- Email: [email protected]
Special issue introduction
Physiology & Behavior 83 (2004) 545 – 547
Editorial
Special issue introduction
Over the past 30 years, the concept of healthy eating promulgated by governmental, health, and private organizations (e.g., commercial weight loss programs, bhealth and beautyQ magazines) has often become a dictate to avoid dietary fat. The main bases for this recommendation are that (1) saturated fat increases blood cholesterol, which is a risk factor for promoting cardiovascular disease, and (2) a high level of dietary fat is considered to be a major risk factor for the development of obesity, which is in turn associated with insulin resistance and chronic diseases, such as type 2 diabetes, hyperlipidemia, hypertension, coronary heart disease, and an increased risk of certain forms of cancer. However, the science of dietary fat is not as simple as it once appeared [21]. Although fat intake in some industrialized countries has actually dropped in recent years, obesity continues to increase at an alarming rate, suggesting that other factors are important. Indeed, obesity has replaced undernutrition and infectious diseases as the major health problem in industrialized countries and, together with its associated risk factors, has been estimated to account for 2– 7% of all health costs in developed countries [22]. It is controversial as to whether people on low-fat diets lose more weight and are better able to maintain the reduced body weight than people on other diets [1,2,7,9,17,18,20,25]. One reason for some of the seemingly paradoxical results may be the fact that for most people, even if they achieve a successful focus on eating less fat, usually compensate by eating more carbohydrates and consequently maintain total energy intake nearly unchanged. A worrisome aspect of this fat–carbohydrate tradeoff is the potentially negative metabolic effects of diets high in carbohydrates [24,26], effects which might favor weight gain in some individuals more than diets with moderately high amount of dietary fats [4]. Furthermore, it should not be forgotten that some fats have beneficial effects on health and energy balance. For instance, conjugated linoleic acid (CLA) isomers may have only limited effects on body weight [14,23] but have a number of other health effects, including reducing the risk of cancer and improving glucose tolerance [12,19]. Intake of polyunsaturated fatty acids (PUFAs) may promote long-chain fatty acid oxidation and thus limit rather than enhance energy intake [6,15]. Finally, there are several well0031-9384/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2004.09.014
controlled studies indicating that low-carbohydrate high-fat diets actually decrease rather than increase energy intake and body weight without overt negative effects on metabolism and the cardiovascular system (e.g., Refs. [1,5,9]). These controversies and uncertainties suggested to us that a comprehensive evaluation of the role of dietary fat in the control of energy balance and health would be timely. This was the aim of a workshop titled bDietary fat and energy balance—myths and factsQ, which was held July 7– 11, 2003, in Ascona, Switzerland, at the Centro Stefano Franscini of the Swiss Federal Institute of Technology. The workshop brought together about 40 expert clinicians and researchers from around the world, who in a week of seminars and discussions attempted to identify, evaluate, and integrate several important aspects of the interactions between dietary fat and bodily function at the molecular, cellular, and systemic levels and their health implications. The 14 reviews collected in this special section/issue of Physiology and Behavior provide a representative overview of the results of this workshop. These reviews reflect the synthetic and translational spirit of the workshop. One consequence of this is that they cannot be ordered in a strictly linear fashion; rather, most of the authors illuminate various, often disparate, and sometime even apparently contradictory aspects of dietary fat through the prisms of their own special expertise. This, we take as signs both of the complexity of the problems addressed and of the success of our multidisciplinary, dialectic approach. The areas reviewed in the most depth cover three general themes: epidemiology and health, metabolism or nutritional physiology, and the control of fat ingestion. The challenge of the topic is made clear in the first four contributions, which address epidemiological and health aspects related to overconsumption of fat. George Bray and colleagues review the epidemiological evidence for a relationship between high fat intake and obesity, emphasizing that dietary fat is an important contributor to obesity in some people, in particular when physical activity is low. Yves Schqtz distinguishes between short-, medium-, and long-term effects of dietary fat, arguing for a physiological bfat balanceQ that is closely related to energy balance when considered over months or years. He also touches the
546
Editorial
controversial issue of de novo lipogenesis after acute or prolonged carbohydrate overeating, and whether de novo lipogenesis per se is a risk factor for the development of obesity. Caspar Wenk’s perspective is counterpoint. Paralleling the herald cry of Willett [25]; Wenk emphasizes the often-neglected fact that deposition of absorbed fat in excess of oxidized amount occurs only if total energy intake is above needs—i.e., when the individual is in positive energy balance. In this far-reaching review, Wenk also highlights the difficulties of providing accurate epidemiological data on fat intake, reviews the different nutritional implications of fats of various types, and places this all in the not very encouraging context of the general public’s poor understanding of the basic realities of nutrition. Steve Woods and his colleagues turn the discussion of these issues to animal basic research. In their rat model, the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Relative to animals consuming diets low in fat, animals eating a highfat diet weigh more, have more carcass fat, are hyperinsulinemic, and hyperleptinemic, as well as insulin resistant. Woods et al. discuss several important research opportunities afforded by this model. The next four reviews focus on various systemic physiological consequences of fat ingestion and body adiposity related to energy balance. Margriet WesterterpPlantenga revisits the effects of dietary fatty acids on thermogenesis, fat oxidation, and body composition in humans. She also introduces the question of the short-term effects of fat on food intake, which is analyzed further by several authors in the last group of papers. WesterterpPlantenga emphasizes that many reported physiological effects of fat depend critically on the time span covered by the study; for example, ingestion of fat is commonly thought to inhibit future eating less than ingestion of carbohydrates or protein, but this may be mainly because the effect of fat is slower. She also discusses the effects of fat replacements and of diacylglycerol compared to triacylglycerol intake. Next, Abdul Dulloo focuses on the other side of the energy balance equation, i.e., energy expenditure. He expertly reassesses what constitutes adaptive changes in thermogenesis, the roles of the sympathetic nervous system, and of the uncoupling proteins (UCP1, UCP2, UCP3, UCP5) as the efferent effector components of the classical one-control system for adaptive thermogenesis and fat oxidation. He argues that these metabolic pathways may be particularly important when energy intake is stimulated for reasons unrelated to dietary fat, for example, by increases in eating that are compensatory to low concentrations of dietary protein. The interconnected effects of fat and carbohydrate are the focus of the last two papers in this section. Paolo Colombani introduces the concept of the glycemic index [7,26], discussing it in the context of the current dietary guidelines, and emphasizing that the energy density and the macronutrient composition of food may not always provide
a sufficient explanation for body weight gain. Finally, Richard Stfckli and Ulrich Keller bring the discussion to human clinical issues, covering the effects of dietary fat on insulin sensitivity and on the development of type 2 diabetes. The last set of six papers focuses mainly on the effects of dietary fat on future eating. These papers are organized in physiological order, following the passage of ingested fat from the gut through the organism until it is oxidized or deposited as adipose tissue. The first three review the effects of fat on various gastrointestinal bsatiety peptides.Q Christoph Beglinger and Lukas Degen discuss the satiating effect of the intestinal peptide cholecystokinin (CCK), and also touch upon the recent work with peptide YY, focusing especially on their important work on the satiating actions of CCK in humans. Then, Charlotte Erlanson-Albertsson and her colleagues briefly rehearse current knowledge on the procolipase-derived pentapeptide enterostatin and introduce two new mechanisms that might mediate its feedinginhibitory effect. In the third paper of this series, Patrick Tso and his colleagues present a comprehensive review on apolipoprotein A-IV (apo A-IV), including the accumulating evidence for a centrally mediated satiating effect of apo A-IV, especially the exciting finding that intrahypothalamic administration of antiserum to apo A-IV increases food intake. Next, Monika Leonhardt and Wolfgang Langhans discuss the pros and cons for a role of hepatic fatty acid oxidation in the control of eating, pointing out that evidence from several studies suggests that inhibition of fatty acid oxidation leads to a stimulation of feeding, but that despite several attempts, it is as yet unclear whether stimulation of fatty acid oxidation can inhibit eating. Their conclusion is that new approaches are necessary to address this question. The penultimate paper in this group, by Hans Hauner, turned the discussion to the role of the adipose tissue itself as a controller of eating and metabolism. This concept, of course, originated with the classical work of Gordon Kennedy 50 years ago [13] and more recently has been the focus of a tremendous expansion in knowledge and thinking triggered by the watershed discovery of leptin 10 years ago [2]. More recently, evidence has accumulated that several other factors/molecules derived from adipose tissue, if not necessarily from fat cells, affect energy balance [8]. Hauner describes emerging knowledge about several such factors in an updated review of the role of adipose tissue in energy balance. Finally, Nori Geary introduces an additional important, if often overlooked dimension, to the discussion of the effects of fat on appetite, that of sex differences. After first outlining the remarkable sex differences in frequency of extreme obesity, he reviews the often fragmentary evidence in humans and animals that the various controls of eating discussed in many of the other papers are sexually differentiated, and he emphasizes the need for further, more systematic work in this area. In sum, the papers in this special issue of Physiology and Behavior titled bDietary fat and energy balance—myths and factsQ present a multidisciplinary, integrated approach to
Editorial
addressing many aspects of important, but poorly understood, relations among dietary fat, energy balance, and health. We hope the readers find this an interesting, timely, and useful contribution to the ongoing discussion of this very important scientific and social problem [3,10,11,16]. We also want to thank all contributing authors for their efforts, and Sara Purdy, the Production editor of Elsevier Science, for her patience and unwavering support, which were vitally necessary to the success of the project.
Acknowledgements Finally, we gratefully acknowledge the Centro Stefano Franscini (ETH), Masterfoods, Nestec AC, Proctor & Gamble, the Swiss Academy of Sciences, Swiss Milk Producers and the Swiss National Science Foundation, who provided financial and material support for the workshop.
References [1] Acheson KJ. Carbohydrate and weight control: where do we stand? Curr Opin Clin Nutr Metabol Care 2004;7:485 – 92. [2] Astrup A, Buemann B, Flint A, Raben A. Low-fat diets and energy balance: how does the evidence stand in 2002? Proc Nutr Soc 2002; 61:299 – 309. [3] Berthoud HR, Scheurink AJW. Ingestive behavior and the obesity crisis. Physiol Behav 2004;81:717 – 8. [4] Brand-Miller JC, Holt SHA, Pawlak DB, McMillan J. Glycemic index and obesity. Am J Clin Nutr 2002;76:281S – 5S. [5] Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003;88:1617 – 23. [6] Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr 2001;131:1129 – 32. [7] Finer N. Low-calorie diets and sustained weight loss. Obes Res 2001; 9:290S – 4S. [8] Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell 2004;116:337 – 50. [9] Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al. A randomized trial of a low-carbohydrate diet for obesity. New Engl J Med 2003;348:2082 – 90. [10] Friedman JM. Modern science versus the stigma of obesity. Nat Med 2004;10:563 – 9. [11] Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the environment: where do we go from here? Science 2003;299:853 – 5.
547
[12] Jahreis G, Kraft J, Tischendorf F, Schone F, von Loeffelholz C. Conjugated linoleic acids: physiological effects in animal and man with special regard to body composition. Eur J Lipid Sci Technol 2000;102:695 – 703. [13] Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond, B 1953;140:578 – 96. [14] Larsen TM, Toubro S, Astrup A. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J Lipid Res 2003;44:2234 – 41. [15] Nakamura MT, Cho HP, Xu J, Tang ZR, Clarke SD. Metabolism and functions of highly unsaturated fatty acids: an update. Lipids 2001;36: 961 – 4. [16] Pi-Sunyer X. A clinical view of the obesity problem. Science 2003; 299:859 – 60. [17] Poppitt SD, Keogh GF, Prentice AM, Williams DEM, Sonnemans EEJ, Valk EEJ, et al. Long-term effects of ad libitum low-fat, highcarbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome. Am J Clin Nutr 2002;75:11 – 20. [18] Roberts SB, McCrory MA, Saltzman E. The influence of dietary composition on energy intake and body weight. J Am Coll Nutr 2002; 21:140S – 5S. [19] Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, et al. Isomer-specific antidiabetic properties of conjugated linoleic acid—improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes 2001;50:1149 – 57. [20] Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. New Engl J Med 2003;348:2074 – 81. [21] Taubes G. The soft science of dietary fat. Science 2001;291:2536. [22] Thompson D, Wolf AM. The medical-care cost burden of obesity. Obes Rev 2001;2:189 – 97. [23] Wang YW, Jones PJH. Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes 2004;28:941 – 55. [24] Willett W, Manson J, Liu SM. Glycemic index, glycemic load, and risk of type 2 diabetes. Am J Clin Nutr 2002;76:274S – 80S. [25] Willett WC, Leibel RL. Dietary fat is not a major determinant of body fat. Am J Med 2002;113:47 – 59. [26] Wolever TMS. Carbohydrate and the regulation of blood glucose and metabolism. Nutr Rev 2003;61:S40–8.
Wolfgang Langhans* Nori Geary Swiss Federal Institute of Technology (ETH), Schwerzenbach, Switzerland E-mail address: [email protected]. *Corresponding author. Tel.: +41 1 655 7420; fax: +41 1 655 7201. Stephen C. Woods University of Cincinnati, Cincinnati, OH, United Sates 17 September 2004
Editorial
Special issue introduction
Over the past 30 years, the concept of healthy eating promulgated by governmental, health, and private organizations (e.g., commercial weight loss programs, bhealth and beautyQ magazines) has often become a dictate to avoid dietary fat. The main bases for this recommendation are that (1) saturated fat increases blood cholesterol, which is a risk factor for promoting cardiovascular disease, and (2) a high level of dietary fat is considered to be a major risk factor for the development of obesity, which is in turn associated with insulin resistance and chronic diseases, such as type 2 diabetes, hyperlipidemia, hypertension, coronary heart disease, and an increased risk of certain forms of cancer. However, the science of dietary fat is not as simple as it once appeared [21]. Although fat intake in some industrialized countries has actually dropped in recent years, obesity continues to increase at an alarming rate, suggesting that other factors are important. Indeed, obesity has replaced undernutrition and infectious diseases as the major health problem in industrialized countries and, together with its associated risk factors, has been estimated to account for 2– 7% of all health costs in developed countries [22]. It is controversial as to whether people on low-fat diets lose more weight and are better able to maintain the reduced body weight than people on other diets [1,2,7,9,17,18,20,25]. One reason for some of the seemingly paradoxical results may be the fact that for most people, even if they achieve a successful focus on eating less fat, usually compensate by eating more carbohydrates and consequently maintain total energy intake nearly unchanged. A worrisome aspect of this fat–carbohydrate tradeoff is the potentially negative metabolic effects of diets high in carbohydrates [24,26], effects which might favor weight gain in some individuals more than diets with moderately high amount of dietary fats [4]. Furthermore, it should not be forgotten that some fats have beneficial effects on health and energy balance. For instance, conjugated linoleic acid (CLA) isomers may have only limited effects on body weight [14,23] but have a number of other health effects, including reducing the risk of cancer and improving glucose tolerance [12,19]. Intake of polyunsaturated fatty acids (PUFAs) may promote long-chain fatty acid oxidation and thus limit rather than enhance energy intake [6,15]. Finally, there are several well0031-9384/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2004.09.014
controlled studies indicating that low-carbohydrate high-fat diets actually decrease rather than increase energy intake and body weight without overt negative effects on metabolism and the cardiovascular system (e.g., Refs. [1,5,9]). These controversies and uncertainties suggested to us that a comprehensive evaluation of the role of dietary fat in the control of energy balance and health would be timely. This was the aim of a workshop titled bDietary fat and energy balance—myths and factsQ, which was held July 7– 11, 2003, in Ascona, Switzerland, at the Centro Stefano Franscini of the Swiss Federal Institute of Technology. The workshop brought together about 40 expert clinicians and researchers from around the world, who in a week of seminars and discussions attempted to identify, evaluate, and integrate several important aspects of the interactions between dietary fat and bodily function at the molecular, cellular, and systemic levels and their health implications. The 14 reviews collected in this special section/issue of Physiology and Behavior provide a representative overview of the results of this workshop. These reviews reflect the synthetic and translational spirit of the workshop. One consequence of this is that they cannot be ordered in a strictly linear fashion; rather, most of the authors illuminate various, often disparate, and sometime even apparently contradictory aspects of dietary fat through the prisms of their own special expertise. This, we take as signs both of the complexity of the problems addressed and of the success of our multidisciplinary, dialectic approach. The areas reviewed in the most depth cover three general themes: epidemiology and health, metabolism or nutritional physiology, and the control of fat ingestion. The challenge of the topic is made clear in the first four contributions, which address epidemiological and health aspects related to overconsumption of fat. George Bray and colleagues review the epidemiological evidence for a relationship between high fat intake and obesity, emphasizing that dietary fat is an important contributor to obesity in some people, in particular when physical activity is low. Yves Schqtz distinguishes between short-, medium-, and long-term effects of dietary fat, arguing for a physiological bfat balanceQ that is closely related to energy balance when considered over months or years. He also touches the
546
Editorial
controversial issue of de novo lipogenesis after acute or prolonged carbohydrate overeating, and whether de novo lipogenesis per se is a risk factor for the development of obesity. Caspar Wenk’s perspective is counterpoint. Paralleling the herald cry of Willett [25]; Wenk emphasizes the often-neglected fact that deposition of absorbed fat in excess of oxidized amount occurs only if total energy intake is above needs—i.e., when the individual is in positive energy balance. In this far-reaching review, Wenk also highlights the difficulties of providing accurate epidemiological data on fat intake, reviews the different nutritional implications of fats of various types, and places this all in the not very encouraging context of the general public’s poor understanding of the basic realities of nutrition. Steve Woods and his colleagues turn the discussion of these issues to animal basic research. In their rat model, the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Relative to animals consuming diets low in fat, animals eating a highfat diet weigh more, have more carcass fat, are hyperinsulinemic, and hyperleptinemic, as well as insulin resistant. Woods et al. discuss several important research opportunities afforded by this model. The next four reviews focus on various systemic physiological consequences of fat ingestion and body adiposity related to energy balance. Margriet WesterterpPlantenga revisits the effects of dietary fatty acids on thermogenesis, fat oxidation, and body composition in humans. She also introduces the question of the short-term effects of fat on food intake, which is analyzed further by several authors in the last group of papers. WesterterpPlantenga emphasizes that many reported physiological effects of fat depend critically on the time span covered by the study; for example, ingestion of fat is commonly thought to inhibit future eating less than ingestion of carbohydrates or protein, but this may be mainly because the effect of fat is slower. She also discusses the effects of fat replacements and of diacylglycerol compared to triacylglycerol intake. Next, Abdul Dulloo focuses on the other side of the energy balance equation, i.e., energy expenditure. He expertly reassesses what constitutes adaptive changes in thermogenesis, the roles of the sympathetic nervous system, and of the uncoupling proteins (UCP1, UCP2, UCP3, UCP5) as the efferent effector components of the classical one-control system for adaptive thermogenesis and fat oxidation. He argues that these metabolic pathways may be particularly important when energy intake is stimulated for reasons unrelated to dietary fat, for example, by increases in eating that are compensatory to low concentrations of dietary protein. The interconnected effects of fat and carbohydrate are the focus of the last two papers in this section. Paolo Colombani introduces the concept of the glycemic index [7,26], discussing it in the context of the current dietary guidelines, and emphasizing that the energy density and the macronutrient composition of food may not always provide
a sufficient explanation for body weight gain. Finally, Richard Stfckli and Ulrich Keller bring the discussion to human clinical issues, covering the effects of dietary fat on insulin sensitivity and on the development of type 2 diabetes. The last set of six papers focuses mainly on the effects of dietary fat on future eating. These papers are organized in physiological order, following the passage of ingested fat from the gut through the organism until it is oxidized or deposited as adipose tissue. The first three review the effects of fat on various gastrointestinal bsatiety peptides.Q Christoph Beglinger and Lukas Degen discuss the satiating effect of the intestinal peptide cholecystokinin (CCK), and also touch upon the recent work with peptide YY, focusing especially on their important work on the satiating actions of CCK in humans. Then, Charlotte Erlanson-Albertsson and her colleagues briefly rehearse current knowledge on the procolipase-derived pentapeptide enterostatin and introduce two new mechanisms that might mediate its feedinginhibitory effect. In the third paper of this series, Patrick Tso and his colleagues present a comprehensive review on apolipoprotein A-IV (apo A-IV), including the accumulating evidence for a centrally mediated satiating effect of apo A-IV, especially the exciting finding that intrahypothalamic administration of antiserum to apo A-IV increases food intake. Next, Monika Leonhardt and Wolfgang Langhans discuss the pros and cons for a role of hepatic fatty acid oxidation in the control of eating, pointing out that evidence from several studies suggests that inhibition of fatty acid oxidation leads to a stimulation of feeding, but that despite several attempts, it is as yet unclear whether stimulation of fatty acid oxidation can inhibit eating. Their conclusion is that new approaches are necessary to address this question. The penultimate paper in this group, by Hans Hauner, turned the discussion to the role of the adipose tissue itself as a controller of eating and metabolism. This concept, of course, originated with the classical work of Gordon Kennedy 50 years ago [13] and more recently has been the focus of a tremendous expansion in knowledge and thinking triggered by the watershed discovery of leptin 10 years ago [2]. More recently, evidence has accumulated that several other factors/molecules derived from adipose tissue, if not necessarily from fat cells, affect energy balance [8]. Hauner describes emerging knowledge about several such factors in an updated review of the role of adipose tissue in energy balance. Finally, Nori Geary introduces an additional important, if often overlooked dimension, to the discussion of the effects of fat on appetite, that of sex differences. After first outlining the remarkable sex differences in frequency of extreme obesity, he reviews the often fragmentary evidence in humans and animals that the various controls of eating discussed in many of the other papers are sexually differentiated, and he emphasizes the need for further, more systematic work in this area. In sum, the papers in this special issue of Physiology and Behavior titled bDietary fat and energy balance—myths and factsQ present a multidisciplinary, integrated approach to
Editorial
addressing many aspects of important, but poorly understood, relations among dietary fat, energy balance, and health. We hope the readers find this an interesting, timely, and useful contribution to the ongoing discussion of this very important scientific and social problem [3,10,11,16]. We also want to thank all contributing authors for their efforts, and Sara Purdy, the Production editor of Elsevier Science, for her patience and unwavering support, which were vitally necessary to the success of the project.
Acknowledgements Finally, we gratefully acknowledge the Centro Stefano Franscini (ETH), Masterfoods, Nestec AC, Proctor & Gamble, the Swiss Academy of Sciences, Swiss Milk Producers and the Swiss National Science Foundation, who provided financial and material support for the workshop.
References [1] Acheson KJ. Carbohydrate and weight control: where do we stand? Curr Opin Clin Nutr Metabol Care 2004;7:485 – 92. [2] Astrup A, Buemann B, Flint A, Raben A. Low-fat diets and energy balance: how does the evidence stand in 2002? Proc Nutr Soc 2002; 61:299 – 309. [3] Berthoud HR, Scheurink AJW. Ingestive behavior and the obesity crisis. Physiol Behav 2004;81:717 – 8. [4] Brand-Miller JC, Holt SHA, Pawlak DB, McMillan J. Glycemic index and obesity. Am J Clin Nutr 2002;76:281S – 5S. [5] Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003;88:1617 – 23. [6] Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr 2001;131:1129 – 32. [7] Finer N. Low-calorie diets and sustained weight loss. Obes Res 2001; 9:290S – 4S. [8] Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell 2004;116:337 – 50. [9] Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al. A randomized trial of a low-carbohydrate diet for obesity. New Engl J Med 2003;348:2082 – 90. [10] Friedman JM. Modern science versus the stigma of obesity. Nat Med 2004;10:563 – 9. [11] Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the environment: where do we go from here? Science 2003;299:853 – 5.
547
[12] Jahreis G, Kraft J, Tischendorf F, Schone F, von Loeffelholz C. Conjugated linoleic acids: physiological effects in animal and man with special regard to body composition. Eur J Lipid Sci Technol 2000;102:695 – 703. [13] Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond, B 1953;140:578 – 96. [14] Larsen TM, Toubro S, Astrup A. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J Lipid Res 2003;44:2234 – 41. [15] Nakamura MT, Cho HP, Xu J, Tang ZR, Clarke SD. Metabolism and functions of highly unsaturated fatty acids: an update. Lipids 2001;36: 961 – 4. [16] Pi-Sunyer X. A clinical view of the obesity problem. Science 2003; 299:859 – 60. [17] Poppitt SD, Keogh GF, Prentice AM, Williams DEM, Sonnemans EEJ, Valk EEJ, et al. Long-term effects of ad libitum low-fat, highcarbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome. Am J Clin Nutr 2002;75:11 – 20. [18] Roberts SB, McCrory MA, Saltzman E. The influence of dietary composition on energy intake and body weight. J Am Coll Nutr 2002; 21:140S – 5S. [19] Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, et al. Isomer-specific antidiabetic properties of conjugated linoleic acid—improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes 2001;50:1149 – 57. [20] Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. New Engl J Med 2003;348:2074 – 81. [21] Taubes G. The soft science of dietary fat. Science 2001;291:2536. [22] Thompson D, Wolf AM. The medical-care cost burden of obesity. Obes Rev 2001;2:189 – 97. [23] Wang YW, Jones PJH. Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes 2004;28:941 – 55. [24] Willett W, Manson J, Liu SM. Glycemic index, glycemic load, and risk of type 2 diabetes. Am J Clin Nutr 2002;76:274S – 80S. [25] Willett WC, Leibel RL. Dietary fat is not a major determinant of body fat. Am J Med 2002;113:47 – 59. [26] Wolever TMS. Carbohydrate and the regulation of blood glucose and metabolism. Nutr Rev 2003;61:S40–8.
Wolfgang Langhans* Nori Geary Swiss Federal Institute of Technology (ETH), Schwerzenbach, Switzerland E-mail address: [email protected]. *Corresponding author. Tel.: +41 1 655 7420; fax: +41 1 655 7201. Stephen C. Woods University of Cincinnati, Cincinnati, OH, United Sates 17 September 2004