Thermogenic Responses Induced by Nutrients in Man: Their Importance in Energy Balance Regulation
The regulation of body weight depends upon the control of food intake and the regulation of energy expenditure. In man, the control system for food intake may be overwhelmed by psychological or social influences and the thermogenic response to a variable energy input may play an important role in the energy regulatory system. Energy expenditure can be divided into 3 components: basal metabolic rate, thermogenesis and physical activity. Of these 3 components, thermogenesis, (i.e. the energy expended above the metabolic rate in the resting state) is the most likely candidate to play a role in the regulation of energy expenditure. The two main factors which contribute to thermogenesis, i.e. food intake and cold exposure, elicit diet-induced thermogenesis (DIT) and non-shivering thermogenesis (NST), respectively. It is of interest to study thermogenesis in individuals who present a tendency to gain weight, in order to assess whether the thermogenic responses may be lower in these subjects than in lean controls.
It has recently been shown that DIT consists of two separate components which can be described as “obligatory” and “regulatory” thermogenesis. The former is due to the energy costs of digesting, absorbing and converting the nutrients to their respective storage forms. The latter is an energy dissipative mechanism, mainly studied in animals. There is good experimental evidence showing that brown adipose tissue (BAT) is involved in the adaptive thermogenesis observed in rats fed a varied and palatable “cafeteria” diet. In addition, a thermogenic defect in BAT has been demonstrated in adult as well as young genetically obese animals, and this defect is present not only in adult, but also in young (12 day old) ob/ob mice, i.e. before the development of obesity. Thus, a defective thermogenesis seems to be a cause, rather than a consequence, of obesity in these animals.
In man, the role of thermogenesis in energy balance regulation is not yet understood. Some conflicting results may have arisen from inadequate techniques to measure energy expenditure. In our laboratory, we have developed three different techniques to measure energy expenditure in man, namely direct calorimetry, indirect calorimetry using an open-circuit ventilated hood system, and a respiratory chamber. Data from recent studies on DIT in man support the concept that a defect in thermogenesis may contribute to energy imbalance and weight gain in obese individuals.
We have been undertaking studies in obese subjects in an attempt to assess whether insulin resistance, which frequently occurs in obesity, affects glucose-induced thermogenesis (GIT). In 55 obese individuals studied over 3 hours following a 100 g oral glucose load, GIT was significantly reduced when compared to that of a control group. It is noteworthy that the magnitude of the reduction in GIT was related to the degree of insulin resistance; the more insulin-resistant patients had the lowest GIT. The measured value of GIT in these insulin-resistant patients corresponded well with the “obligatory” thermogenesis of glucose. By contrast, control subjects exhibited a thermogenic response twice as great, suggesting both “obligatory” and “regulatory” components in their GIT. These results suggest that insulin may be required for the full DIT response, and that insulin resistance contributes to blunt the “regulatory” thermogenesis. In this study we have shown that age also contributes to a decrease in GIT. Thus both insulin resistance and age are factors which decrease the thermogenic response to glucose. These thermogenic defects may account, at least partially, for the increasing occurrence of obesity with age, since they favour energy retention and weight gain.
It is not yet established whether the thermogenic responses due to lipid and protein ingestion are solely accounted for by their respective “obligatory” thermogenesis. Studies on protein turnover rates are needed in man to establish whether adaptive modulations of synthesis and breakdown of protein contribute to a variable thermogenesis.
Finally, it is noteworthy that in rats and mice, there are many common features between DIT and NST including increases in metabolic rate, in thermogenic response to noradrenaline and BAT hypertrophy and hyperplasia. Moreover, these features are all defective in genetically obese mice. In human obese female individuals, we have also shown evidence for a deficiency in both DIT and NST. Further studies are needed to establish whether a defective thermogenesis may precede the development of obesity in man, or whether it is a consequence of the increased body fat mass. Our data showing the progressive decline in GIT with increasing insulin resistance in the obese may favour the latter alternative; however, more work is needed to study the obese after weight loss with the possibility of detecting a defective thermogenesis, independent of the weight excess, and which may be genetically determined.
KeywordsBrown Adipose Tissue Cold Exposure Plasma Noradrenaline Level Energy Dissipative Mechanism Cafeteria Diet
Unable to display preview. Download preview PDF.
- Clearly, M.P., Vasselli, J.R. & Greenwood, M.R.C. (1980) Development of obesity in the Zucker obese (fafa) rat in the absence of hyperphagia. Am. J. Physiol. 238: E284–E292.Google Scholar
- Flatt, J.P. (1978) The biochemistry of energy expenditure. In: Recent Advances in Obesity Research: II (Ed. G. Bray). Newman Publishing London, pp. 211–218.Google Scholar
- Garrow, J.S. (1978a) The regulation of energy expenditure in man. In: Recent Advances in Obesity Research: II (Ed. G. Bray). Newman Publishing London, pp. 200–210.Google Scholar
- Garrow, J.S. (1978b) Energy balance and obesity in man. Elsevier/North-Holland Biomedical Press, Amsterdam, New York, Oxford, p. 48.Google Scholar
- Garrow, J.S. (1981) Thermogenesis and obesity in man. In: Recent Advances in Obesity Research: III (Ed. P. Björntorp, M. Cairella & A.N. Howard). J. Libbey, London, pp. 208–215.Google Scholar
- Golay, A., Schutz, Y., Thiébaud, D., Curchod, B., Felber, J.P. & Jéquier, E. (1982a) Influence of insulin resistance on glucose induced thermogenesis in man. Experientia 38: 714.Google Scholar
- Goldman, J.K., Bernadis, L.L. & Frohman, L.A. (1977) Food intake in hypothalamic obesity. Am. J. Physiol. 227: 88–91.Google Scholar
- Halliday, D., Hesp, R., Stalley, S.F., Warwick, P., Altman, D.G. & Garrow, J.S. (1979) Resting metabolic rate, weight, surface area and body composition in obese women. Int. J. Obesity 3: 1–6.Google Scholar
- Heaton, J.M. (1972) The distribution of brown adipose tissue in the human. J. Anat. 112: 35–39.Google Scholar
- Jéquier, E. (1981) Long term measurement of energy expenditure in man: direct or indirect calorimetry? In: Recent Advances in Obesity Research: III (Ed. P. Björntorp, M. Cairella & A.N. Howard). J. Libbey, London, pp. 130–135.Google Scholar
- Jéquier, E., Gygax, P.H., Pittet, P. & Vannotti, A. (1974) Increased thermal body insulation: relationship to the development of obesity. J. Appl. Physiol. 36: 674–678.Google Scholar
- McCarthy, M.G. (1966) Dietary and activity patterns of obese women in Trinidad. J. Am. Diet. Ass. 48: 33–37.Google Scholar
- Novin, D., Wyrwicka, W. & Bray, G. (Ed.) (1976) Hunger: Basic mechanisms and clinical implications. Raven Press, New York, 494 pp.Google Scholar
- Ravussin, E., Burnand, B., Schutz, Y. & Jéquier, E. (1982) Twenty-four-hour energy expenditure and resting metabolic rate in obese, moderately obese, and control subjects. Am. J. Clin. Nutr. 35: 566–573.Google Scholar
- Schutz, Y., Acheson, K., Bessard, T. & Jéquier, E. (1982a) Energy balance during one week carbohydrate overfeeding in man. Int. J. Vitam. Nutr. Res. 52: 208.Google Scholar
- Schutz, Y., Ravussin, E., Diethelm, R. & Jéquier, E. (1982b) Spontaneous physical activity measured by radar in obese and control subjects in a respiration chamber. Int. J. Obesity 6: 23–28.Google Scholar
- Shetty, P.S., Jung, R.T., James, W.P.T., Barrand, M.A. & Callingham, B.A. (1981) Postprandial thermogenesis in obesity. Clin. Sci. 60: 519–525.Google Scholar
- Stefanik, P.A., Heald, F.P. & Mayer, J. (1959) Calorie intake in relation to energy output of obese and non-obese adolescent boys. Am. J. Clin. Nutr. 7: 55–62.Google Scholar
- Thiébaud, D., Schutz, Y., Acheson, K., Jacot, E., DeFronzo, R., Felber, J.P. & Jéquier, E. (1982) Thermogenesis induced by intravenous glucose/insulin infusion in healthy young men. Int. J. Vitam. Nutr. Res. 52: 209.Google Scholar
- Thiébaud, D., Acheson, K., Schutz, Y., Felber, J.P., Golay, A., DeFronzo, R. & Jéquier, E. (1983) Stimulation of thermogenesis in man following combined glucose-long-chain triglyceride infusion. Am. J. Clin. Nutr. 37: 603–611.Google Scholar
- Young, J.B. & Landsberg, L. (1979) Effect of diet and cold exposure on norepinephrine turnover in pancreas and liver. Am. J. Physiol. 236: E524–E533.Google Scholar