Opinion
EDITORIAL
Weight Loss Maintenance A Hard Nut to Crack Thomas H. Inge, MD, PhD; Robert M. Siegel, MD; Stavra A. Xanthakos, MD
In 1991, a total of 8 people were sealed for 2 years inside a manmade “Biosphere” consisting of a 3-acre ecologically closed habitat. This crew of 4 men and 4 women voluntarily entered the habitat to learn about the interactions between humans and key ecological systems. However, these scientists Related article page 807 serendipitously experienced a hardship that has actually taught the world a great deal more about basic human physiology than ever expected. In the first growing season after entering the Biosphere, an unplanned crop failure resulted in a relative famine in their ecological bubble. This crop failure resulted in a severe calorie imbalance, with an estimated 1784 daily calories per person for the first 6 months instead of the 2000-calorie allowance that was available after the first growing season. In addition, the physical labor needed to survive within the Biosphere (devoid of most modern conveniences) was enormous. The men and women lost a mean of 21% and 14% of their weight, respectively. The physiological changes measured in response to this caloric deficit were judged as medically favorable. Major reductions in blood pressure and levels of insulin, blood glucose, hemoglobin A1c, uric acid, low-density lipoprotein cholesterol, and triglycerides were found. Their bodies burned fat for energy, and all the while, preserved their levels of albumin, transferrin, iron, and other important micronutrients.1 In addition to the real health benefits produced by hypocaloric intake and hard physical work during 6 months of confinement in a highly structured environment, this experience also revealed other clues that their unconscious was quite aware of the weight loss. The autonomic nervous system appeared to go into conservation mode. Levels of triiodothyronine and thyrotropin decreased. Body temperatures of the crew decreased a mean of 1°C to 2°C below normal and sometimes dipped to less than 35.6°C, a level beyond the calibration confidence of their thermometers. With ad libitum food intake after discharge from the Biosphere, their weights more than completely rebounded, as would be expected for a body attempting to reestablish a prefamine weight or set point. In this issue of JAMA Pediatrics, van der Baan-Slootweg et al2 report results from an obesity treatment trial that examined how a highly structured inpatient environment compares with a similar intervention in an outpatient setting for severely obese children and adolescents. The inpatient treatment program was associated with a greater decrease in body mass index (BMI) z scores at 6 months than the ambulatory treatment program and was associated with significant and 796
beneficial metabolic changes at 6 months. However, after discharge from the inpatient setting, the weight loss gains were gradually lost; 2 years after completion of the intervention, the mean BMI z score was no different than baseline for either group. Thus, although the inpatient treatment program had a short-term advantage over ambulatory treatment, no longterm benefit was found for this more intensive (and presumably more expensive) inpatient program. The authors correctly point out that long-term follow-up studies after interventions for pediatric severe obesity are scarce, and those that have been published typically demonstrate disappointing results, because any BMI reductions that may have been apparent during the intervention usually cannot be maintained. The authors identify difficulties with durable change in behaviors on returning to the home environment and routines as the reason underlying the regain of weight. They discuss the possible usefulness of a familybased, multifaceted chronic disease model to improve durability of the response. Although this hypothesis merits testing, another important rationale for the observed weight regain must also be considered. A fascinating complexity of the human machinery is the ability to adapt and survive under all manner of adverse conditions. In terms of weight loss after caloric restriction, provided ample food is available, BMI rebound is expected. Weight regain has been observed repeatedly after weight loss due to dieting, drug therapy, and, to a lesser extent, surgical weight loss. Weight regain is believed to stem from the fact that body weight in mammals is regulated through complex pathways involving the central nervous system, with abundant input from the periphery. In the periphery, signals emanate from the gastrointestinal tract, pancreas, and adipose tissue.3 These signals are integrated in the hypothalamus and other central nervous system sites to regulate appetite, satiety, food intake, and energy expenditure. Thus, whether in the lean or the obese state, body weight appears to be defended staunchly against acute changes. With an acute voluntary weight loss or weight gain, levels of a number of mediators of energy metabolism are altered in a direction that attempts to reestablish the starting weight. The compensatory changes that occur in response to caloric restriction include marked reductions in resting and nonresting 24-hour energy expenditure,4 documented in the Biosphere as reduced thermogenesis, for example. Appetite and satiety are also powerfully affected by caloric restriction. The biological basis for this effect involves changes in the complex interplay of key satiety mediators that have important roles
JAMA Pediatrics September 2014 Volume 168, Number 9
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 05/31/2015
jamapediatrics.com
Editorial Opinion
regulating food intake, including leptin, cholecystokinin, peptide YY, amylin, pancreatic polypeptide, and glucagonlike peptide-1. In addition, weight loss stimulates ghrelin, an orexigenic hormone that promotes food intake and thus weight regain. Moreover, after dietary interventions, these powerful compensatory mechanisms that promote regain of lost weight are not just transient but may persist for more than a year after weight loss, beyond the start of weight regain.5 This finding is intriguing because it would lend biological credibility to the observation that after dieting, weight is often regained to levels higher than baseline. These findings also call into question the potential usefulness of a multifaceted chronic disease model to improve durability of the response to lifestyle interventions for pediatric obesity. Some component of weight regain may well be hard-wired and not simply due to resumption of old behaviors. Most of the work to elucidate physiological factors that promote weight regain after loss has been performed in r o d e n t m o d e l s o r a d u l t h u m a n s . H o w e v e r, o t h e r investigators6 have reported that severely obese children in the age range of 6 to 9 years enjoy a much better and seemingly more durable response to a weight loss intervention than older children or adolescents (or adults for that matARTICLE INFORMATION Author Affiliations: Department of Surgery, University of Cincinnati, Cincinnati, Ohio (Inge); Department of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (Inge); Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio (Inge, Siegel, Xanthakos); Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (Siegel, Xanthakos). Corresponding Author: Thomas H. Inge, MD, PhD, Department of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229 (thomas.inge@cchmc .org). Published Online: July 14, 2014. doi:10.1001/jamapediatrics.2014.672. Conflict of Interest Disclosures: None reported. REFERENCES 1. Walford RL, Mock D, MacCallum T, Laseter JL. Physiologic changes in humans subjected to severe,
jamapediatrics.com
ter). Perhaps physiological compensations that promote weight regain after initial loss may be less powerful in younger groups than in older individuals. In addition, studies of the physiological impact of Roux-en-Y gastric bypass and sleeve gastrectomy suggest that these metabolic weight loss operations may have long-term durability that is related less to mechanical/anatomical changes and more to changes in appetite and satiety mediators, favoring decreased appetite and enhanced satiety postoperatively. 7,8 Additional studies have suggested that Roux-en-Y gastric bypass also favorably changes the intestinal microbiome9 and may also enhance energy expenditure in rodents.10 If the ultimate goal is to overcome the physiological tendency toward weight regain after obesity treatment, more must be learned about the molecular mediators and how they interact to achieve regulation of body weight. We must continue to define how weight loss interventions, whether dietary, pharmacologic, or surgical, affect or are affected by the BMI set point of an individual. We hope that the future will hold more effective and durable obesity treatment paradigms when weight loss solutions take into account the full complexity of the biological and psychosocial factors that bear on weight loss maintenance.
selective calorie restriction for two years in Biosphere 2: health, aging, and toxicological perspectives. Toxicol Sci. 1999;52(2 suppl):61-65. 2. van der Baan-Slootweg O, Benninga MA, Beelen A, et al. Inpatient treatment of children and adolescents with severe obesity in the Netherlands: a randomized clinical trial [published online July 24, 2014]. JAMA Pediatr. doi:10.1001/jamapediatrics .2014.521. 3. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404(6778):661-671. 4. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332(10):621-628. 5. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604.
7. Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183188. 8. Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2014;2(2):152-164. 9. Liou AP, Paziuk M, Luevano JM Jr, Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178): 178ra141. doi:10.1126/scitranslmed.3005687. 10. Stylopoulos N, Hoppin AG, Kaplan LM. Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity (Silver Spring). 2009;17(10): 1839-1847.
6. Danielsson P, Kowalski J, Ekblom Ö, Marcus C. Response of severely obese children and adolescents to behavioral treatment. Arch Pediatr Adolesc Med. 2012;166(12):1103-1108.
JAMA Pediatrics September 2014 Volume 168, Number 9
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 05/31/2015
797
EDITORIAL
Weight Loss Maintenance A Hard Nut to Crack Thomas H. Inge, MD, PhD; Robert M. Siegel, MD; Stavra A. Xanthakos, MD
In 1991, a total of 8 people were sealed for 2 years inside a manmade “Biosphere” consisting of a 3-acre ecologically closed habitat. This crew of 4 men and 4 women voluntarily entered the habitat to learn about the interactions between humans and key ecological systems. However, these scientists Related article page 807 serendipitously experienced a hardship that has actually taught the world a great deal more about basic human physiology than ever expected. In the first growing season after entering the Biosphere, an unplanned crop failure resulted in a relative famine in their ecological bubble. This crop failure resulted in a severe calorie imbalance, with an estimated 1784 daily calories per person for the first 6 months instead of the 2000-calorie allowance that was available after the first growing season. In addition, the physical labor needed to survive within the Biosphere (devoid of most modern conveniences) was enormous. The men and women lost a mean of 21% and 14% of their weight, respectively. The physiological changes measured in response to this caloric deficit were judged as medically favorable. Major reductions in blood pressure and levels of insulin, blood glucose, hemoglobin A1c, uric acid, low-density lipoprotein cholesterol, and triglycerides were found. Their bodies burned fat for energy, and all the while, preserved their levels of albumin, transferrin, iron, and other important micronutrients.1 In addition to the real health benefits produced by hypocaloric intake and hard physical work during 6 months of confinement in a highly structured environment, this experience also revealed other clues that their unconscious was quite aware of the weight loss. The autonomic nervous system appeared to go into conservation mode. Levels of triiodothyronine and thyrotropin decreased. Body temperatures of the crew decreased a mean of 1°C to 2°C below normal and sometimes dipped to less than 35.6°C, a level beyond the calibration confidence of their thermometers. With ad libitum food intake after discharge from the Biosphere, their weights more than completely rebounded, as would be expected for a body attempting to reestablish a prefamine weight or set point. In this issue of JAMA Pediatrics, van der Baan-Slootweg et al2 report results from an obesity treatment trial that examined how a highly structured inpatient environment compares with a similar intervention in an outpatient setting for severely obese children and adolescents. The inpatient treatment program was associated with a greater decrease in body mass index (BMI) z scores at 6 months than the ambulatory treatment program and was associated with significant and 796
beneficial metabolic changes at 6 months. However, after discharge from the inpatient setting, the weight loss gains were gradually lost; 2 years after completion of the intervention, the mean BMI z score was no different than baseline for either group. Thus, although the inpatient treatment program had a short-term advantage over ambulatory treatment, no longterm benefit was found for this more intensive (and presumably more expensive) inpatient program. The authors correctly point out that long-term follow-up studies after interventions for pediatric severe obesity are scarce, and those that have been published typically demonstrate disappointing results, because any BMI reductions that may have been apparent during the intervention usually cannot be maintained. The authors identify difficulties with durable change in behaviors on returning to the home environment and routines as the reason underlying the regain of weight. They discuss the possible usefulness of a familybased, multifaceted chronic disease model to improve durability of the response. Although this hypothesis merits testing, another important rationale for the observed weight regain must also be considered. A fascinating complexity of the human machinery is the ability to adapt and survive under all manner of adverse conditions. In terms of weight loss after caloric restriction, provided ample food is available, BMI rebound is expected. Weight regain has been observed repeatedly after weight loss due to dieting, drug therapy, and, to a lesser extent, surgical weight loss. Weight regain is believed to stem from the fact that body weight in mammals is regulated through complex pathways involving the central nervous system, with abundant input from the periphery. In the periphery, signals emanate from the gastrointestinal tract, pancreas, and adipose tissue.3 These signals are integrated in the hypothalamus and other central nervous system sites to regulate appetite, satiety, food intake, and energy expenditure. Thus, whether in the lean or the obese state, body weight appears to be defended staunchly against acute changes. With an acute voluntary weight loss or weight gain, levels of a number of mediators of energy metabolism are altered in a direction that attempts to reestablish the starting weight. The compensatory changes that occur in response to caloric restriction include marked reductions in resting and nonresting 24-hour energy expenditure,4 documented in the Biosphere as reduced thermogenesis, for example. Appetite and satiety are also powerfully affected by caloric restriction. The biological basis for this effect involves changes in the complex interplay of key satiety mediators that have important roles
JAMA Pediatrics September 2014 Volume 168, Number 9
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 05/31/2015
jamapediatrics.com
Editorial Opinion
regulating food intake, including leptin, cholecystokinin, peptide YY, amylin, pancreatic polypeptide, and glucagonlike peptide-1. In addition, weight loss stimulates ghrelin, an orexigenic hormone that promotes food intake and thus weight regain. Moreover, after dietary interventions, these powerful compensatory mechanisms that promote regain of lost weight are not just transient but may persist for more than a year after weight loss, beyond the start of weight regain.5 This finding is intriguing because it would lend biological credibility to the observation that after dieting, weight is often regained to levels higher than baseline. These findings also call into question the potential usefulness of a multifaceted chronic disease model to improve durability of the response to lifestyle interventions for pediatric obesity. Some component of weight regain may well be hard-wired and not simply due to resumption of old behaviors. Most of the work to elucidate physiological factors that promote weight regain after loss has been performed in r o d e n t m o d e l s o r a d u l t h u m a n s . H o w e v e r, o t h e r investigators6 have reported that severely obese children in the age range of 6 to 9 years enjoy a much better and seemingly more durable response to a weight loss intervention than older children or adolescents (or adults for that matARTICLE INFORMATION Author Affiliations: Department of Surgery, University of Cincinnati, Cincinnati, Ohio (Inge); Department of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (Inge); Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio (Inge, Siegel, Xanthakos); Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (Siegel, Xanthakos). Corresponding Author: Thomas H. Inge, MD, PhD, Department of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229 (thomas.inge@cchmc .org). Published Online: July 14, 2014. doi:10.1001/jamapediatrics.2014.672. Conflict of Interest Disclosures: None reported. REFERENCES 1. Walford RL, Mock D, MacCallum T, Laseter JL. Physiologic changes in humans subjected to severe,
jamapediatrics.com
ter). Perhaps physiological compensations that promote weight regain after initial loss may be less powerful in younger groups than in older individuals. In addition, studies of the physiological impact of Roux-en-Y gastric bypass and sleeve gastrectomy suggest that these metabolic weight loss operations may have long-term durability that is related less to mechanical/anatomical changes and more to changes in appetite and satiety mediators, favoring decreased appetite and enhanced satiety postoperatively. 7,8 Additional studies have suggested that Roux-en-Y gastric bypass also favorably changes the intestinal microbiome9 and may also enhance energy expenditure in rodents.10 If the ultimate goal is to overcome the physiological tendency toward weight regain after obesity treatment, more must be learned about the molecular mediators and how they interact to achieve regulation of body weight. We must continue to define how weight loss interventions, whether dietary, pharmacologic, or surgical, affect or are affected by the BMI set point of an individual. We hope that the future will hold more effective and durable obesity treatment paradigms when weight loss solutions take into account the full complexity of the biological and psychosocial factors that bear on weight loss maintenance.
selective calorie restriction for two years in Biosphere 2: health, aging, and toxicological perspectives. Toxicol Sci. 1999;52(2 suppl):61-65. 2. van der Baan-Slootweg O, Benninga MA, Beelen A, et al. Inpatient treatment of children and adolescents with severe obesity in the Netherlands: a randomized clinical trial [published online July 24, 2014]. JAMA Pediatr. doi:10.1001/jamapediatrics .2014.521. 3. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404(6778):661-671. 4. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332(10):621-628. 5. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604.
7. Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183188. 8. Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2014;2(2):152-164. 9. Liou AP, Paziuk M, Luevano JM Jr, Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178): 178ra141. doi:10.1126/scitranslmed.3005687. 10. Stylopoulos N, Hoppin AG, Kaplan LM. Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity (Silver Spring). 2009;17(10): 1839-1847.
6. Danielsson P, Kowalski J, Ekblom Ö, Marcus C. Response of severely obese children and adolescents to behavioral treatment. Arch Pediatr Adolesc Med. 2012;166(12):1103-1108.
JAMA Pediatrics September 2014 Volume 168, Number 9
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 05/31/2015
797
