Recently models have attempted to integrate the functional relationships of fat mass (FM) and fat-free mass (FFM) with the control of human energy intake (EI). Cross-sectional evidence suggests that at or close to EB, FFM is positively related to hunger and EI, whereas FM either shows a weak negative or no association with ad libitum EI. Further analysis suggests that the effects of FFM and FM on EI may be mediated by resting metabolic rate (RMR). These studies suggest that energy turnover is associated with EI and the largest determinant of energy requirements in most humans is FFM. During chronic positive EBs both FM and FFM expand (but disproportionately so), increasing energy demands. There is little evidence that an expanding FM exerts strong negative feedback on longer term EI. However, during chronic negative EBs FM, FFM and RMR all decrease but appetite increases. Some studies suggest that proportionate loss of FFM during weight loss predicts subsequent weight regain. Taken together these lines of evidence suggest that changes in the size and functional integrity of FFM may influence appetite and EI. Increases in FFM associated with either weight gain or high levels of exercise may ‘pull’ EI upwards but energy deficits that decrease FFM may exert a distinct drive on appetite. The current paper discusses how FM and FFM relationships influence appetite regulation, and how size, structure and functional integrity of FFM may drive EI in humans (i) at EB (ii) during positive EB and (iii) during negative EB.
At or close to EB, FFM is positively associated with EI, whereas FM is either not associated or weakly negatively associated with ad libitum EI.
Associations between FFM, FM and EI are mediated by RMR, suggesting that basal energy turnover may represent an indirect, tonic mechanism that relates energetic demands to EI.
There is little evidence that expanding FM exerts strong negative feedback on EI, but increased FFM associated with weight gain may ‘pull’ EI upwards.
During energy deficits or when growth is retarded, there may be an ‘active’ drive exerted by FFM on EI when FFM is in deficit and its functional integrity is threatened.
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Blaxter K. Energy metabolism in animals and man. Cambridge: Cambridge University Press; 1989.
Mayer J. Regulation of energy intake and the body weight: the glucostatic theory and the lipostatic hypothesis. Ann N Y Acad Sci. 1955;63:15–43.
James WPT. From SDA to DIT to TEF. In: Kinney JM, Tucker HN, editors. Energy matabolism: tissue determinants and cellular corrolaries. New York: Raven Press; 1992; pp. 163–86.
Hall KD. Predicting metabolic adaptation, body weight change, and energy intake in humans. Am J Physiol Endocrinol Metab. 2010;298:449–66.
Newsholme EA. Sounding board. A possible metabolic basis for the control of body weight. N Engl J Med. 1980;302:400–5.
Rothwell NJ, Stock MJ. Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour. Clin Sci. 1983;64:19–23.
Flatt JP. The difference in the storage capacities for carbohydrate and for fat, and its implications in the regulation of body weight. Ann N Y Acad Sci. 1987;499:104–23.
Stubbs J, Ferres S, Horgan G. Energy density of foods: effects on energy intake. Crit Rev Food Sci Nutr. 2000;40:481–515.
Wurtman RJ, Wurtman JJ. Do carbohydrates affect food intake via neurotransmitter activity? Appetite. 1988;11(Suppl 1):42–47.
Le Magnen J. Hunger. Cambridge, United Kingdom: Cambridge University Press; 1985.
Spitzer L, Rodin J. Human eating behaviour: a critical review of studies in normal weight and overweight individuals. Appetite. 1981;2:293–329.
Schwartz MW, Woods SC, Seeley RJ, Barsh GS, Baskin DG, Leibel RL. Is the energy homeostasis system inherently biased toward weight gain? Diabetes. 2003;52:232–8.
Keesey RE, Powley TL. Body energy homeostasis. Appetite. 2008;51:442–5.
Hopkins M, Finlayson G, Duarte C, Whybrow S, Ritz P, Horgan GW, et al. Modelling the associations between fat-free mass, resting metabolic rate and energy intake in the context of total energy balance. Int J Obes. 2016;40:312–8.
Blundell JE, Caudwell P, Gibbons C, Hopkins M, Naslund E, King N, et al. Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation. Dis Model Mech. 2012;5:608–13.
Muller MJ, Baracos V, Bosy-Westphal A, Dulloo AG, Eckel J, Fearon KC, et al. Functional body composition and related aspects in research on obesity and cachexia: report on the 12th Stock Conference held on 6 and 7 September 2013 in Hamburg, Germany. Obes Rev. 2014;15:640–56.
Muller MJ, Bosy-Westphal A, Later W, Haas V, Heller M. Functional body composition: Insights into the regulation of energy metabolism and some clinical applications. Eur J Clin Nutr. 2009;63:1045–56.
Ravussin E, Burnand B, Schutz Y, Jequier E. Twenty-four-hour energy expenditure and resting metabolic rate in obese, moderately obese, and control subjects. Am J Clin Nutr. 1982;35:566–73.
Widdowson EM, Mc CR. Individual dietary surveys. Proc Nutr Soc. 1945;3:110–6.
Prentice AM, Black AE, Murgatroyd PR, Goldberg G, Coward WA. Metabolism or appetite: questions of energy balance with particular reference to obesity. J Human Nutr Diet. 1989;2:95–104.
Jequier E. Calorie balance versus nutrient balance. In: Kinney JM, Tucker HN, editors. Energy metabolism: tissue determinants and cellular corollaries. New York: Raven Press; 1992.
Forbes GB. Lean body mass-body fat inter-relationships in humans. Nutr Rev. 1987;45:225–31.
Forbes GB. Body fat content influences the body composition response to nutrition and exercise. Ann N Y Acad Sci. 2000;904:359–65.
Weinsier RL, Bracco D, Schutz Y. Predicted effects of small decreases in energy expenditure on weight gain in adult women. Int J Obes Relat Metab Disord. 1993;17:693–700.
Deriaz O, Tremblay A, Bouchard C. Non linear weight gain with long term overfeeding in man. Obes Res. 1993;1:179–85.
Diaz EO, Prentice AM, Goldberg GR, Murgatroyd PR, Coward WA. Metabolic response to experimental overfeeding in lean and overweight healthy volunteers. Am J Clin Nutr. 1992;56:641–55.
Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332:621–8.
Webb P, Annis JF. Adaptation to overeating in lean and overweight men and women. Hum Nutr Clin Nutr. 1983;37:117–31.
Joosen AM, Westerterp KR. Energy expenditure during overfeeding. Nutr Metab. 2006;3:25.
Hall KD. Body fat and fat-free mass inter-relationships: Forbes’s theory revisited. Br J Nutr. 2007;97:1059–63.
Hall KD. Modeling metabolic adaptations and energy regulation in humans. Annu Rev Nutr. 2012;32:35–54.
Martin CK, Heilbronn LK, de Jonge L, DeLany JP, Volaufova J, Anton SD, et al. Effect of calorie restriction on resting metabolic rate and spontaneous physical activity. Obesity. 2007;15:2964–73.
Schwartz A, Kuk JL, Lamothe G, Doucet E. Greater than predicted decrease in resting energy expenditure and weight loss: results from a systematic review. Obesity. 2012;20:2307–10.
Weinsier RL, Nagy TR, Hunter GR, Darnell BE, Hensrud DD, Weiss HL. Do adaptive changes in metabolic rate favor weight regain in weight-reduced individuals? An examination of the set-point theory. Am J Clin Nutr. 2000;72:1088–94.
Westerterp KR. Metabolic adaptations to over—and underfeeding—still a matter of debate? Eur J Clin Nutr. 2013;67:443–5.
Polidori D, Sanghvi A, Seeley RJ, Hall KD. How strongly does appetite counter weight loss? Quantification of the feedback control of human energy intake. Obesity. 2016;24:2289–95.
Stubbs RJ, Elia M. Macronutrients and appetite control with implications for the nutritional management of the malnourished. Clin Nutr. 2001;20:129–39.
Prentice AM, Poppitt SD. Importance of energy density and macronutrients in the regulation of energy intake. Int J Obes Relat Metab Disord. 1996;20(Suppl 2):S18–23.
Stubbs RJ. Nutrition Society Medal Lecture. Appetite, feeding behaviour and energy balance in human subjects. Proc Nutr Soc. 1998;57:341–56.
Elia M, Stubbs RJ, Henry CJK. Differences in fat, carbohydrate, and protein metabolism between lean and obese subjects undergoing total starvation. Obes Res. 1999;7:597–604.
Forbes GB. The companionship of lean and fat. Basic Life Sci. 1993;60:1–14.
de Onis M, Monteiro C, Akré J, Clugston G. The worldwide magnitude of protein–energy malnutrition: an overview from the WHO Global Database on Child Growth. Bull World Health Organ. 1993;71:703–12.
Uauy R, Alvear J. Effects of protein–energy interactions on growth. In: Schurch B, Scrimshaw NS, editors. Protein–energy interactions. Lausanne, Switzerland: IDECG; 1992. pp. 151–82.
Garza C, Motil KJ. Protein–energy relationships in pregnancy and lactation. In: Scrimshaw NS, Schurch B, editors. Protein–energy interactions. Lausanne, Switzerland: IDECG; 1992.
Webster AJ. Energy partitioning, tissue growth and appetite control. Proc Nutr Soc. 1993;52:69–76.
Dulloo AG. Collateral fattening: When a deficit in lean body mass drives overeating. Obesity. 2017;25:277–9.
Dulloo AG, Jacquet J, Girardier L. Poststarvation hyperphagia and body fat overshooting in humans: a role for feedback signals from lean and fat tissues. Am J Clin Nutr. 1997;65:717–23.
Dulloo AG, Jacquet J, Miles-Chan JL, Schutz Y. Passive and active roles of fat-free mass in the control of energy intake and body composition regulation. Eur J Clin Nutr. 2017;71:353–7.
Dulloo AG, Jacquet J, Montani JP, Schutz Y. How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obes Rev. 2015;16(Suppl 1):25–35.
Dulloo AG, Montani JP. Pathways from dieting to weight regain, to obesity and to the metabolic syndrome: an overview. Obes Rev. 2015;16(Suppl 1):1–6.
Elia M. Effect of starvation and very low calorie diets on protein–energy inter-relationships and nutrtional needs. In: Scrimshaw NS, Schurch B, editors. Protein–energy interactions. Lausanne, Switzerland: IDECG; 1992.
Scrimshaw NS, Bistrian BR, Brunser O, Elia M, Jackson AA, Jiang JM, et al. Effects of disease on desirable protein/energy ratios. In: Scrimshaw NS, Schürch B, editors. Protein–energy interactions. Lausanne, Switzerland: IDECG; 1992. pp. 385–98.
Keys A, Brozek J, Henschel A, Mickelsen O, Taylor HL. The biology of human starvation. Oxford: University of Minnesota Press; 1950.
Millward DJ. A protein-stat mechanism for regulation of growth and maintenance of the lean body mass. Nutr Res Rev. 1995;8:93–120.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homolog. Nature. 1994;372:425–32.
Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc B. 1953;140:578–92.
Jequier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci. 2002;967:379–88.
Morton G, Cummings D, Baskin D, Barsh G, Schwartz M. Central nervous system control of food intake and body weight. Nature. 2006;443:289–95.
Woods SC, Ramsay DS. Food intake, metabolism and homeostasis. Physiol Behav. 2011;104:4–7.
Blundell J, Caudwell P, Gibbons C, Hopkins M, Naslund E, King N, et al. Body composition and appetite: fat-free mass (but not fat-mass or BMI) is positively associated with self-determined meal size and daily energy intake in humans. Br J Nutr. 2012;107:445–59.
Blundell JE, Finlayson G, Gibbons C, Caudwell P, Hopkins M. The biology of appetite control: do resting metabolic rate and fat-free mass drive energy intake? Physiol Behav. 2015;152(Pt B):473–8.
Lissner L, Habicht J-P, Strupp BJ, Levitsky D, Haas JD, Roe D. Body composition and energy intake: do overweight women overeat and underreport? Am J Clin Nutr. 1989;49:320–5.
Weise CM, Hohenadel MG, Krakoff J, Votruba SB. Body composition and energy expenditure predict ad libitum food and macronutrient intake in humans. Int J Obes. 2014;38:243–51.
Piaggi P, Thearle MS, Krakoff J, Votruba SB. Higher daily energy expenditure and respiratory quotient, rather than fat-free mass, independently determine greater ad libitum overeating. J Clin Endocrinol Metab. 2015;100:3011–20.
Cameron JD, Sigal RJ, Kenny GP, Alberga AS, Prud’homme D, Phillips P, et al. Body composition and energy intake - skeletal muscle mass is the strongest predictor of food intake in obese adolescents: The HEARTY trial. Appl Physiol Nutr Metab. 2016;41:611–7.
Cugini P, Salandri A, Cilli M, Ceccotti P, Di Marzo A, Rodio A, et al. Daily hunger sensation and body composition: I. Their relationships in clinically healthy subjects. Eat Weight Disord. 1998;3:168–72.
Hopkins M, Blundell JE. Energy balance, body composition, sedentariness and appetite regulation: pathways to obesity. Clin Sci. 2016;130:1615–28.
Prentice AM, Black AE, Coward WA, Davies HL, Goldberg GR, Murgatroyd PR, et al. High levels of energy expenditure in obese women. Br Med J. 1986;292:983–7.
Elia M. Organ and tissue contribution to metabolic rate. In: Kinney JM, HNT, editors. Energy metabolism: tissue determinants and cellular corrolaries. New York: Raven Press; 1992; pp. 61–80.
Stubbs RJ, Tolkamp BJ. Control of energy balance in relation to energy intake and energy expenditure in animals and man: an ecological perspective. Br J Nutr. 2006;95:657–76.
Forbes GB. Human body composition: growth, ageing, nutrition and activity. New York: Springer Verlag; 1987.
Owen OE, Smalley KJ, Jungas RL. Starvation. Comprehensive physiology. Supplement 21: Handbook of physiology, the endocrine system, the endocrine pancreas and regulation of metabolism. New York: Wiley; 2011; pp. 1199–225.
Blundell JE, Stubbs RJ. Diet composition and the control of food intake in humans. In: Bray GE, Bouchard C, James WPT, editors. Handbook of obesity. New York: Marcel Dekker; 1998; pp. 243–72.
Doucet E, Cameron J. Appetite control after weight loss: what is the role of bloodborne peptides? Appl Physiol Nutr Metab. 2007;32:523–32.
Heymsfield SB, Gonzalez MC, Shen W, Redman L, Thomas D. Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule. Obes Rev. 2014;15:310–21.
Dulloo AG. Regulation of body composition during weight recovery: integrating the control of energy partitioning and thermogenesis. Clin Nutr. 1997;16(Suppl 1):25–35.
Dulloo AG. Human pattern of food intake and fuel-partitioning during weight recovery after starvation: a theory of autoregulation of body composition. Proc Nutr Soc. 1997;56:25–40.
Crujeiras AB, Goyenechea E, Abete I, Lage M, Carreira MC, Martinez JA, et al. Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J Clin Endocrinol Metab. 2010;95:5037–44.
Kotidis EV, Koliakos GG, Baltzopoulos VG, Ioannidis KN, Yovos JG, Papavramidis ST. Serum ghrelin, leptin and adiponectin levels before and after weight loss: comparison of three methods of treatment—a prospective study. Obes Surg. 2006;16:1425–32.
Pardina E, Lopez-Tejero MD, Llamas R, Catalan R, Galard R, Allende H, et al. Ghrelin and apolipoprotein AIV levels show opposite trends to leptin levels during weight loss in morbidly obese patients. Obes Surg. 2009;19:1414–23.
Redman LM, Heilbronn LK, Martin CK, de Jonge L, Williamson DA, Delany JP, et al. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS ONE. 2009;4:e4377.
Hall KD, Chow CC. Estimating the quantitative relation between food energy intake and changes in body weight. Am J Clin Nutr. 2010;91:816–7.
Goldsmith R, Joanisse DR, Gallagher D, Pavlovich K, Shamoon E, Leibel RL, et al. Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects. Am J Physiol Regul Integr Comp Physiol. 2010;298:79–88.
Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr. 2008;88:906–12.
Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365:1597–604.
Vink RG, Roumans NJ, Arkenbosch LA, Mariman EC, van Baak MA. The effect of rate of weight loss on long-term weight regain in adults with overweight andobesity. Obesity. 2016;24:321–7.
Waterlow JC. Protein–energy inter-relationships during rapid growth. In: Scrimshaw NS, Schürch B, editors. Protein–energy interactions. Lausanne, Switzerland: IDECG; 1992. pp. 183–90.
Forbes J. Voluntary food intake and diet selection in farm animals. Wallingford, Oxfordshire: CAB International; 1995. pp. 305–31.
Cripps AW, Williams VJ. The effect of pregnancy and lactation on food intake, gastrointestinal anatomy and the absorptive capacity of the small intestine in the albino rat. Br J Nutr. 1975;33:17–32.
Forsum E, Kabir N, Sadurskis A, Westerterp K. Total energy expenditure of healthy Swedish women during pregnancy and lactation. Am J Clin Nutr. 1992;56:334–42.
Soenen S, Martens EA, Hochstenbach-Waelen A, Lemmens SG, Westerterp-Plantenga MS. Normal protein intake is required for body weight loss and weight maintenance, and elevated protein intake for additional preservation of resting energy expenditure and fat-free mass. J Nutr. 2013;143:591–6.
We are most grateful to Adbul Dulloo, Jennifer Miles-Chan and Yves Schutz for insightful scientific discussions, which have improved this work.
Resource (staff time) for RJS, MH, GSF, JEB and CD was funded by the University of Leeds.
All authors edited the manuscript and approved the final draft.
Conflict of interest
The authors declare that they have no conflict of interest.
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Stubbs, R.J., Hopkins, M., Finlayson, G.S. et al. Potential effects of fat mass and fat-free mass on energy intake in different states of energy balance. Eur J Clin Nutr 72, 698–709 (2018). https://doi.org/10.1038/s41430-018-0146-6
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