob) mice have similar energy requirements for weight maintenance, but at 23°C the maintenance requirement of the obese is 16 per cent less than that of the lean. Pair-feeding young obese mice to the ad libitum food intake of their lean litter mates at thermoneutrality eliminates two-thirds of the obese animals’ excess energy gain at 23°C.
The nutritional studies support the metabolic rate measurements in showing that the high gross efficiency of the ob/ob mouse is attributable to a reduced energy expenditure on thermoregulatory thermogenesis. We suggest that the primary reason for this reduction is that the ob/ob mouse may have a lower hypothalamic ‘set-point’ for body temperature.
Thermoregulatory differences appear to be a common feature of genetically obese rodents. This suggests that the mechanism by which the ob/ob mouse achieves its high efficiency is a general one.
KeywordsObesity Adenosine Noradrenaline Catecholamine Zucker
Unable to display preview. Download preview PDF.
- Alonso, L. G. and Maren, T. H. (1955). Effect of food restriction on body composition of hereditary obese mice. Am. J. Physiol., 183, 284–290Google Scholar
- Bray, G. A. and York, D. A. (1971). Genetically transmitted obesity in rodents. Physiol. Rev., 51, 598–646Google Scholar
- Davis, T. R. A. and Mayer, J. (1954). Imperfect homeothermia in the hereditary obese-hyperglycemic syndrome of mice. Am. J. Physiol., 177, 222–226Google Scholar
- Deb, S., Martin, R. J. and Hershberger, T. V. (1976). Maintenance requirement and energetic efficiency of lean and obese Zucker rats. J. Nutr., 106, 191–197Google Scholar
- James, W. P. T. and Trayhurn, P. (1976). An integrated view of the metabolic and genetic basis for obesity. Lancet, ii, 770–773Google Scholar
- Kaplan, M. L. and Leveille, G. A. (1974). Core temperature, OZ consumption and early detection of ob/ob genotype in mice. Am. J. Physiol., 227, 912–915Google Scholar
- Lin, P.-Y., Romsos, D. R. and Leveille, G. A. (1977). Food intake, body weight gain, and body composition of the young obese (ob/ob) mouse. J. Nutr., 107, 1715–1723Google Scholar
- Ohtake, M., Bray, G. A. and Azukizawa, M. (1977). Studies on hypothermia and thyroid function in the obese (ob/ob) mouse. Am. J. Physiol., 233, R110 - R115Google Scholar
- Trayhurn, P., Thurlby, P. L. and James, W. P. T. (1976). A defective response to cold in the obese (ob/ob) mouse and the obese Zucker (fa/fa) rat. Proc. Nutr. Soc., 35, 133AGoogle Scholar
- Welton, R. F., Martin, R. J. and Baumgardt, B. R. (1973). Effects of feeding and exercise regimens on adipose tissue glycerokinase activity and body composition of lean and obese mice. J. Nutr., 103, 1212–1219Google Scholar
- Woodward, C. J. H., Trayhurn, P. and James, W. P. T. (1977). Costs of maintenance and growth in genetically obese (ob/ob) mice. Proc. Nutr. Soc., 36, 115AGoogle Scholar