Advertisement

Thermogenic Responses Induced by Nutrients in Man: Their Importance in Energy Balance Regulation

  • Eric Jequier
Part of the Experientia Supplementum book series (EXS, volume 44)

Summary

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.

Keywords

Brown Adipose Tissue Cold Exposure Plasma Noradrenaline Level Energy Dissipative Mechanism Cafeteria Diet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Acheson, K.J., Flatt, J.P. & Jéquier, E. (1982) Glycogen synthesis versus lipogenesis after a 500 gram carbohydrate meal in man. Metabolism 31: 1234–1240.CrossRefGoogle Scholar
  2. Ball, E.G. & Jungas, R.L. (1961) On the action of hormones which accelerate the rate of oxygen consumption and fatty acid release in rat adipose tissue in vitro. Proc. Natl. Acad. Sci. USA 47: 932–941.CrossRefGoogle Scholar
  3. Case, J.E. & Powley, T.L. (1977) Development of obesity in diabetic mice pair-fed with lean siblings. J. Comp. Physiol. Psychol. 91: 347–358.CrossRefGoogle Scholar
  4. 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
  5. DeFronzo, R.A., Jacot, E., Jéquier, E., Maeder, E., Wahren, J. & Felber, J.P. (1981) The effect of insulin on the disposal of intravenous glucose: results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30: 1000–1007.CrossRefGoogle Scholar
  6. 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
  7. Foster, D.O. & Frydman, M.L. (1978) Nonshivering thermogenesis in the rat. II. Measurement of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline. Can. J. Physiol. Pharmacol. 56: 110–122.CrossRefGoogle Scholar
  8. 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
  9. Garrow, J.S. (1978b) Energy balance and obesity in man. Elsevier/North-Holland Biomedical Press, Amsterdam, New York, Oxford, p. 48.Google Scholar
  10. 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
  11. 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
  12. Golay, A., Schutz, Y., Meyer, H.U., Thiébaud, D., Curchod, B., Maeder, E., Felber, J.P. & Jéquier, E. (1982b) Glucose induced thermogenesis in non-diabetic and diabetic obese subjects. Diabetes 31: 1023–1028.CrossRefGoogle Scholar
  13. Goldman, J.K., Bernadis, L.L. & Frohman, L.A. (1977) Food intake in hypothalamic obesity. Am. J. Physiol. 227: 88–91.Google Scholar
  14. 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
  15. Heaton, J.M. (1972) The distribution of brown adipose tissue in the human. J. Anat. 112: 35–39.Google Scholar
  16. Himms-Hagen, J. & Desautels, M. (1978) A mitochondrial defect in brown adipose tissue of obese (ob/ob) mouse: reduced binding of purine nucleotides and a failure to respond to cold by an increase in binding. Biochem. Biophys. Res. Comm. 83: 628–634.CrossRefGoogle Scholar
  17. Ismail-Beigi, F. & Edelman, I.S. (1970). Mechanisms of thyroid calori-genesis: role of active sodium transport. Proc. Natl. Acad. Sci. USA 67: 1071–1078.CrossRefGoogle Scholar
  18. James, W.P.T. & Trayhurn, P. (1976) An integrated view of the metabolic and genetic basis for obesity. Lancet 2: 770–772.CrossRefGoogle Scholar
  19. James, W.P.T., Bailes, J., Davies, H.L. & Dauncey, M.J. (1978) Elevated metabolic rates in obesity. Lancet 1: 1122–1125.CrossRefGoogle Scholar
  20. 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
  21. 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
  22. Jéquier, E., Pittet, Ph. & Gygax, P.H. (1978) Thermic effect of glucose and thermal body insulation in lean and obese subjects: a calorimetric approach. Proc. Nutr. Soc. 37: 45–53.CrossRefGoogle Scholar
  23. Jung, R.T., Shetty, P.S. & James, W.P.T. (1979) Reduced thermogenesis in obesity. Nature (London) 279: 322–323.CrossRefGoogle Scholar
  24. McCarthy, M.G. (1966) Dietary and activity patterns of obese women in Trinidad. J. Am. Diet. Ass. 48: 33–37.Google Scholar
  25. Newsholme, E.A. (1980) A possible basis for the control of body weight. N. Eng. J. Med., 302: 400–405.CrossRefGoogle Scholar
  26. Nicholls, D.G. (1979) Brown adipose tissue mitochondria. Biochim. Biophys. Acta 549: 1–29.CrossRefGoogle Scholar
  27. Novin, D., Wyrwicka, W. & Bray, G. (Ed.) (1976) Hunger: Basic mechanisms and clinical implications. Raven Press, New York, 494 pp.Google Scholar
  28. Perkins, N.M., Rothwell, N.J., Stock, M.J. & Stone, T.W. (1981) Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature (London) 209: 401–402.CrossRefGoogle Scholar
  29. Pittet, Ph., Gygax, P.H. & Jéquier, E. (1974) Thermic effect of glucose and amino acids in man studied by direct and indirect calorimetry. Br. J. Nutr. 31: 343–349.CrossRefGoogle Scholar
  30. 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
  31. Rothwell, N.J. & Stock, M.J. (1979) A role for brown adipose tissue in diet-induced thermogenesis. Nature (London) 281: 31–55.CrossRefGoogle Scholar
  32. Rothwell, N.J. & Stock, M.J. (1980) Similarities between cold and diet-induced thermogenesis in the rat. Can. J. Physiol. Pharmacol. 58: 842–848.CrossRefGoogle Scholar
  33. Rothwell, N.J. & Stock, M.J. (1981a) Influence of noradrenaline on blood flow to brown adipose tissue in rats exhibiting diet-induced thermogenesis. Pflügers Arch. 389: 237–242.CrossRefGoogle Scholar
  34. Rothwell, N.J. & Stock, M.J. (1981b) Regulation of energy balance. Ann. Rev. Nutr. 1: 235–256.CrossRefGoogle Scholar
  35. Rowe, J.W., Young, J.B., Minaker, K.L., Stevens, A.L., Pallotta, J. & Landsberg, L. (1981) Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 30: 219–225.CrossRefGoogle Scholar
  36. 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
  37. 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
  38. Seydoux, J., Rohner-Jeanrenaud, F., Assimacopoulos-Jeannet, F., Jeanrenaud, B. & Girardier, L. (1981) Functional disconnection of brown adipose tissue in hypothalamic obesity in rats. Pflügers Arch. 390: 1–4.CrossRefGoogle Scholar
  39. 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
  40. 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
  41. 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
  42. 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
  43. Thurlby, P.L. & Trayhurn, P. (1979) The rôle of thermoregulatory thermogenesis in the development of obesity in genetically obese (ob/ob) mice pair fed with lean siblings. Br. J. Nutr. 42: 377–385.CrossRefGoogle Scholar
  44. Thurlby, P.L. & Trayhurn, P. (1980) Regional blood flow in genetically obese (ob/ob) mice. Pflügers Arch. 385: 193–201.CrossRefGoogle Scholar
  45. Trayhurn, P., Thurlby, P.L. & James, W.P.T. (1977) Thermogenic defect in pre-obese ob/ob mice. Nature (London) 266: 60–62.CrossRefGoogle Scholar
  46. Welle, S., Lilavivat, U. & Campbell, R.G. (1981) Thermic effect of feeding in man: increased norepinephrine levels following glucose but not protein or fat consumption. Metabolism 30: 953–958.CrossRefGoogle Scholar
  47. Young, J.B. & Landsberg, L. (1977) Stimulation of the sympathetic nervous system during sucrose feeding. Nature (London) 269: 615–617.CrossRefGoogle Scholar
  48. 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
  49. Young, J.B., Rowe, J.W., Pallotta, J.A., Sparrow, D. & Landsberg, L. (1980) Enhanced plasma norepinephrine response to upright posture and oral glucose administration in elderly human subjects. Metabolism 29: 532–539.CrossRefGoogle Scholar
  50. Yousef, M.K. & Chaffer, R.R.J. (1970) Studies on protein-turnover in cold-acclimated rats. Proc. Soc. Exp. Biol. Med. 133: 801–804.CrossRefGoogle Scholar

Copyright information

© Springer Basel AG 1983

Authors and Affiliations

  • Eric Jequier
    • 1
  1. 1.Institute of Physiology, Division of Clinical PhysiologyUniversity of LausanneLausanneSwitzerland

Personalised recommendations