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Do adaptive changes in metabolic rate favor weight regain in weight-reduced individuals? An examination of the set-point theory
Open accessAbstract
Background Obese persons generally regain lost weight, suggesting that adaptive metabolic changes favor return to a preset weight.Objective Our objective was to determine whether adaptive changes in resting metabolic rate (RMR) and thyroid hormones occur in weight-reduced persons, predisposing them to long-term weight gain.Design Twenty-four overweight, postmenopausal women were studied at a clinical research center in four 10-d study phases: the overweight state (phase 1, energy balance; phase 2, 3350 kJ/d) and after reduction to a normal-weight state (phase 3, 3350 kJ/d; phase 4, energy balance). Weight-reduced women were matched with 24 never-overweight control subjects. After each study phase, assessments included RMR (by indirect calorimetry), body composition (by hydrostatic weighing), serum triiodothyronine (T(3)), and reverse T(3) (rT(3)). Body weight was measured 4 y later, without intervention.Results Body composition-adjusted RMR and T(3):rT(3) fell during acute (phase 2) and chronic (phase 3) energy restriction (P: < 0.01), but returned to baseline in the normal-weight, energy-balanced state (phase 4; mean weight loss: 12.9 +/- 2.0 kg). RMR among weight-reduced women (4771 +/- 414 kJ/d) was not significantly different from that in control subjects (4955 +/- 414 kJ/d; P: = 0.14), and lower RMR did not predict greater 4-y weight regain (r = 0.27, NS).Conclusions Energy restriction produces a transient hypothyroid-hypometabolic state that normalizes on return to energy-balanced conditions. Failure to establish energy balance after weight loss gives the misleading impression that weight-reduced persons are energy conservative and predisposed to weight regain. Our findings do not provide evidence in support of adaptive metabolic changes as an explanation for the tendency of weight-reduced persons to regain weight.
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“The energy content of weight-loss maintenance diets should take into account the lower resting metabolic rate and decreased energy requirements due to body mass loss during weight loss.79,80”
From Diet in the management of weight loss (2006) · cites this paper as [80]
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“While changes in metabolic efficiency occur during weight loss, these do not fully explain weight regains.5”
From The mind your health project: a randomized controlled trial of an innovative behavioral treatment for obesity (2013) · cites this paper as [5]
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ResultAreta, J. L., Burke, L. M., Camera, D. M., West, D. W. D., Crawshay, S., Moore, D. R., Stellingwerff, T., Phillips, S. M., Hawley, J. A., & Coffey, V. G. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00590.2013 · Cited by 227
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Predicting metabolic adaptation, body weight change, and energy intake in humans
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“ciency occur during weight loss, these do not fully explain weight regains.(5) Thus, fundamentally, the failure of behavior treatments”
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Enhanced metabolic efficiency contributes to weight regain after weight loss in obesity-prone rats
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“In contrast, there are a similar number of studies that have failed to observed such an adaptation in metabolism or suggest that it resolves during weight maintenance and does not contribute to the propensity to regain weight (1, 8, 30, 48, 52, 53, 56).”
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“Adaptive metabolic changes are not an explanation for the tendency to regain weight [207]: although metabolic responses to weight change are highly individual, metabolic adaptations to long-term weight changes are quite small [208].”
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“Such an acute negative energy balance may have led to transient additional suppression of circulating leptin, sympathetic drive, and thyroid function (27,29,34).”
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“The onset of adaptive thermogenesis is rapid and may correspond to altered levels of circulating thyroid hormones or catecholamines (53, 65).”
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“Our observations are consistent with a considerable amount of evidence in both animals (8, 15, 32, 37, 40, 41) and humans (28, 50, 52, 58, 62) that, in response to calorie-restricted weight reduction, there exists a large positive potential energy imbalance with intake-regulated weight maintenance that does not dissip…”
BackgroundResultIdentifying Metabolically Healthy but Obese Individuals in Sedentary Postmenopausal Women
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“24 overweight women (51) VLED until loss of 10 kg and reaching BMI < 25 kg m-2 ⇓ T3 In early phase of energy restriction ⇑ Reverse T3 ⇓ T3/reverse T3 ratio”
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“30,31 Thus, recommendations for bariatric patients include consuming a higher daily intake of lean Collectively, these data and the present fi ndings suggest that slower weight loss may promote more favorable changes in body composition.”
Thyroid hormone levels predict the change in body weight: a prospective study
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“, 2000), an overall decrease in energy expenditures through reduction in metabolic rates (Buonomo andBaile,1991; Yambayamba et al.,1996;Weinsier et al., 2000), and a modification of development and behaviour in birds and mammals (Moberg, 1985; Ortiz et al.”
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Weight Regain Is Related to Decreases in Physical Activity during Weight Loss
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“Likewise, our RMR results confirm other studies that show a decrease in RMR with dietaryinduced weight loss (1,11,32).”
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Metabolic adaptation is an illusion, only present when participants are in negative energy balance
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“Weight stabilization periods Before (4-wk ambulatory run-in period) and after (5-wk final weight stabilization period) the study, participants were asked to maintain their body weight stable (T2 kg) to reduce the acute effects of body weight fluctuations on outcome variables.(23,24) The intermittent diet group was als…”
BackgroundMethodEffects of intentional weight cycling on non-obese young women
Kajioka, T., Tsuzuku, S., Shimokata, H., & Sato, Y. (2002) · Metabolism · doi:10.1053/meta.2002.29976 · Cited by 60
Farias, M. M., Cuevas, A. M., & Rodríguez, F. (2010) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2010.0090 · Cited by 68
“23 It has also been reported that there is a sense of extreme hunger that may accompany weight loss, which, in turn, promotes calorie-dense food intake, further widening the gap between energy output and intake.”
Ashtary‐Larky, D., Daneghian, S., Alipour, M., Rafiei, H., Ghanavati, M., Mohammadpour, R. A., Kooti, W., Ashtary-Larky, P., & Afrisham, R. (2018) · Intern J Endocrinol Metab · doi:10.5812/ijem.55023 · Cited by 64
“(29), found that calorie restriction (800 kcal/d diet) caused significant decreases in RMR, which was independent of changes in body mass.”
BackgroundMetabolic adaptation is not a major barrier to weight-loss maintenance
Martins, C., Gower, B. A., Hill, J. O., & Hunter, G. R. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa086 · Cited by 64
“All the studies reporting no metabolic adaptation at the level of RMR are studies where weight-stable, reduced-obesity individuals were compared with never-obese BMI-matched controls (2, 4, 18, 35) or against a regression model (20).”
Self-citationA Spatial Economic Analysis of Urban Land Use and Obesity*
Plantinga, A. J., & Bernell, S. L. (2005) · Journal of Regional Science · doi:10.1111/j.0022-4146.2005.00380.x · Cited by 58
Byrne, N. M., Wood, R. E., Schutz, Y., & Hills, A. P. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.109 · Cited by 56
“301 Research on both lean and obese cohorts has demonstrated that RMR reduces rapidly when 302 individuals are placed in energy restriction, with the magnitude of the decrease being greater than can 303 be accounted for by tissue loss (16, 34).”
BackgroundInfluentialMild Calorie Restriction Induces Fat Accumulation in Female C57BL/6J Mice
Li, X., Cope, M. B., Johnson, M. S., Smith, D. L., & Nagy, T. R. (2009) · Obesity · doi:10.1038/oby.2009.312 · Cited by 57
“Further, the reduction in energy expenditure is likely to occur only during the period of negative energy balance, and there will be no relative difference after energy balance is re-established after weight loss (8).”
BackgroundInfluentialSelf-citationFood restriction affects energy metabolism in rat liver mitochondria
Dumas, J. (2003) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2003.11.002 · Cited by 56
“In such circumstances, data suggests that a decrease in energy expenditure [1] and an adaptation of energy metabolism occur due to food restriction [16,17].”
BackgroundDouglas, C. C., Lawrence, J. C., Bush, N. C., Oster, R. A., Gower, B. A., & Darnell, B. E. (2007) · Nutrition Research · doi:10.1016/j.nutres.2007.01.016 · Cited by 52
“Energy balance status affects REE, such that a state of negative energy balance decreases REE [22].”
BackgroundSelf-citationAn artificial neural network to predict resting energy expenditure in obesity
Disse, E., Ledoux, S., Betry, C., Caussy, C., Maitrepierre, C., Coupaye, M., Laville, M., & Simon, C. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.07.017 · Cited by 52
Low Resting and Sleeping Energy Expenditure and Fat Use Do Not Contribute to Obesity in Women
Weinsier, R. L., Hunter, G. R., Zuckerman, P. A., & Darnell, B. E. (2003) · Obesity Research · doi:10.1038/oby.2003.129 · Cited by 51
Self-citationConsequences of inadequate food energy and negative energy balance in humans
Kurpad, A. V., Muthayya, S., & Vaz, M. A. P. (2005) · Public Health Nutrition · doi:10.1079/phn2005796 · Cited by 53
“…a decreased thermogenesis) in AED may also be part of a feedback loop, which regulates the fat deposition on acute re-feeding 25,50 , although other underfeeding studies have not observed a similar effect on either the RMR or on subsequent weight gain after an intervening period of 4 years 51 .”
BackgroundIntermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice
Seimon, R. V., Shi, Y., Slack, K., Lee, K., Fernando, H. A., Nguyen, A., Zhang, L., Lin, S., Enriquez, R. F., Lau, J., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0145157 · Cited by 51
Canadian dietitians’ views and practices regarding obesity and weight management
Barr, S. I., Yarker, K., Levy-Milne, R., & Chapman, G. E. (2004) · Journal of Human Nutrition and Dietetics · doi:10.1111/j.1365-277x.2004.00562.x · Cited by 48
The challenges of implementing behaviour changes that lead to sustained weight management
Stubbs, R. J., & Lavin, J. (2013) · Nutrition Bulletin · doi:10.1111/nbu.12002 · Cited by 52
Jeor, S. T. S., Hayman, L. L., Daniels, S. R., Gillman, M. W., Howard, G., Law, C., Lewis, C. E., & Poehlman, É. T. (2004) · Circulation · doi:10.1161/01.cir.0000140092.48032.d2 · Cited by 44
Chhabra, K. H., Adams, J. M., Jones, G. L., Yamashita, M., Schlapschy, M., Skerra, A., Rubinstein, M., & Low, M. J. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.07.012 · Cited by 42
Estimating Resting Energy Expenditure in Obesity
Foster, G. D., & McGuckin, B. G. (2001) · Obesity Research · doi:10.1002/oby.2001.9.s5.367 · Cited by 45
Amamou, T., Normandin, E., Pouliot, J., Dionne, I. J., Brochu, M., & Riesco, E. (2017) · The Journal of nutrition, health and aging · doi:10.1007/s12603-016-0760-8 · Cited by 40
“Furthermore, we used a 4-week weight stabilization period before and after the intervention to minimize the impact of body weight fluctuations on metabolic profile (47).”
Effect of Aerobic Exercise-induced Weight Loss on the Components of Daily Energy Expenditure
Broskey, N. T., Martin, C. K., Burton, J. H., Church, T. S., Ravussin, É., & Redman, L. M. (2021) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002689 · Cited by 45
“inability for weight loss to be maintained long-term (30,31).”
BackgroundResultForman, E. M., Manasse, S. M., Butryn, M. L., Crosby, R. D., Dallal, D. H., & Crochiere, R. J. (2019) · Obesity · doi:10.1002/oby.22412 · Cited by 40
“Acceptancebased behavioral treatment (ABT) is a variant of SBT premised on a model of self-regulation in which a failure to control weight stems from an inability to remain adherent to prescribed dietary intake and physical activity goals in the face of powerful internal (emotions, boredom, cravings, hunger, fatigue)…”
BackgroundRawson, E. S., Nolan, A., Silver, K. D., Shuldiner, A. R., & Poehlman, É. T. (2002) · Metabolism · doi:10.1053/meta.2002.32781 · Cited by 40
Karl, J. P., Roberts, S. B., Schaefer, E. J., Gleason, J. A., Fuss, P., Rasmussen, H., Saltzman, E. J., & Das, S. K. (2015) · Obesity · doi:10.1002/oby.21268 · Cited by 39
“For experimental validity it may be important to have an extended period of energy balance prior to RMR measurements to prevent the influence of acute effects of overeating or undereating (38).”
BackgroundResultPotential Causes of Elevated REE after High-Intensity Exercise
Hunter, G. R., Moellering, D. R., Carter, S. J., Gower, B. A., Bamman, M. M., Hornbuckle, L. M., Plaisance, E. P., & Fisher, G. (2017) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001386 · Cited by 38
“An energy imbalance could contribute to increased REE (49).”
Self-citationVázquez, C., Montagna, C., Alcaraz, F., Balsa, J. A., Zamarrón, I., Arrieta, F., & Botella-Carretero, J. I. (2009) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2009.48 · Cited by 39
“This difficulty in maintaining weight loss, might be due to the complexity and intensity of the mechanisms that are triggered when dieting, affecting energy balance, appetite control and neurohormonal responses (Weinsier et al., 2000; DelParigi et al., 2004).”
BackgroundSmiles, W. J., Areta, J. L., Coffey, V. G., Phillips, S. M., Moore, D. R., Stellingwerff, T., Burke, L. M., Hawley, J. A., & CAMERA, D. M. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00413.2014 · Cited by 39
“Experimental trials were separated by a 9-day washout period based on data demonstrating that the reduction in resting metabolic rate after a 20-day ED can be restored with 10 days of EB (51).”
MethodResting Energy Expenditure and Organ-Tissue Body Composition 5 Years After Bariatric Surgery
Heshka, S., Lemos, T., Astbury, N. M., Widen, E. M., Davidson, L. E., Goodpaster, B. H., DeLany, J. P., Strain, G. W., Pomp, A., Courcoulas, A. P., et al. (2019) · Obesity Surgery · doi:10.1007/s11695-019-04217-4 · Cited by 37
Sainsbury, A., Wood, R. E., Seimon, R. V., Hills, A. P., King, N. A., Gibson, A. A., & Byrne, N. M. (2018) · Obesity Reviews · doi:10.1111/obr.12787 · Cited by 36
“Whereas some studies showed complete or partial attenuation of certain adaptive responses to energy restriction after 10 days (28), 2 weeks (25,56), 4 weeks (23,24,27), 13 weeks (29,57) or 52 weeks (18) of energy balance or a weight maintenance program, other studies showed no attenuation at all even after 42 weeks (2…”
BackgroundMetabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets
Sadowska, J., Gębczyński, A. K., & Konarzewski, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172892 · Cited by 35
Low-maintenance energy requirements of obese dogs after weight loss
German, A. J., Holden, S. L., Mather, N. J., Morris, P., & Biourge, V. C. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114511000584 · Cited by 33
“However, others((7)) have suggested that a transient hypothyroid–hypometabolic state develops during energy restriction, which returns to normal during subsequent weight maintenance.”
BackgroundMethod
Metadata
- Authors
- Weinsier, R. L., Nagy, T. R., Hunter, G. R., Darnell, B. E., Hensrud, D. D., & Weiss, H. L.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Weinsier, Roland L
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 72
- Issue
- 5
- Pages
- 1088-1094
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2140683236
- Cited by
- 208
- References
- 46
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 13 · 2014: 12 · 2013: 6 · 2012: 15
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01dk038491-01a1, 5r01hl032098-03)
- National Heart, Lung, and Blood Institute (HL32098)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-49779, DK38491, R01DK049779)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Keywords
- weight regain, set-point theory, resting metabolic rate, caloric restriction, thyroid hormones, triiodothyronine, reverse T3, postmenopausal women, obesity, energy balance, body composition, hypometabolism
- MeSH terms
- Aged, Basal Metabolism, Body Composition, Energy Intake, Calorimetry, Indirect, Diet, Reducing, Female, Humans, Kinetics, Middle Aged, Models, Biological, Obesity, Triiodothyronine, Triiodothyronine, Reverse, Weight Gain, Weight Loss, Body Mass Index, Postmenopause
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