Editorial See corresponding article on page 996.
The battle of the bulge: defense versus offense1,2 Faidon Magkos, Robyn A Tamboli, Naji N Abumrad, and Samuel Klein after weight loss but were limited to BMI values (in kg/m2) above w40 (ie, for people who remained morbidly obese even after surgically induced weight loss). The authors suggest that, despite the differences in magnitude of weight loss and the mechanisms responsible for weight loss among diet and different surgical therapies, the reduced body weight is still governed by a predetermined set point, and they propose a ‘‘threshold shift paradigm’’ for the relation between adiposity signals (particularly leptin) and body weight control. This model posits that the decline in body fatness that occurs with weight loss results in a reduction in neuroendocrine signals that inhibit food intake and increase energy expenditure. When the intensity of these signals falls below a threshold, a sharp and concerted anabolic response is triggered to increase energy intake and to reduce energy expenditure, and thereby halt the loss of body weight and favor weight regain toward baseline. This defensive response is maximal once the threshold is reached, so that greater weight loss does not produce proportionate increases in the anabolic response (4). The authors further propose that chronic increases in adiposity cause a progressive upward shift in the body fat threshold that is defended. The data from the study by Ferrannini et al (5) are consistent with those observed in previous diet and surgery weight-loss studies, which also found that greater initial body weight and BMI predict greater absolute (kg) and relative (% of initial body weight) weight loss and greater final body weight and BMI (6–9). However, a simpler mechanism than the ‘‘threshold theory’’ could explain this relation. In general, daily energy expenditure is directly correlated with BMI, and ‘‘large’’ people require greater energy intake to maintain body mass than do ‘‘small’’ people. Accordingly, the negative energy balance induced by a specific reduced energy intake is greater for large than for small people. It is possible that the range of actual (not prescribed) energy intake (or absorption) of obese people prescribed a hypocaloric diet or who have had bariatric surgery is limited, so that the relatively larger persons will invariably be at a greater negative energy balance and will therefore lose more weight than the relatively smaller 1 From the Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, MO (FM and SK), and the Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN (RAT and NNA). 2 Address correspondence to F Magkos, Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St Louis, MO 63110. E-mail: [email protected]. First published online August 27, 2014; doi: 10.3945/ajcn.114.096529.
Am J Clin Nutr 2014;100:991–2. Printed in USA. Ó 2014 American Society for Nutrition
991
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Obesity is caused by ingesting more calories than expended over a long period of time. The initial positive energy balance expands body mass and endogenous fat stores, which must then be maintained by continued adequate energy intake. Calorie restriction induces a negative energy balance, which results in consumption of endogenous fat stores as fuel to supplement the inadequate energy intake and to meet the metabolic demands of the body. The decrease in body mass (both fat mass and fat-free mass) results in a decrease in daily energy expenditure. At some point, the reduced-energy diet will match the amount of energy expended, which will lead to a cessation of weight loss and a plateau in body weight at a new lower level. Although many obese people are able to lose weight, successful long-term weight loss maintenance is much more difficult to achieve with lifestyle interventions (diet, physical activity, and behavioral therapy) (1), and most patients who have had bariatric surgery also experience some recidivism over time, even when they maintain a substantial weight loss (2). Why is weight loss so hard to maintain? A prominent theory is that a complex neuroendocrine system regulates food intake and energy expenditure to defend a certain individualized set point in body weight (3, 4). When weight loss occurs, these regulatory signals spring into action to move body weight back to its original predetermined value. In this issue of the Journal, Ferrannini et al (5) expand the details of this theory by examining longitudinal data from 1) normal-weight, overweight, and obese participants in the Relation between Insulin Sensitivity and Cardiovascular Disease (RISC) Study (n ¼ 223), who lost weight spontaneously (presumably from intentional reductions in energy intake) during the 3-y study period, and 2) extremely obese patients before and 1 y after Roux-en-Y gastric bypass surgery (n ¼ 71) or biliopancreatic diversion (n ¼ 111). Their results show that despite a nearly 10-fold difference in the amounts of weight loss between groups (5 6 3 kg or w7% of initial body weight in the diet group and 46 6 17 kg or w35% of initial body weight in the surgery group), there was a very strong association between initial BMI and final BMI in the diet group (r ¼ 0.96) and a weaker, albeit still impressive, association between initial BMI and final BMI in the surgery group (r ¼ 0.67). Furthermore, in a subgroup of 110 bariatric surgery patients, serum leptin concentrations were measured and were found to correlate with BMI both before and after weight loss, but the slope of the regression line was significantly flatter after weight loss than before weight loss, so that the same BMI was associated with much lower serum leptin after weight loss than at baseline. However, lower leptin concentrations were not evident across the whole BMI range
992
EDITORIAL
NNA is an official of OR International and a shareholder of Metabolic Technologies Inc. SK is a shareholder of Aspire Bariatrics, Metro Midwest
Biotech, and Human Longevity Inc; serves as a consultant for Aspire Bariatrics; and serves on the scientific advisory boards of Takeda Pharmaceuticals, Danone/Yakult, and NovoNordisk. FM and RAT declared no conflicts of interest.
REFERENCES 1. Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr 2005;82(suppl):222S–5S. 2. Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, Horlick M, Kalarchian MA, King WC, Mitchell JE, et al. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA 2013;310:2416–25. 3. Rosenbaum M, Leibel RL. Adaptive responses to weight loss. In: Kushner RF, Bessesen DH, eds. Treatment of the obese patient. 2nd ed. New York, NY: Springer Science 1 Business Media, 2014:97–111. 4. Leibel RL, Rosenbaum M. Metabolic responses to weight perturbation. In: Cle´ment K, Spiegelman BM, Christen Y, eds. Novel insights into adipose cell functions. Berlin, Germany: Springer-Verlag, 2010. 5. Ferrannini E, Rosenbaum M, Leibel RL. The threshold shift paradigm of obesity: evidence from surgically induced weight loss. Am J Clin Nutr 2014;100:996–1002. 6. Goodpaster BH, Delany JP, Otto AD, Kuller L, Vockley J, South-Paul JE, Thomas SB, Brown J, McTigue K, Hames KC, et al. Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial. JAMA 2010; 304:1795–802. 7. Unick JL, Beavers D, Jakicic JM, Kitabchi AE, Knowler WC, Wadden TA, Wing RR. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial. Diabetes Care 2011;34:2152–7. 8. Dallal RM, Quebbemann BB, Hunt LH, Braitman LE. Analysis of weight loss after bariatric surgery using mixed-effects linear modeling. Obes Surg 2009;19:732–7. 9. Sczepaniak JP, Owens ML, Garner W, Dako F, Masukawa K, Wilson SE. A simpler method for predicting weight loss in the first year after Roux-en-Y gastric bypass. J Obes 2012;2012:195251.
Downloaded from ajcn.nutrition.org by guest on November 15, 2015
persons. Furthermore, given that the range of relative weight loss (as a percentage of initial body weight) in response to diet is much less than in response to surgery [eg, see Figure 1 in Ferrannini et al (5)], one would expect that initial body weight will correlate much better with final body weight after dietinduced rather than after surgery-induced weight loss—which is exactly what Ferrannini et al observed (5). This notion is supported by a recent analysis of data from .1500 patients who had Roux-en-Y gastric bypass surgery (9), which found that variability in the amount of weight loss increased with time after surgery and thereby weakened the relation between initial and final body weight. This observation suggests that maintenance of long-term weight loss is complex and depends on more factors than initial body weight. The threshold model proposed by Ferrannini et al (5) is an elegant theoretical model that fits their data. The mechanisms responsible for ultimate body weight involve a complex interaction between genetic, endocrine, neurologic, psychological, behavioral, developmental, and environmental (eg, lifestyle, food availability and cost, food marketing, medications, occupation, socioeconomic status, and social network) factors. As evidence supporting a neuroendocrine response to weight loss that is involved in the pathogenesis of weight recidivism continues to accumulate, additional research is needed to understand the importance of this adaptive biological response within the context of the myriad of other underlying inherent and acquired factors that led to excessive energy intake and body fat in the first place.
The battle of the bulge: defense versus offense1,2 Faidon Magkos, Robyn A Tamboli, Naji N Abumrad, and Samuel Klein after weight loss but were limited to BMI values (in kg/m2) above w40 (ie, for people who remained morbidly obese even after surgically induced weight loss). The authors suggest that, despite the differences in magnitude of weight loss and the mechanisms responsible for weight loss among diet and different surgical therapies, the reduced body weight is still governed by a predetermined set point, and they propose a ‘‘threshold shift paradigm’’ for the relation between adiposity signals (particularly leptin) and body weight control. This model posits that the decline in body fatness that occurs with weight loss results in a reduction in neuroendocrine signals that inhibit food intake and increase energy expenditure. When the intensity of these signals falls below a threshold, a sharp and concerted anabolic response is triggered to increase energy intake and to reduce energy expenditure, and thereby halt the loss of body weight and favor weight regain toward baseline. This defensive response is maximal once the threshold is reached, so that greater weight loss does not produce proportionate increases in the anabolic response (4). The authors further propose that chronic increases in adiposity cause a progressive upward shift in the body fat threshold that is defended. The data from the study by Ferrannini et al (5) are consistent with those observed in previous diet and surgery weight-loss studies, which also found that greater initial body weight and BMI predict greater absolute (kg) and relative (% of initial body weight) weight loss and greater final body weight and BMI (6–9). However, a simpler mechanism than the ‘‘threshold theory’’ could explain this relation. In general, daily energy expenditure is directly correlated with BMI, and ‘‘large’’ people require greater energy intake to maintain body mass than do ‘‘small’’ people. Accordingly, the negative energy balance induced by a specific reduced energy intake is greater for large than for small people. It is possible that the range of actual (not prescribed) energy intake (or absorption) of obese people prescribed a hypocaloric diet or who have had bariatric surgery is limited, so that the relatively larger persons will invariably be at a greater negative energy balance and will therefore lose more weight than the relatively smaller 1 From the Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, MO (FM and SK), and the Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN (RAT and NNA). 2 Address correspondence to F Magkos, Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St Louis, MO 63110. E-mail: [email protected]. First published online August 27, 2014; doi: 10.3945/ajcn.114.096529.
Am J Clin Nutr 2014;100:991–2. Printed in USA. Ó 2014 American Society for Nutrition
991
Downloaded from ajcn.nutrition.org by guest on November 15, 2015
Obesity is caused by ingesting more calories than expended over a long period of time. The initial positive energy balance expands body mass and endogenous fat stores, which must then be maintained by continued adequate energy intake. Calorie restriction induces a negative energy balance, which results in consumption of endogenous fat stores as fuel to supplement the inadequate energy intake and to meet the metabolic demands of the body. The decrease in body mass (both fat mass and fat-free mass) results in a decrease in daily energy expenditure. At some point, the reduced-energy diet will match the amount of energy expended, which will lead to a cessation of weight loss and a plateau in body weight at a new lower level. Although many obese people are able to lose weight, successful long-term weight loss maintenance is much more difficult to achieve with lifestyle interventions (diet, physical activity, and behavioral therapy) (1), and most patients who have had bariatric surgery also experience some recidivism over time, even when they maintain a substantial weight loss (2). Why is weight loss so hard to maintain? A prominent theory is that a complex neuroendocrine system regulates food intake and energy expenditure to defend a certain individualized set point in body weight (3, 4). When weight loss occurs, these regulatory signals spring into action to move body weight back to its original predetermined value. In this issue of the Journal, Ferrannini et al (5) expand the details of this theory by examining longitudinal data from 1) normal-weight, overweight, and obese participants in the Relation between Insulin Sensitivity and Cardiovascular Disease (RISC) Study (n ¼ 223), who lost weight spontaneously (presumably from intentional reductions in energy intake) during the 3-y study period, and 2) extremely obese patients before and 1 y after Roux-en-Y gastric bypass surgery (n ¼ 71) or biliopancreatic diversion (n ¼ 111). Their results show that despite a nearly 10-fold difference in the amounts of weight loss between groups (5 6 3 kg or w7% of initial body weight in the diet group and 46 6 17 kg or w35% of initial body weight in the surgery group), there was a very strong association between initial BMI and final BMI in the diet group (r ¼ 0.96) and a weaker, albeit still impressive, association between initial BMI and final BMI in the surgery group (r ¼ 0.67). Furthermore, in a subgroup of 110 bariatric surgery patients, serum leptin concentrations were measured and were found to correlate with BMI both before and after weight loss, but the slope of the regression line was significantly flatter after weight loss than before weight loss, so that the same BMI was associated with much lower serum leptin after weight loss than at baseline. However, lower leptin concentrations were not evident across the whole BMI range
992
EDITORIAL
NNA is an official of OR International and a shareholder of Metabolic Technologies Inc. SK is a shareholder of Aspire Bariatrics, Metro Midwest
Biotech, and Human Longevity Inc; serves as a consultant for Aspire Bariatrics; and serves on the scientific advisory boards of Takeda Pharmaceuticals, Danone/Yakult, and NovoNordisk. FM and RAT declared no conflicts of interest.
REFERENCES 1. Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr 2005;82(suppl):222S–5S. 2. Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, Horlick M, Kalarchian MA, King WC, Mitchell JE, et al. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA 2013;310:2416–25. 3. Rosenbaum M, Leibel RL. Adaptive responses to weight loss. In: Kushner RF, Bessesen DH, eds. Treatment of the obese patient. 2nd ed. New York, NY: Springer Science 1 Business Media, 2014:97–111. 4. Leibel RL, Rosenbaum M. Metabolic responses to weight perturbation. In: Cle´ment K, Spiegelman BM, Christen Y, eds. Novel insights into adipose cell functions. Berlin, Germany: Springer-Verlag, 2010. 5. Ferrannini E, Rosenbaum M, Leibel RL. The threshold shift paradigm of obesity: evidence from surgically induced weight loss. Am J Clin Nutr 2014;100:996–1002. 6. Goodpaster BH, Delany JP, Otto AD, Kuller L, Vockley J, South-Paul JE, Thomas SB, Brown J, McTigue K, Hames KC, et al. Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial. JAMA 2010; 304:1795–802. 7. Unick JL, Beavers D, Jakicic JM, Kitabchi AE, Knowler WC, Wadden TA, Wing RR. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial. Diabetes Care 2011;34:2152–7. 8. Dallal RM, Quebbemann BB, Hunt LH, Braitman LE. Analysis of weight loss after bariatric surgery using mixed-effects linear modeling. Obes Surg 2009;19:732–7. 9. Sczepaniak JP, Owens ML, Garner W, Dako F, Masukawa K, Wilson SE. A simpler method for predicting weight loss in the first year after Roux-en-Y gastric bypass. J Obes 2012;2012:195251.
Downloaded from ajcn.nutrition.org by guest on November 15, 2015
persons. Furthermore, given that the range of relative weight loss (as a percentage of initial body weight) in response to diet is much less than in response to surgery [eg, see Figure 1 in Ferrannini et al (5)], one would expect that initial body weight will correlate much better with final body weight after dietinduced rather than after surgery-induced weight loss—which is exactly what Ferrannini et al observed (5). This notion is supported by a recent analysis of data from .1500 patients who had Roux-en-Y gastric bypass surgery (9), which found that variability in the amount of weight loss increased with time after surgery and thereby weakened the relation between initial and final body weight. This observation suggests that maintenance of long-term weight loss is complex and depends on more factors than initial body weight. The threshold model proposed by Ferrannini et al (5) is an elegant theoretical model that fits their data. The mechanisms responsible for ultimate body weight involve a complex interaction between genetic, endocrine, neurologic, psychological, behavioral, developmental, and environmental (eg, lifestyle, food availability and cost, food marketing, medications, occupation, socioeconomic status, and social network) factors. As evidence supporting a neuroendocrine response to weight loss that is involved in the pathogenesis of weight recidivism continues to accumulate, additional research is needed to understand the importance of this adaptive biological response within the context of the myriad of other underlying inherent and acquired factors that led to excessive energy intake and body fat in the first place.
