Weight-loss maintenance is challenging, and few succeed in the long term. This study aimed to explain how appetite-related hormones, adaptive thermogenesis, perceived hunger and stress influence weight-loss maintenance.
Fifteen adult women (age, 46.3 ± 9.5 years; BMI, 39.4 ± 4.3 kg/m2) participated in a 24-month intervention, which included 3–5 months total diet replacement (825–853 kcal/d). Body weight and composition (Magnetic Resonance Imaging), resting metabolic rate (indirect calorimetry), and fasting plasma concentration of leptin, ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and growth differentiation factor 15 (GDF-15) were measured at baseline and after weight loss, around 6 months. Perceptions relating to weight-loss maintenance were explored using qualitative interviews.
Mean (SD) changes in body weight (−13.8 ± 6.3 kg) and total adipose tissue (−11.5 ± 4.9 kg) were significant (P < 0.001). Weight loss was associated with a significant reduction in resting metabolic rate (−291 ± 226 kcal/day, P < 0.001) and adaptive thermogenesis (−150 ± 162 kcal/day, P = 0.003), reduction in leptin (P < 0.001) and GLP-1 (P = 0.015), an increase in ghrelin (P < 0.001), and no changes in PYY and GDF-15. Weight regain between 6 and 24 months (6.1 ± 6.3 kg, P < 0.05) was negatively correlated with GLP-1 at baseline (r = −0.7, P = 0.003) and after weight loss (r = −0.7, P = 0.005). Participants did not report increased hunger after weight loss, and stress-related/emotional eating was perceived as the main reason for regain.
Weight regain is more likely with lower fasting GLP-1 at baseline and following weight-loss, but psychological aspects of eating behaviour appear as important in attenuating weight-loss maintenance.
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Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–81.
Di Angelantonio E, Bhupathiraju SN, Wormser D, Gao P, Kaptoge S, de Gonzalez AB, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388:776–86.
Fildes A, Charlton J, Rudisill C, Littlejohns P, Prevost AT, Gulliford MC. Probability of an obese person attaining normal body weight: cohort study using electronic health records. Am J Public Health. 2015;105:E54–9.
Avenell A, Broom J, Brown TJ, Poobalan A, Aucott L, Stearns SC, et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technol Assess. 2004;8:1–465.
Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018;391:541–51.
Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001;74:579–84.
Butland B, Jebb S, Kopelman P, McPherson K, Thomas S, Mardell J, et al. Foresight. Tackling obesities: future choices - project report. London: Government Office for Science, 2007.
Greenway FL. Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes. 2015;39:1188–96.
Hall KD, Kahan S. Maintenance of lost weight and long-term management of obesity. Med Clin North Am. 2018;102:183–97.
Lean MEJ, Malkova D. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence? Int J Obes. 2016;40:622–32.
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.
Iepsen EW, Lundgren J, Holst JJ, Madsbad S, Torekov SS. Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36. Eur J Endocrinol. 2016;174:775–84.
Major GC, Doucet E, Trayhurn P, Astrup A, Tremblay A. Clinical significance of adaptive thermogenesis. Int J Obes. 2007;31:204–12.
Mueller MJ, Bosy-Westphal A. Adaptive thermogenesis with weight loss in humans. Obesity 2013;21:218–28.
Rosenbaum M, Leibel RL. Models of energy homeostasis in response to maintenance of reduced body weight. Obesity. 2016;24:1620–9.
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.
Strohacker K, McCaffery JM, MacLean PS, Wing RR. Adaptations of leptin, ghrelin or insulin during weight loss as predictors of weight regain: a review of current literature. Int J Obes. 2014;38:388–96.
Nymo S, Coutinho SR, Eknes PH, Vestbostad I, Rehfeld JF, Truby H, et al. Investigation of the long-term sustainability of changes in appetite after weight loss. Int J Obes. 2018;42:1489–99.
Nymo S, Coutinho SR, Rehfeld JF, Truby H, Kulseng B, Martins C. Physiological predictors of weight regain at 1-year follow-up in weight-reduced adults with obesity. Obes (Silver Spring, Md). 2019;27:925–31.
Fothergill E, Guo JE, Howard L, Kerns JC, Knuth ND, Brychta R, et al. Persistent metabolic adaptation 6 years after “the biggest loser” competition. Obesity. 2016;24:1612–9.
Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. Obesity 1 the global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378:804–14.
Fatima S, Gerasimidis K, Wright C, Tsiountsioura M, Arvanitidou E-L, Malkova D. Response of appetite and potential appetite regulators following intake of high energy nutritional supplements. Appetite. 2015;95:36–43.
Nymo S, Coutinho SR, Jorgensen J, Rehfeld JF, Truby H, Kulseng B, et al. Timeline of changes in appetite during weight loss with a ketogenic diet. Int J Obes. 2017;41:1224–31.
Levitsky DA. The non-regulation of food intake in humans: hope for reversing the epidemic of obesity. Physiol Behav. 2005;86:623–32.
Kwasnicka D, Dombrowski SU, White M, Sniehotta F. Theoretical explanations for maintenance of behaviour change: a systematic review of behaviour theories. Health Psychol Rev. 2016;10:277–96.
MacLean PS, Wing RR, Davidson T, Epstein L, Goodpaster B, Hall KD, et al. NIH working group report: innovative research to improve maintenance of weight loss. Obesity. 2015;23:7–15.
McCombie L, Brosnahan N, Ross H, Bell-Higgs A, Govan L, Lean M. Filling the intervention gap: service evaluation of an intensive nonsurgical weight management programme for severe and complex obesity. J Hum Nutr Dietetics. 2018;32:329–37.
Compher C, Frankenfield D, Keim N, Roth-Yousey L, Evidence Anal Working G. Best practice methods to apply to measurement of resting metabolic rate in adults: a systematic review. J Am Dietetic Assoc. 2006;106:881–903.
Frayn KN. Calculation of substrate oxidation rates invivo from gaseous exchange. J Appl Physiol. 1983;55:628–34.
Miodownik S, Melendez J, Carlon VA, Burda B. Quantitative methanol-burning lung model for validating gas-exchange measurements over wide ranges of FIO2. J Appl Physiol. 1998;84:2177–82.
Lewis J. Analysing qualitative longitudinal research in evaluations. United Kingdom: Cambridge University Press; 2007. p. 545–56.
Sumithran P, Proietto J. The defence of body weight: a physiological basis for weight regain after weight loss. Clin Sci. 2013;124:231–41.
Adam TCM, Jocken J, Westerterp-Plantenga MS. Decreased glucagon-like peptide 1 release after weight loss in overweight/obese subjects. Obes Res. 2005;13:710–6.
de Luis DA, Gonzalez Sagrado M, Conde R, Aller R, Izaola O. Decreased basal levels of glucagon-like peptide-1 after weight loss in obese subjects. Ann Nutr Metab. 2007;51:134–8.
Zhao X, Han Q, Gang X, Lv Y, Liu Y, Sun C, et al. The role of gut hormones in diet-induced weight change: a systematic review. Horm Metab Res. 2017;49:816–25.
le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007;246:780–5.
Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Investig. 1998;101:515–20.
Makaronidis JM, Batterham RL. Obesity, body weight regulation and the brain: insights from fMRI. Br J Radiol. 2018;91:20170910.
Hayes MR, Schmidt HD. GLP-1 influences food and drug reward. Current Opinion in Behavioural. Current Opin Behav Sci 2016;9:66–70.
Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE maintenance randomized study. Int J Obes. 2013;37:1443–51.
Casanova N, Beaulieu K, Finlayson G, Hopkins M. Metabolic adaptations during negative energy balance and their potential impact on appetite and food intake. Proc Nutr Soc. 2019;78:279–89.
Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SEK, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64:1744–54.
Stubbs J, Whybrow S, Teixeira P, Blundell J, Lawton C, Westenhoefer J, et al. Problems in identifying predictors and correlates of weight loss and maintenance: implications for weight control therapies based on behaviour change. Obes Rev. 2011;12:688–708.
Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating Ghrelin levels are decreased in human obesity. Diabetes. 2001;50:707–9.
Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002;87:240–4.
Rosenbaum M, Nicolson M, Hirsch J, Heymsfield SB, Gallagher D, Chu F, et al. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab. 1996;81:3424–7.
Beck EJ, Tapsell LC, Batterham MJ, Tosh SM, Huang X-F. Oat beta-glucan supplementation does not enhance the effectiveness of an energy-restricted diet in overweight women. Br J Nutr. 2010;103:1212–22.
Pfluger PT, Kampe J, Castaneda TR, Vahl T, D’Alessio DA, Kruthaupt T, et al. Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36. J Clin Endocrinol Metab. 2007;92:583–8.
Sloth B, Due A, Larsen TM, Holst JJ, Heding A, Astrup A. The effect of a high-MUFA, low-glycaemic index diet and a low-fat diet on appetite and glucose metabolism during a 6-month weight maintenance period. Br J Nutr. 2009;101:1846–58.
Coutinho SR, Rehfeld JF, Holst JJ, Kulseng R, Martins C. Impact of weight loss achieved through a multidisciplinary intervention on appetite in patients with severe obesity. Am J Physiol-Endocrinol Metab. 2018;315:E91–8.
Dulloo AG, Jacquet J, Montani JP, Schutz Y. Adaptive thermogenesis in human body weight regulation: more of a concept than a measurable entity? Obes Rev. 2012;13:105–21.
Bosy-Westphal A, Braun W, Schautz B, Mueller MJ. Issues in characterizing resting energy expenditure in obesity and after weight loss. Front Physiol. 2013;4:1–9.
Muller MJ, Enderle J, Pourhassan M, Braun W, Eggeling B, Lagerpusch M, et al. Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited. Am J Clin Nutr. 2015;102:807–19.
Holt GM, Owen LJ, Till S, Cheng Y, Grant VA, Harden CJ, et al. Systematic literature review shows that appetite rating does not predict energy intake. Crit Rev Food Sci Nutr. 2017;57:3577–82.
Finch LE, Tomiyama AJ. Comfort eating, psychological stress, and depressive symptoms in young adult women. Appetite. 2015;95:239–44.
Greaves C, Poltawski L, Garside R, Briscoe S. Understanding the challenge of weight loss maintenance: a systematic review and synthesis of qualitative research on weight loss maintenance. Health Psychol Rev. 2017;11:145–63.
Baumeister R, Vohs K. Self-regulation, ego depletion, and motivation. Soc Personal Psychol Compass. 2007;1:115–28.
Zellner DA, Loaiza S, Gonzalez Z, Pita J, Morales J, Pecora D, et al. Food selection changes under stress. Physiol Behav. 2006;87:789–93.
Sainsbury K, Evans EH, Pedersen S, Marques MM, Teixeira PJ, Lahteenmaki L, et al. Attribution of weight regain to emotional reasons amongst European adults with overweight and obesity who regained weight following a weight loss attempt. Eat weight Disord. 2018;24:351–61.
Rosenbaum M, Agurs-Collins T, Bray MS, Hall KD, Hopkins M, Laughlin M, et al. Accumulating data to optimally predict obesity treatment (ADOPT): recommendations from the biological domain. Obesity. 2018;26:S25–34.
Muller MJ, Enderle J, Bosy-Westphal A. Changes in energy expenditure with weight gain and weight loss in humans. Curr Obes Rep. 2016;5:413–23.
Rosenbaum M, Vandenborne K, Goldsmith R, Simoneau JA, Heymsfield S, Joanisse DR, et al. Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects. Am J Physiol-Regulatory Integr Comp Physiol. 2003;285:R183–92.
Dulloo AG, Schutz Y. Adaptive thermogenesis in resistance to obesity therapies: issues in quantifying thrifty energy expenditure phenotypes in humans. Curr Obes Rep. 2015;4:230–40.
We thank all participants for their time and commitment and Cambridge Weight Plan (Northants, UK) for providing meal replacement products.
Conflict of interest
GT and NB have received funding from Cambridge Weight Plan for conference attendance and for other departmental research. NB has shares in Counterweight Ltd, and is a previous employee of Counterweight Ltd. MEJL reports personal fees from Counterweight Ltd, grants and personal fees from Novo Nordisk, personal fees from Novartis, personal fees from Eli Lilly, and non-financial support from Cambridge Weight Plan, outside the submitted work. The other study authors declare no conflict of interest.
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Thom, G., Dombrowski, S.U., Brosnahan, N. et al. The role of appetite-related hormones, adaptive thermogenesis, perceived hunger and stress in long-term weight-loss maintenance: a mixed-methods study. Eur J Clin Nutr 74, 622–632 (2020). https://doi.org/10.1038/s41430-020-0568-9
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