Thermoregulation in genetically obese rodents: the relationship to metabolic efficiency

  • P. Trayhurn
  • P. L. Thurlby
  • C. J. H. Woodward
  • W. P. T. James

Summary

  1. (1)

    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.

     
  2. (2)

    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.

     
  3. (3)

    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.

     
  4. (4)

    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.

     
  5. (5)

    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.

     
  6. (6)

    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.

     
  7. (7)

    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.

     

Keywords

Obesity Adenosine Noradrenaline Catecholamine Zucker 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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
  2. Bray, G. A. and York, D. A. (1971). Genetically transmitted obesity in rodents. Physiol. Rev., 51, 598–646Google Scholar
  3. Chlouverakis, C. (1970). Induction of obesity in obese-hyperglycemic mice on normal food intake. Experientia, 26, 1262–1263CrossRefGoogle Scholar
  4. Cox, J. E. and Powley, T. L. (1977). Development of obesity in diabetic mice pair-fed with lean siblings. J. Comp. Physiol. Psychol., 91, 347–358CrossRefGoogle Scholar
  5. 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
  6. 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
  7. Herberg, L. and Coleman, D. L. (1977). Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism, 26, 59–99CrossRefGoogle Scholar
  8. James, W. P. T. and Trayhurn, P. (1976). An integrated view of the metabolic and genetic basis for obesity. Lancet, ii, 770–773Google Scholar
  9. Jansky, L. (1973). Non-shivering thermogenesis and its thermoregulatory significance. Biol. Rev., 48, 85–132CrossRefGoogle Scholar
  10. Joosten, H. F. P. and van der Kroon, P. H. W. (1974). Role of the thyroid in the development of the obese-hyperglycemic syndrome in mice (oblob). Metabolism, 23, 425–436CrossRefGoogle Scholar
  11. 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
  12. 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
  13. Miller, D. S. and Mumford, P. (1966). Obesity: physical activity and nutrition. Proc. Nutr. Soc., 25, 100–107CrossRefGoogle Scholar
  14. 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
  15. Pullar, J. D. and Webster, A. J. F. (1974). Heat loss and energy retention during growth in congenitally obese and lean rats. Br. J. Nutr., 31, 377–392CrossRefGoogle Scholar
  16. Pullar, J. D. and Webster, A. J. F. (1977). The energy cost of fat and protein deposition in the rat. Br. J. Nutr., 37, 355–363CrossRefGoogle Scholar
  17. Thurlby, P. L. and Trayhurn, P. (1978). The development of obesity in preweanling ob/ob mice. Br. J. Nutr., 39, 391–396CrossRefGoogle Scholar
  18. Thurlby, P. L., Trayhurn, P. and James, W. P. T. (1978) An explanation for the elevated efficiency of the genetically obese (ob/ob) mouse. Proc. Nutr. Soc., 37, 55ACrossRefGoogle Scholar
  19. Trayhurn, P. and James, W. P. T. (1978). Thermoregulation and non-shivering thermogenesis in the genetically obese (ob/ob) mouse. Pflügers Arch. Eur. J. PhysioL, 373, 189–193CrossRefGoogle Scholar
  20. 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
  21. Trayhurn, P., Thurlby, P. L. and James. W. P. T. (1977). Thermogenic defect in pre-obese ob/ob mice. Nature, 266, 60–62CrossRefGoogle Scholar
  22. 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
  23. Wise, P. H. (1977a). Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): oxygen consumption and temperature regulation. Aust. J. Exp. BioL Med. Sci., 55, 463–473CrossRefGoogle Scholar
  24. Wise, P. H. (1977b). Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): cold tolerance, blood glucose and food consumption responses to environmental heat. Aust. J. Exp. BioL Med. Sci., 55, 475–484CrossRefGoogle Scholar
  25. 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
  26. Yen, T. T. T., Fuller, R. W. and Pearson, D. V. (1974). The response of ‘obese’ (ob/ob) and ‘diabetic’ (db/db) mice to treatments that influence body temperature. Comp. Biochem. Physiol., 49A, 377–385CrossRefGoogle Scholar
  27. York, D. A., Bray, G. A. and Yukimura, Y. (1978). An enzymatic defect in the obese (ob/ob) mouse: loss of the thyroid-induced sodium-potassium dependent adenosinetriphosphatase. Proc. Nat. Acad. Sci. USA, 75, 477–481CrossRefGoogle Scholar
  28. York, D. A., Hershman, J. M., Utiger, R. D. and Bray, G. A. (1972). Thyrotropin secretion in genetically obese rats. Endocrinology, 90, 67–72CrossRefGoogle Scholar
  29. Zucker, L. M. (1975). Efficiency of energy utilization by the Zucker hereditarily obese rat ‘fatty’. Proc. Soc. Exp. Biol. Med., 148, 498–500CrossRefGoogle Scholar

Copyright information

© The Medical Research Council 1979

Authors and Affiliations

  • P. Trayhurn
    • 1
  • P. L. Thurlby
    • 1
  • C. J. H. Woodward
    • 1
  • W. P. T. James
    • 1
  1. 1.Dunn Nutrition UnitUniversity of Cambridge and Medical Research CouncilCambridgeUK

Personalised recommendations