Thermodynamics, Liposuction, and Metabolism
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《新英格兰医药杂志》
The regulation of body weight adheres to the principles of thermodynamics: a positive energy balance causes weight gain, and weight loss occurs when the energy expenditure exceeds intake. More than half the adults in the United States are overweight or obese, and many of these people make an effort, at least intermittently, to lose weight. The results of clinical trials such as the Diabetes Prevention Program provide good evidence that a moderate amount of weight loss plus increased physical activity reduces the likelihood of progression from impaired glucose tolerance to type 2 diabetes mellitus.1 Although the long-term health benefits of weight loss remain to be delineated, the positive effect of weight loss on type 2 diabetes and other obesity-related conditions bolsters the medical perception that weight loss improves health in overweight and obese persons.
It has been argued that a substantial portion of the metabolic benefits that occur in response to weight loss are directly related to the effects of a negative energy balance. Glucose and insulin homeostasis provide robust biologic markers of the effects of interventions in type 2 diabetes. Henry et al. were among the first to observe that hyperglycemia improves rapidly during caloric restriction, outpacing the rate of weight loss.2 Later studies confirmed their observations and revealed that approximately half of the improvement in insulin resistance and glycemic control induced by the loss of 15 percent of total body weight was achieved during the first week in which there was a negative energy balance.3 The actual fat loss is typically quite small during short periods of caloric restriction; weight loss during such periods is achieved largely through the increased excretion of sodium and water, not through the loss of adipose tissue.
These and additional studies suggested that a substantial proportion of the beneficial metabolic effects of weight loss on insulin resistance and hyperglycemia in type 2 diabetes may be more correctly attributed to the effects of a negative energy balance. Similar observations have been made concerning hypertension: much of the decrease in blood pressure occurs fairly rapidly in response to a negative energy balance. Observations in patients undergoing bariatric surgery indicate that there is a return toward hypertensive levels of blood pressure once the weight has reached a plateau after the sustained weight loss that follows such operations.4
These observations regarding glycemic control and hypertension may be considered to reveal an interaction between the short-term effects of a negative energy balance and the effects of the loss of adiposity. There is a practical limit to this line of reasoning, however, since a negative energy balance induces weight loss, and it is arguably artificial in most circumstances to dissociate the achievement or maintenance of a negative energy balance from its consequence of weight loss.
In this issue of the Journal, Klein et al. (pages 2549–2557) present the findings of a study of the metabolic effects of liposuction in obese women — liposuction representing one way of dissociating a negative energy balance from weight loss. Abdominal liposuction was used to remove approximately 9 kg of fat from subjects with a normal glucose tolerance and approximately 10 kg of fat from subjects with type 2 diabetes. This amount of liposuction represented a sizable reduction of subcutaneous abdominal adiposity, since nearly one fifth of the total adipose tissue was removed from each subject. Despite this surgically induced decrease in adiposity, the insulin sensitivity of the study participants did not change, according to a detailed analysis of insulin action on muscle, liver, and adipose tissue. In addition, the plasma glucose, insulin, and lipoprotein levels did not change after large-volume liposuction.
These results might be considered first within the context of energy balance. Despite the surgical removal of a large volume of adipose tissue, and therefore the removal of a considerable amount of stored energy, the daily net energy balance between dietary intake and energy expenditure was not affected. Thus, one might view the absence of an effect of liposuction on insulin resistance as an indication of what happens when a negative energy balance is dissociated from weight loss. The lack of effect of large-volume liposuction may indicate that at least a slightly negative energy balance must be achieved in order to attain metabolic improvement of obesity-related insulin resistance.
Another way to interpret the findings of Klein et al. merits consideration: the type of adipose tissue that was removed, or more specifically, its location, may be the key. Subcutaneous abdominal adipose tissue was removed by liposuction in this study. Yet many (although certainly not all) clinical investigators have observed that visceral adiposity is more strongly associated with insulin resistance. In studies in animals, the surgical resection of visceral adipose tissue has yielded marked and nearly immediate improvements in insulin resistance,5 whereas the removal of equivalent amounts of subcutaneous adipose tissue has had little effect. The explanation for the strong association between visceral adiposity and insulin resistance in obesity is not fully understood but may be related, at least in part, to the release of fatty acids into the portal circulation.
Another consideration is that adipose tissue has endocrine functions by virtue of synthesizing and secreting leptin, adiponectin, resistin, and numerous other factors including cytokines such as tumor necrosis factor (TNF-) and interleukin-6. In the study by Klein et al., plasma concentrations of C-reactive protein, interleukin-6, TNF-, and adiponectin were not changed after the surgical removal of subcutaneous fat tissue. It remains to be determined whether the removal of an equivalent amount of visceral adipose tissue might have a more robust effect on the metabolic abnormalities of obesity. It may well be that a negative energy balance permits a fairly rapid improvement in fat content within liver and muscle, depots of stored energy that have been shown to affect the severity of insulin resistance, whereas the surgical removal of adipose tissue may not evoke these changes.
Amidst the growing public concern about the high prevalence of obesity and the interest within the medical community in developing effective treatments for obesity and its many health consequences, there has been a pronounced increase in the use of surgical approaches to weight loss and the removal of adipose tissue. It is important to ascertain the health benefits and risks of such surgical interventions. The clinical investigation by Klein et al. provides useful objective evidence that even large-volume liposuction has little effect on insulin sensitivity or cardiovascular risk factors and offers a new perspective on the interaction between the loss of adiposity and a negative energy balance in mediating the salutary effect of weight-loss interventions for obesity.
Source Information
From the Obesity and Nutrition Research Center, University of Pittsburgh Medical Center, Pittsburgh.
References
Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
Henry RR, Scheaffer L, Olefsky JM. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1985;61:917-925.
Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons M. Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993;77:1287-1293.
Sjostrom CD, Peltonen M, Wedel H, Sjostrom L. Differentiated long-term effects of intentional weight loss on diabetes and hypertension. Hypertension 2000;36:20-25.
Gabriely I, Ma XH, Yang XM, et al. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes 2002;51:2951-2958.(David E. Kelley, M.D.)
It has been argued that a substantial portion of the metabolic benefits that occur in response to weight loss are directly related to the effects of a negative energy balance. Glucose and insulin homeostasis provide robust biologic markers of the effects of interventions in type 2 diabetes. Henry et al. were among the first to observe that hyperglycemia improves rapidly during caloric restriction, outpacing the rate of weight loss.2 Later studies confirmed their observations and revealed that approximately half of the improvement in insulin resistance and glycemic control induced by the loss of 15 percent of total body weight was achieved during the first week in which there was a negative energy balance.3 The actual fat loss is typically quite small during short periods of caloric restriction; weight loss during such periods is achieved largely through the increased excretion of sodium and water, not through the loss of adipose tissue.
These and additional studies suggested that a substantial proportion of the beneficial metabolic effects of weight loss on insulin resistance and hyperglycemia in type 2 diabetes may be more correctly attributed to the effects of a negative energy balance. Similar observations have been made concerning hypertension: much of the decrease in blood pressure occurs fairly rapidly in response to a negative energy balance. Observations in patients undergoing bariatric surgery indicate that there is a return toward hypertensive levels of blood pressure once the weight has reached a plateau after the sustained weight loss that follows such operations.4
These observations regarding glycemic control and hypertension may be considered to reveal an interaction between the short-term effects of a negative energy balance and the effects of the loss of adiposity. There is a practical limit to this line of reasoning, however, since a negative energy balance induces weight loss, and it is arguably artificial in most circumstances to dissociate the achievement or maintenance of a negative energy balance from its consequence of weight loss.
In this issue of the Journal, Klein et al. (pages 2549–2557) present the findings of a study of the metabolic effects of liposuction in obese women — liposuction representing one way of dissociating a negative energy balance from weight loss. Abdominal liposuction was used to remove approximately 9 kg of fat from subjects with a normal glucose tolerance and approximately 10 kg of fat from subjects with type 2 diabetes. This amount of liposuction represented a sizable reduction of subcutaneous abdominal adiposity, since nearly one fifth of the total adipose tissue was removed from each subject. Despite this surgically induced decrease in adiposity, the insulin sensitivity of the study participants did not change, according to a detailed analysis of insulin action on muscle, liver, and adipose tissue. In addition, the plasma glucose, insulin, and lipoprotein levels did not change after large-volume liposuction.
These results might be considered first within the context of energy balance. Despite the surgical removal of a large volume of adipose tissue, and therefore the removal of a considerable amount of stored energy, the daily net energy balance between dietary intake and energy expenditure was not affected. Thus, one might view the absence of an effect of liposuction on insulin resistance as an indication of what happens when a negative energy balance is dissociated from weight loss. The lack of effect of large-volume liposuction may indicate that at least a slightly negative energy balance must be achieved in order to attain metabolic improvement of obesity-related insulin resistance.
Another way to interpret the findings of Klein et al. merits consideration: the type of adipose tissue that was removed, or more specifically, its location, may be the key. Subcutaneous abdominal adipose tissue was removed by liposuction in this study. Yet many (although certainly not all) clinical investigators have observed that visceral adiposity is more strongly associated with insulin resistance. In studies in animals, the surgical resection of visceral adipose tissue has yielded marked and nearly immediate improvements in insulin resistance,5 whereas the removal of equivalent amounts of subcutaneous adipose tissue has had little effect. The explanation for the strong association between visceral adiposity and insulin resistance in obesity is not fully understood but may be related, at least in part, to the release of fatty acids into the portal circulation.
Another consideration is that adipose tissue has endocrine functions by virtue of synthesizing and secreting leptin, adiponectin, resistin, and numerous other factors including cytokines such as tumor necrosis factor (TNF-) and interleukin-6. In the study by Klein et al., plasma concentrations of C-reactive protein, interleukin-6, TNF-, and adiponectin were not changed after the surgical removal of subcutaneous fat tissue. It remains to be determined whether the removal of an equivalent amount of visceral adipose tissue might have a more robust effect on the metabolic abnormalities of obesity. It may well be that a negative energy balance permits a fairly rapid improvement in fat content within liver and muscle, depots of stored energy that have been shown to affect the severity of insulin resistance, whereas the surgical removal of adipose tissue may not evoke these changes.
Amidst the growing public concern about the high prevalence of obesity and the interest within the medical community in developing effective treatments for obesity and its many health consequences, there has been a pronounced increase in the use of surgical approaches to weight loss and the removal of adipose tissue. It is important to ascertain the health benefits and risks of such surgical interventions. The clinical investigation by Klein et al. provides useful objective evidence that even large-volume liposuction has little effect on insulin sensitivity or cardiovascular risk factors and offers a new perspective on the interaction between the loss of adiposity and a negative energy balance in mediating the salutary effect of weight-loss interventions for obesity.
Source Information
From the Obesity and Nutrition Research Center, University of Pittsburgh Medical Center, Pittsburgh.
References
Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
Henry RR, Scheaffer L, Olefsky JM. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1985;61:917-925.
Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons M. Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993;77:1287-1293.
Sjostrom CD, Peltonen M, Wedel H, Sjostrom L. Differentiated long-term effects of intentional weight loss on diabetes and hypertension. Hypertension 2000;36:20-25.
Gabriely I, Ma XH, Yang XM, et al. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes 2002;51:2951-2958.(David E. Kelley, M.D.)