Bieber Abstracts

Jean-Pierre Flatt

Professor Emeritus

Department of Biochemistry and Molecular Pharmacology

University of Massachusetts Medical Center

Worcester, MA 01655-0103

USA

ABSTRACT

Keynote: Obesity--An Overview.

In the United States, the BMI (Body Mass Index = Wt[kg]/Ht[m]²) of men has increased by 3 to 4 units during the last 100 years. The rise in the prevalence of overweight (BMI 25 to 30) and of obesity (BMI > 30) during the last two decades is now recognized as a worldwide problem, with ominous implications for public health and health-related costs. The parameters generally considered to explain increases in BMI and in the prevalence of obesity include increased food availability, increased dietary fat content, greater energy density of foods, and decreased physical activity. Yet, during the last 20 years, these parameters appear to have remained fairly stable in the United States and in other affluent countries.

The predisposition toward obesity is also influenced by genetic factors, but the high prevalence of obesity in affluent societies makes it difficult to assess the relative importance of inherited and non-inherited factors. Among the latter, it is helpful to distinguish between 'circumstantial' factors, which together with genetic factors are responsible for individual variability of BMI around the mean, and 'environmental' factors which cause mean BMI to rise, such as moving from a situation with occasional food scarcity into affluent conditions. This is a unidirectional effect, and its contribution to the development of obesity is underestimated, when the relative importance of inherited and non-inherited factors are assessed by their contributions to the variance about the mean.

Because of their hydrophobic nature, lipids can be stored far more efficiently than glycogen (the animal equivalent of starch), which retains 3 g of water per gram. In man, the fat stored in adipose tissue provides an energy reserve that is typically two orders of magnitude greater than the body's limited glycogen stores. Evolution was therefore compelled to develop regulatory mechanisms that give higher priority to the control of its carbohydrate economy, than to the control of fat metabolism. Thus consumption of carbohydrate elicits a prompt increase in glucose oxidation (with a concomitant decrease in fat oxidation), whereas consumption of fat does not lead to increased fat oxidation. While progressive increases in the fat mass do promote fat oxidation, this is a long-term effect and it is less powerful than the influence of the carbohydrate supply on the relative contributions made by fat and glucose to the fuel mix oxidized.

In trying to understand body weight regulation, it is important to realize that the steady-state of weight maintenance is only possible when the fuel mix oxidized matches the nutrient mixture consumed, in amount AND composition. This suggests that recent increases in the prevalence of obesity may be related to a trend of habitually maintaining glycogen levels within a slightly higher range, as this would require an expansion of the fat mass, to maintain fat oxidation rates commensurate with fat intake. A further decline in physical activity could also be involved in causing increased fatness, in part by causing less glycogen depletion between meals. While the impact of vigorous physical activity in preventing excess fat accumulation is readily recognized, the influence of modest levels of physical activities is less obvious. However, measurements of inactivity are more telling in this respect, and they show that hours spent watching TV or sitting in front of a computer are correlated with fat accumulation in children.

Inherited traits are often thought to influence obesity by causing resting metabolic rates to be unusually low. When appropriately corrected for differences in body size and age, the observed differences are rather small and, in any case, they are more than offset by the increase in energy expenditure associated with a larger body size. The size of the lean body mass is in effect the main predictor of resting energy expenditure. In the NHANES2 data, height accounts for 10-16% of the variance in lean body mass, yet difference in stature explain less than 1% of the variance in body fat content. Thus differences in resting metabolic rates appear to have a much smaller impact on obesity than commonly believed. By contrast, inherited traits influencing energy expenditure by affecting individual predispositions toward physical activity can be expected to have a substantial impact on adiposity. Inherited traits could also exert major leverage on body weights by affecting the relative rates of carbohydrate and fat oxidation, particularly by altering the influence of the adipose tissue mass on the relative use of fatty acids and glucose. Such effects have been difficult to prove, because their impact on the fuel ratio oxidized is much smaller than the effects thereon of the large daily variations in food intake and physical activity which occur in free-living individuals.

When considered over the long run, food intake regulation leads to a remarkably good adjustment of energy intake to energy expenditure, as energy imbalances are generally less than 1 to 2% of energy turnover, when considered over periods of a year. The fact that short-term variations in the energy balance are large shows not only that they are readily tolerated, but also that one cannot therefore expect physiological regulation of food intake to account for a large part of the variance in daily food consumption. This has made it very difficult to gain a realistic understanding of food intake regulation and this constitutes a big obstacle in tackling the obesity problem.

The success of drugs in controlling body weight has been limited so far, perhaps because increasing adiposity seems to be a natural consequence of biological evolution, followed by economic evolution. Recommendations about lifestyle changes to control body weight are generally confined to altering circumstantial factors, whose leverage is weak, compared to that of environmental and genetic influences. Creating opportunities to strive for weight control in group-settings can be advantageous by providing a measure of change in the environment. Similarly, encouraging the acquisition of greater physical activity habits, notably in children and adolescents, offers the potential for 'improving' the environment in population groups.

Alan R. Shuldiner

Professor and Head, Division of Endocrinology, Diabetes, and Nutrition

Director, Joslin Center for Diabetes at the University of Maryland

660 West Redwood St., Room 494

Baltimore, MD 21201

USA

ABSTRACT

The Role of Genes in Obesity

Obesity and susceptibility to its comorbid conditions (e.g., type 2 diabetes, hypertension, hyperlipidemia) are the result of complex interactions between genes and environment (excess caloric intake and physical inactivity). To date mutations in genes (e.g., leptin, leptin receptor, proconvertase-1, pro-opiomelanocortin, PPARgamma, melanocortin-4 receptor) have been found as causes of a few rare monogenic syndromes of obesity in humans. Candidate gene approaches have led to the identification of a few gene variants (e.g., adrenergic receptors, PPARgamma, melanocortin- receptor, uncoupling proteins that are more common in the population, but whose influences on typical forms of obesity are more modest. In recent years, genome-wide approaches using polymorphic markers in families or sibling pairs has provided statistical evidence for the presence of obesity susceptibility genes in several chromosomal regions, including chromosome regions 2p25-21, 7q31 10p15.3-11, 18q21-22, and 20q12-13. This lecture will describe the approaches used to identify obesity susceptibility genes and the progress that has been made to date, including studies of our own in the Old Order Amish of Lancaster County, Pennsylvania, a genetically homogeneous founder population. Steps toward the eventual positional cloning of these putative genes pose a formidable task, but one that is likely to provide key insights into the molecular basis of obesity, which may lead to new prevention and treatment strategies.

Frank Hu

Department of Nutrition

Harvard School of Public Health

665 Huntington Ave.

Boston, MA 02115

USA

ABSTRACT

Diet, Lifestyle, and Obesity.

Diet and lifestyle are primary determinants of overweight and obesity. However, specific dietary and lifestyle risk factors for obesity have not been clearly defined. In a large prospective cohort study of 19,478 men in the Health Professionals' Follow-up Study, we examined the effect of changing common lifestyle habits (exercise, TV viewing, smoking, and eating habits) on 4-year change in body weight (Coakley et al. 1998). We found that for middle-aged men, increasing vigorous exercise was associated with weight reduction, whereas increasing sedentary behavior, indicated by prolonged TV/VCR viewing, was associated with weight gain.. Prolong TV watching was also associated with an unhealthy eating pattern and less physical activity, as well as a significantly increased risk of type 2 diabetes. Eating between meals was associated with weight gain.

Quitting smoking and a history of voluntary weight loss prior to the study were associated with subsequent weight gain. However, recently being on a diet was associated with weight loss. Over the 4-yr follow-up, men who increased their exercise, decreased TV viewing, and stopped eating between meals, lost an average weight of -1.4 kg, compared to a weight gain of 1.4 kg among the overall population. The data suggest that lifestyle modification, particularly increasing physical activity and decreasing sedentary behavior such as TV viewing, has important role in weight maintenance or a modest weight loss over time.

Adam Drewnowski

Director, Nutritional Science Program

School of Public Health and Community Medicine

305 Raitt Hall, No. 353410

University of Washington

Seattle, WA 98195-3410

USA

>ABSTRACT

The Role of Energy Density.

Energy density of foods is a key factor in the regulation of food intake. People tend to consume a fixed amount of food each day rather than a constant amount of energy. According to current theories, high energy density (ED) of the American diet, rather than its fat content, is the main reason for overeating and the growing prevalence of overweight. Selecting lower ED foods in place of high ED foods is said to be a promising approach to weight control.

Initially, ED was equated with the fat content of foods. In reality, ED is almost wholly determined by their water content, with fat playing a lesser role. Raw vegetables and fruit have a naturally low ED because of their high water content (spinach 0.2 kcal/g). Soups, juices and other beverages have an ED in the order of 0.5-1.0 kcal/g. In contrast, dry foods have higher ED values, especially when they contain fat (chocolate 5.4 kcal/g; roasted peanuts 5.8 kcal/g). About 99% of the variance in ED values is accounted for by water and fat.

There are very few studies on the energy density of the total diet. One question is whether non-caloric beverages and water ought to be part of the calculation. Studies suggest that water can have differential effects on satiation when it is consumed as a beverage, as opposed to being incorporated in a soup. Generally, energy density of the typical diet is in the order of 1.0 kcal/g when the calculation includes caloric beverages but excludes non-caloric beverages and water. Excluding all beverages raises energy density to 1.5 kcal/g. Lower ED diets are associated with elevated consumption of vegetables and fruit, whereas higher ED diets are associated with elevated consumption of fast foods and sweet desserts.

Reducing ED of the diet is viewed as a population-based strategy for weight reduction. However, the concept of ED is inextricably linked with two factors that influence food purchases: taste and cost. High ED foods tend to be better-tasting and vice versa. Arguably, foods are good-tasting or palatable precisely because they are energy dense: the physiological pleasure response to energy-dense chocolate is much more powerful than the response to energy-free spinach. Chocolate, which tends to be over-consumed, is by definition less satiating than spinach. As a rule, energy dense foods are palatable but not satiating, whereas low ED foods may be more satiating but are less palatable. Lower ED diets may be less palatable than diets of higher ED and so less appealing to the consumer.

Food costs are a major factor determining food purchases. Dry energy-dense foods are easier to package, distribute, and store than are perishable fresh vegetables and fruit. As a result, high ED foods deliver far more energy per dollar than does fresh produce. Commodity costs of added sugar and added fat are particularly low, such that sucrose at retail can deliver close to 10,000 kcal/dollar. Given that the average US consumer spends approximately $7 per day on foods and beverages combined, and consumes between 2000-2500 kcal/day, the economics of food choice favor low-cost energy-dense foods. Lowering ED of the diet is a proposition that entails economic costs to the consumer.

The current obesity epidemic is mediated by the changing food environment. The question is whether appropriate prevention strategies should emphasize nutrition education and individual choice. There is growing impetus for structural and policy solutions that may involve food price supports, pricing and marketing strategies and the economics of food choice.

David S. Ludwig

Director, Obesity Program

Children's Hospital

300 Longwood Ave.

Boston, MA 02115

USA

ABSTRACT

Role of Macronutrients in Childhood Obesity.

Excessive fat consumption is commonly believed to cause obesity and, for this reason, conventional approaches to weight loss have focused on decreasing dietary fat. However, the relationship between dietary fat and adiposity has been questioned for several reasons. First, weight loss on low-fat diets is characteristically modest in nature. Second, prospective epidemiological studies have not consistently found that individuals eating the most fat are heavier than those eating the least fat. Third, obesity prevalence has risen markedly over the past 3 decades in the US despite a significant decrease in fat consumption as a percent of total energy.

As dietary fat has decreased, carbohydrate consumption has increased in a compensatory fashion, and most of this increase has been in the form of refined starchy food and concentrated sugar. Recent research suggests that increased consumption of these high glycemic index (GI) carbohydrates may have had an unexpected and adverse effect on risk for obesity and related diseases. Short-term feeding studies consistently demonstrate that high GI meals are less satiating than energy- and macronutrient- controlled low GI meals. Several intermediate-term clinical trials found less weight loss among overweight individuals on high compared to low GI diets. One epidemiological analysis demonstrated a direct association between dietary GI and abdominal girth. Animal studies support a role for GI in body weight regulation. Moreover, GI can be related to obesity risk though plausible physiological mechanism. Thus, the effect of macronutrient composition on risk for obesity requires reassessment through physiological investigation and long term clinical trials.

John C. Peters

The Procter & Gamble Company

P.O. Box 538707

Cincinnati, OH 45253-8707

USA

ABSTRACT

Dietary Fat and Body Weight Control: What's the Skinny?

The global obesity epidemic has heightened the debate about dietary factors contribution to weight gain. Media stories have promulgated the notion that obesity has increased despite reductions in dietary fat intake. Some have even speculated that lower dietary fat levels may be driving the rapid rise in weight gain within the population. A close examination of the science reveals a different picture and supports the hypothesis that dietary fat, within the context of the total dietary composition consumed by many populations, promotes obesity. Hence, dietary fat control is still an important strategy as part of an overall approach to body weight management in our modern environment.

Dietary fat increases the energy density of foods. Abundant evidence from preclinical and clinical studies indicates that fat promotes excess energy intake and positive energy balance. Dietary fat does not promote its own oxidation in the body and is efficiently stored, promoting positive fat balance. Thus, both the behavioral and metabolic responses to dietary fat increase the probability of positive energy balance and body fat gain. Restoring fat balance on diets rich in fat requires increasing the size of the body fat mass, increasing physical activity or reducing dietary fat intake.

Numerous epidemiological, preclinical and controlled clinical studies show that body fat is positively associated with dietary fat intake and that dietary fat manipulation leads to appropriate changes in body fat mass. Finally, data from the National Weight Control Registry, a database of over 3000 individuals that have successfully maintained a substantial weight loss, indicate that moderating dietary fat intake is a key strategy for long-term management of body weight.

Brent D. Flickinger

Archer Daniels Midland Company

Randall Research Center

1001 N. Brush College Rd.

Decatur, IL 62521-1656

USA

ABSTRACT

Nutritional Functions of Dietary Diacylglycerol.

Diacylglycerol (DAG) oil is an edible oil containing 80% or greater amount of DAG with natural fatty acids, 70% of which is in the 1,3-DAG isoform, and its energy value and digestibility are practically the same as ordinary oil containing triacylglycerol (TAG). The nutritional function of DAG has been studied in both single loading and long-term ingestion.

In humans, postprandial elevations of triglyceride in chylomicron are markedly smaller after consumption of oil emulsions containing DAG compared to that containing TAG with a similar fatty acid composition. Moreover, the postprandial increase of remnant lipoprotein lipids, which are stronger risk factors in cardiovascular heart diseases, were less after ingestion of the DAG emulsion than after the TAG emulsion.

Long-term DAG consumption (16 wks) prevented the accumulation of body fat and body weight in Japanese men (n=38) in a double blind controlled study with unrestricted carbohydrate energy intake. DAG has also been shown to enhance reductions in body weight and fat mass when incorporated into a hypocaloric diet in a randomized, double-blind, parallel study using overweight or obese Americans (n=127). In this study, 15% of energy were taken from test oils in hypocaloric diet (500-800 kcal/d deficit) containing either DAG or TAG oil for 24 wks.

From the results of these studies, it has been concluded that foods containing DAG oil promoted weight loss and body fat reduction and may thus be useful as an adjunct to diet therapy in the management of obesity.

To gain insight into the mechanism of these DAG functions, we studied the effects of substituting DAG for TAG in high fat (30%) plus sucrose (13%) diet in obesity- and diabetes-prone mice C57BL/6J. After five months of ad libitum feeding, high fat induced elevation of body weight and fat were significantly suppressed by substituting DAG for TAG. Hepatic acyl-coenzyme A oxidase activity and mRNA for acyl-coenzyme A synthase were increased, suggesting a higher capacity for hepatic lipid oxidation. Total daily energy intake and fecal fat loss did not differ between the two high-fat treatments. These results suggested that DAG consumption produced an increase in energy expenditure.

We are further investigating the mechanism of dietary DAG function in both animals and humans.

Bengt Vessby

Unit for Clinical Nutrition Research

Dept. of Public Health and Caring Sciences

University of Uppsala

P.O. Box 609

SE-751 25 Uppsala

Sweden

ABSTRACT

Conjugated linoleic acid (CLA) and body weight regulation in humans.

B. Vessby, U. Risérus, A. Smedman and S. Basu.

Unit for Clinical Nutrition Research, Dept of Public Health and Caring Sciences, University of Uppsala, P.O.Box 609, SE-75125 Uppsala, Sweden

Conjugated linoleic acid (CLA) comprises a group of unsaturated fatty acid isomers with a variety of biological effects in experimental animal studies. CLA reduces body fat accumulation and has been ascribed significant effects on lipid and glucose metabolism, e.g. antidiabetic effects in obese Zucker rats. It has been suggested that the t10c12 CLA isomer is the active isomer as regards antiobesity and insulin sensitizing properties of CLA. The metabolic effects of CLA in humans in general, and isomer specific effects specifically, are not well characterized. We have in a series of controlled studies in humans investigated the effects of CLA (given as the commercially available mixture of isomers) and of the purified t10c12 isomer on anthropometry, lipid and glucose metabolism, on markers of lipid peroxidation and on endocrine and proinflammatory factors. Preliminary results indicate that CLA may slightly decrease body fat also in humans, particularly abdominal fat, but there is no simultaneous improvement of lipid or glucose metabolism. Rather, the t10c12 isomer unexpectedly caused significant impairment of the peripheral insulin sensitivity as well as of blood glucose and serum lipid levels. In addition, CLA markedly elevated lipid peroxidation. Thus, the metabolic effects of CLA in humans seem complex and further studies, especially of isomer specific effects, are needed.

Michael B. Zemel

Head, Department of Nutrition

The University of Tennessee

1215 W. Cumberland Ave.

Room 229

Knoxville, TN 37996

USA

ABSTRACT

The Metabolic Shift: Calcium, Dairy Products, and Weight Control.

Dietary calcium plays a pivotal role in the regulation of energy metabolism, as we have found high calcium diets to attenuate adipocyte lipid accretion and weight gain during periods of over-consumption of an energy-dense diet and to increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Our studies of the agouti gene in obesity and insulin resistance demonstrate a key role for intracellular Ca²⁺ in regulating adipocyte lipid metabolism and triglyceride storage, with increased intracellular Ca²⁺ resulting in stimulation of lipogenic gene expression and lipogenesis and suppression of lipolysis, resulting in adipocyte lipid filling and increased adiposity. Moreover, we have recently demonstrated that the increased calcitriol produced in response to low calcium diets stimulate Ca²⁺ influx in human adipocytes and thereby promote adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for the prevention and management of obesity. In support of this concept, transgenic mice expressing the agoutigene specifically in adipocytes (a human-like pattern) respond to low calcium diets with accelerated weight gain and fat accretion, while high calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low calcium diets impede body fat loss, while high calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. Notably, dairy sources of calcium exert markedly greater effects in attenuating weight and fat gain and accelerating fat loss. This augmented effect of dairy versus supplemental calcium is likely due to additional bioactive compounds in dairy which act synergistically with calcium to attenuate adiposity; among these are angiotensin converting enzyme inhibitory peptides which limit angiotensin II production and thereby limit angiotensin II stimulation of adipocyte lipogenesis. These concepts are confirmed by both epidemiological and clinical data which demonstrates that increasing dietary calcium results in significant reductions in adipose tissue mass in obese humans in the absence of caloric restriction and markedly accelerates the weight and body fat loss secondary to caloric restriction. Moreover, dairy products exert a substantially greater effect on both fat loss and fat distribution, with significantly greater amounts of fat loss from the trunk region on high dairy diets, compared to an equivalent amount of supplemental calcium. These data indicate an important role for dairy products in both the prevention and treatment of obesity.

David B. Allison

Department of Biostatistics, Ryals

Health Building, Building 327

1665 University Blvd.

University of Alabama at Birmingham

UAB Station

Birmingham, AL 35294-0022

USA

ABSTRACT

Approaches to Treating and Preventing Obesity: What Does, Doesn't, and Might Work.

Obesity is increasing in prevalence and appears to be causally related to impaired quality of life, a number of serious health impairments, and earlier death. Thus, concerted efforts to develop, refine, and evaluate methods to effectively treat and prevent obesity are in order. In this paper data addressing the question of whether we can reasonably expect weight loss treatment to improve health and increase longevity will be reviewed. This will be followed by a review of data on the clinical treatment of obesity including behavioral, pharmacological, and surgical methods. Subsequently, available evidence on population, community, and school-based approaches to preventing obesity will be critically examined. Finally, some speculative comments on what future approaches are likely to be most and least effective and suggestions for future research will be offered.

Van S. Hubbard

Director

NIH Division of Nutrition Research Coordination

6707 Democracy Boulevard

MSC 5450, Room 631

Bethesda, MD 20892

USA

ABSTRACT

National Actions Addressing the Obesity Epidemic.

A major national prevention initiative is encompassed within Healthy People, a program developed by the US Department of Health and Human Services for the promotion of health and disease prevention objectives. Healthy People 2010 launched in January 2000 seeks to have increased involvement at the state and community level. Healthy People 2010 also will be considered as part of our Nation's effort to adopt the World Health Organization's "Health for All" strategy and thus contribute a potential model for world policy and strategies for population health improvement. Stemming the tide of the increasing prevalence of overweight (BMI > 25) and obesity (BMI > 30) in adults and a BMI equal or greater than the 95^th percentile derived from the revised growth curves in youth, and encouraging people to move toward a healthier weight are major public health goals. The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity was released in December 2001. The purpose of the Call to Action is to alert the American public to the critical nature of the epidemic of overweight and obesity and to mobilize national collaborative efforts to address it. The document emphasizes the impact of overweight and obesity on health and identifies several critical priorities for action. It summarizes actions called for by the public at the May 2000 National Nutrition Summit, the December 2000 Surgeon General=s Listening Session on Overweight and Obesity and suggests the creation of public/private working groups that could be formed around key themes or the major settings in which obesity prevention and treatment efforts need to take place. Consistent objectives of all of these activities include the heightening of awareness by the public and the health care provider of factors associated with the development of overweight and obesity, the relative health consequences of increased body weight, and appropriate considerations for prevention or intervention. The health consequences of increased body weight are part of a continuum. Numerous studies have noted the disparities in prevalence of overweight and obesity among populations of different ethnic origin. Similarly, there are marked differences in the health risk at a given BMI, especially within certain ethnic groups. The challenge is to develop appropriate health messages and interactions with our academic and public health colleagues, industry, the public and the media to convey the concepts relating to weight, weight management, and health risks associated with various degrees being overweight or obese.

Sylvia Rowe

President and CEO

International Food Information Council

1100 Connecticut Ave., NW, 430

Washington, DC 20036 USA

ABSTRACT

Consumer Knowledge, Attitudes, and Practices on Diet and Weight Control.

Overweight and obesity are growing epidemics. With an increase of 50 percent since 1991 among children who are overweight or at risk for overweight, the trend is particularly alarming. The media increasingly covers the issue, frequently offering simple solutions to this pressing issue. Diet, and specifically intake of dietary fat, is often singularly blamed for overweight. At other times, sugars; portion size; lack of physical education; too much TV; automobiles; genetics; community design and other factors are blamed.

In reality, ongoing research, review, and debate generate novel ideas and provide new insights to current scientific and cultural understanding of overweight and obesity, just as with other science and public health issues. However, health information is frequently reported to the public without context, which creates confusion. One study seemingly contradicts another, leaving consumers to doubt science, scientific experts, and health advice.

This presentation will highlight consumer research to illustrate consumer confusion, frustration, and apathy toward nutrition science and how consumer attitudes toward dietary fat may have shifted in recent years. In-depth research--focus groups, in-home observations, one-on-one interviews and quantitative--showing consumer attitudes specifically on overweight and obesity will also be shared.

Ultimately, the presentation will show how science communications and health advice can be tailored for specific audiences, and, importantly, how scientists themselves can help the media understand and position research in order to minimize consumer confusion.