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Nature 279, 322 - 323 (24 May 1979); doi:10.1038/279322a0

Reduced thermogenesis in obesity

R. T. JUNG, P. S. SHETTY, W. P. T. JAMES*, M. A. BARRAND & B. A. CALLINGHAM

Medical Research Council, Dunn Clinical Nutrition Centre, Addenbrooke's Hospital, Cambridge
*To whom correspondence should be addressed.
Department of Pharmacology, University of Cambridge, Cambridge, UK

IT is often claimed that there are obese patients who find it difficult to maintain a normal body weight because they have such low energy requirements that even normal intakes of energy result in weight gain and obesity. Studies of both children1 and adults2 show that there can be a twofold difference in energy intake between individuals despite apparently similar patterns of physical activity. An individual variability in the capacity to dissipate heat by metabolic changes has therefore been suggested3 but no physiological basis for the differences in thermogenesis has yet been established. In genetically obese ob/ob mouse there are two components involved in the deposition of excess body fat: hyperphagia and increased metabolic efficiency4,5. Metabolic efficiency is the major factor responsible for obesity when the animals are kept at 20 °C so these animals provide a model study of the link between metabolic rate and obesity. Pre-obese and obese ob/ob animals have an abnormality of thermoregulatory thermogenesis with a reduced thermogenic response to cooling6. A defect in non-shivering thermogenesis can be confirmed by monitoring the thermogenic response to maximum doses of nor adrenaline: the ob/ob mouse has only half the response of its lean littermate. The abnormal thermoregulatory thermogenesis quantitatively accounts for most of the metabolic efficiency of the obese animals as pair feeding at thermoneutrality rather than at 23 °C reduces the excess fat deposited by 65%7. We report here that obese adults with a family history of obesity have a reduced metabolic response to noradrenaline infusion compared with thin adults. As the reduced non-shivering thermogenesis is also found in subjects with familial obesity who remain at normal weight by persistent dieting, the defect in non-shivering thermogenesis appears to be constitutional and not a secondary consequence of obesity.

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