Obesity: Basic metabolic principles

Obesity

Basic metabolic principles

Obesity is the most common form of a disruption in energy balance and now constitutes one of the major and most prevalent disorders of nutrition. Because of the strong relationship between obesity and health risks, obesity is now generally considered a disease by health professionals.

Although the body continuously consumes a mixed diet of carbohydrate, protein, and fat, and sometimes alcohol, the preferred store of energy is fat. There is a clearly defined hierarchy of energy stores that out-lines a preferential storage of excess calories as fat. For alcohol, there is no storage capacity in the body. Thus, alcohol that is consumed is immediately oxidized for energy. For protein, there is a very limited storage capacity and, under most situations, protein metabo-lism is very well regulated. For carbohydrate there is only a very limited storage capacity, in the form of glycogen, which can be found in the liver and in muscle. Glycogen provides a very small and short-term energy store, which can easily be depleted after an overnight fast or after a bout of exercise. Most carbohydrate that is consumed is immediately used for energy. Contrary to popular belief, humans cannot convert excess carbohydrate intake to fat. Instead, when excess carbohydrates are consumed, the body adapts by preferentially increasing its use of carbohy-drate as a fuel, thus, in effect, burning off any excessive carbohydrate consumption. Large excesses of carbohydrate may induce de novolipogenesis, but normally this process is quantitatively minor. However, no such adaptive mechanism for fat exists. In other words, if excess fat is consumed, there is no mechanism by which the body can increase its use of fat as a fuel. Instead, when excess fat calories are con-sumed, the only option is to accumulate the excess fat as an energy store in the body. This process occurs at a very low metabolic cost and is therefore an extremely efficient process. To store excess carbohydrate as glycogen is much more metabolically expensive and therefore a less efficient option. There is another important reason why the body would prefer to store fat rather than glycogen. Glycogen can only be stored in a hydrated form that requires 3 g of water for each gram of glycogen, whereas fat does not require any such process. In other words, for each gram of glyco-gen that is stored, the body has to store an additional 3 g of water. Thus, for each 4 g of storage tissue, the body stores only 16.8 kJ, equivalent to just 4.2 kJ/g, compared with the benefit of fat which can be stored as 37.8 kJ/g.

Thus, a typical adult with 15 kg of fat carries 567.0 MJ of stored energy. If the adult did not eat and was inactive, he or she might require 8.4 MJ/day for survival, and the energy stores would be sufficient for almost 70 days. This length is about the limit of human survival without food. Given that glycogen stores require 4 g to store 4.2 kJ (3 g of water plus 1 g of gly-cogen = 16.8 kJ), we can calculate that to carry this much energy in the form of glycogen requires 135 kg of weight. It is no wonder therefore that the body’s metabolism favors fat as the preferred energy store.

Definition of obesity

Obesity has traditionally been defined as an excess accumulation of body energy, in the form of fat or adipose tissue. Thus, obesity is a disease of positive energy balance, which arises as a result of dysregula tion in the energy balance system – a failure of the regulatory systems to make appropriate adjustments between intake and expenditure. It is now becoming clear that the increased health risks of obesity may be conferred by the distribution of body fat. In addition, the influence of altered body fat and/or body fat dis-tribution on health risk may vary across individuals. Thus, obesity is best defined by indices of body fat accumulation, body fat pattern, and alterations in health risk profile.

The body mass index (BMI) is now the most accepted and most widely used crude index of obesity. This index classifies weight relative to height squared. The BMI is therefore calculated as weight in kilo-grams divided by height squared in meters, and expressed in the units of kg/m2. Obesity in adults is defined as a BMI above 30.0 kg/m2, while the normal range for BMI in adults is 18.5–24.9 kg/m2. A BMI in the range of 25–30 kg/m2 is considered overweight. In children, it is more difficult to classify obesity by BMI because height varies with age during growth; thus, age-adjusted BMI percentiles must be used.

One of the major disadvantages of using the BMI to classify obesity is that this index does not distin-guish between excess muscle weight and excess fat weight. Thus, although BMI is strongly related to body fatness, at any given BMI in a population, there may be large differences in the range of body fatness. A classic example of misclassification that may arise from the use of the BMI is a heavy football player or body-builder with a large muscle mass who may have a BMI above 30 kg/m2 but is not obese; rather, this man has a high body weight for his height resulting from increased FFM.

Since the health risks of obesity are related to body fat distribution, and in particular to excess abdominal fat, other anthropometric indices of body shape are useful in the definition of obesity. Traditionally, the waist-to-hip ratio has been used as a marker of upper versus lower body-fat distribution. More recent studies suggest that waist circumference alone pro-vides the best index of central body-fat pattern and increased risk of obesity-related conditions. The rec-ommended location for the measurement of waist circumference is at the midpoint between the lowest point of the rib cage and the iliac crest. The risk of obesity-related diseases is increased above a waist cir-cumference of 94 cm in men and above 80 cm in women.

Etiology of obesity: excess intake or decreased physical activity

Stated simply, obesity is the end-result of positive energy balance, or an increased energy intake relative to expenditure. It is often stated, or assumed, that obesity is simply the result of overeating or lack of physical activity. However, the etiology of obesity is not as simple as this, and many complex and interre-lated factors are likely to contribute to the develop-ment of obesity; it is extremely unlikely that any single factor causes obesity. Many cultural, behav-ioral, and biological factors drive energy intake and energy expenditure, and contribute to the homeo-static regulation of body energy stores, as discussed earlier. In addition, many of these factors are influenced by individual susceptibility, which may be driven by genetic, cultural, and hor-monal factors. Obesity may develop very gradually over time, such that the actual energy imbalance is negligible and undetectable.

Although there are genetic influences on the various components of body-weight regulation, and a major portion of individual differences in body weight can be explained by genetic differences, it seems unlikely that the increased global prevalence of obesity has been driven by a dramatic change in the gene pool. It is more likely and more reasonable that acute changes in behavior and environment have contributed to the rapid increase in obesity, and genetic factors may be important in the differing individual susceptibilities to these changes. The most striking behavioral changes that have occurred have been an increased reliance on high-fat and energy-dense fast foods, with larger portion sizes, coupled with an ever-increasing seden-tary lifestyle. The more sedentary lifestyle is due to an increased reliance on technology and labor-saving devices, which has reduced the need for physical activ-ity for everyday activities. Examples of energy-saving devices are:

●      increased use of automated transport rather than walking or cycling

●      central heating and the use of automated equip-ment in the household, e.g., washing machines

●      reduction in physical activity in the workplace due to computers, automated equipment, and elec-tronic mail, which all reduce the requirement for physical activity at work

●increased use of television and computers for enter-tainment and leisure activities

●use of elevators and escalators rather than using stairs

●increased fear of crime, which has reduced the like-lihood of playing outdoors

●poor urban planning, which does not provide adequate cycle lanes or even pavements in some communities.

Thus, the increasing prevalence, numerous health risks, and astounding economic costs of obesity clearly justify widespread efforts towards prevention.

The relationship between obesity and lifestyle factors reflects the principle of energy balance. Weight maintenance is the result of equivalent levels of energy intake and energy expenditure. Thus, a discrepancy between energy expenditure and energy intake de-pends on either food intake or energy expenditure, and it is becoming clear that physical activity provides the main source of plasticity in energy expenditure. In addition, lifestyle factors such as dietary and activ-ity patterns are clearly susceptible to behavioral mod-ification and are likely targets for obesity prevention programs. A second, yet related, reason that control of the obesity epidemic will depend on preventive action is that both the causes and health consequences of obesity begin early in life and track into adulthood. For example, both dietary and activity patterns responsible for the increasing prevalence of obesity are evident in childhood.

Role of physical activity and energy expenditure in the development of obesity

Although it is a popular belief that reduced levels of energy expenditure and physical activity lead to the development of obesity, this hypothesis remains con-troversial and has been difficult to prove. There are certainly good examples of an inverse relationship between physical activity and obesity (e.g., athletes are lean and nonobese individuals), as well as good examples of the positive relationship between obesity and physical inactivity (obese individuals tend to be less physically active). However, not all studies provide supporting evidence. For example, several studies suggest that increased television viewing (as a marker for inactivity) increases the risk of obesity, whereas others do not. Similar to the results for physical active ity, some studies suggest that a low level of energy expenditure predicts the development of obesity, and others do not support this hypothesis.

Physical activity is hypothesized to protect people from the development of obesity through several channels. First, physical activity, by definition, results in an increase in energy expenditure owing to the cost of the activity itself, and is also hypothesized to increase RMR. These increases in energy expenditure are likely to decrease the likelihood of positive energy balance. However, the entire picture of energy balance must be considered, particularly the possibility that increases in one or more components of energy expenditure can result in a compensatory reduction in other components (i.e., resting energy expenditure and activity energy expenditure). Secondly, physical activity has beneficial effects on substrate metabo-lism, with an increased reliance on fat relative to carbohydrate for fuel utilization, and it has been hypothesized that highly active individuals can main-tain energy balance on a high-fat diet.

Cross-sectional studies in children and adults have shown that energy expenditure, including physical activity energy expenditure, is similar in lean and obese subjects, especially after controlling for differ-ences in body composition. Children of obese and lean parents have also been compared as a model of preobesity. Some studies show that children of obese parents had a reduced energy expenditure, including physical activity energy expenditure, whereas another study did not. A major limitation of the majority of studies that have examined the role of energy expen-diture in the etiology of obesity is their cross-sectional design. Because growth of individual components of body composition is likely to be a continuous process, longitudinal studies are necessary to evaluate the rate of body fat change during the growing process. Again, some longitudinal studies support the idea that reduced energy expenditure is a risk factor for the development of obesity, whereas others do not. Finally, intervention studies have been conducted to determine whether the addition of physical activity can reduce obesity. These studies tend to support the positive role of physical activity in reducing body fat.

Several possibilities could account for such dis-crepant findings. First, the ambiguous findings in the literature may be explained by the possibility that differences in energy expenditure and physical activ-ity and their impact on the development of obesity are different at the various stages of maturation. This hypothesis is supported by previous longitudinal studies in children, showing that a reduced energy expenditure is shown to be a risk factor for weight gain in the first 3 months of life, but not during the steady period of prepubertal growth. Secondly, there could be individual differences in the effect of altered energy expenditure on the regulation of energy balance. Thus, the effect of energy expenditure on the etiology of obesity could vary among different sub-groups of the population (e.g., boys versus girls, dif-ferent ethnic groups) and could also have a differential effect within individuals at different stages of devel-opment. It is conceivable that susceptible individuals fail to compensate for periodic fluctuations in energy expenditure. Third, explanations related to the meth-odology can also be offered because of the complexity of the nature of physical activity and its measure-ment. The success of controlled exercise interven-tions in improving body composition indicates an extremely promising area for the prevention of obesity. However, further studies are required to elu-cidate the specific effects of different types of exercise on the key features of body weight regulation.