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PART 1
The Biology of ObesityâWhy It Occurs
Victor Lawrence, Section Editor
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CHAPTER 1
Energy Balance and Body Weight Homeostasis
Key points
- Energy intake is highly variable, and mechanisms to defend a âset pointâ in energy stores appear to have evolved.
- Energy is spent doing useful physical, chemical, and electrical work and also producing heat (thermogenesis) as a by-product of these activities.
- Thermogenesis is subject to regulation and may be adapted to prevailing energy balance.
- Basal metabolic rate (BMR) increases predominantly in proportion to lean body mass and is higher in the obese. Its fall with caloric restriction may present a barrier to long-term weight loss.
- Energy is also spent in voluntary (exercise) and other non-exercise activity Âthermogenesis (NEAT).
- Spontaneous physical activity (SPA) is a major component of NEAT and is regulated by the sympathetic nervous system (SNS), and its fall with caloric restriction may present a barrier to successful weight loss.
- Genetic and acquired variations in the amount and efficiency of these largely unconscious processes may explain some inter- and intra-individual variability in energy metabolism and thus predisposition toward obesity.
- Food (energy) intake is subject to complex regulation by circulating and gut-derived signals which include leptin.
- In addition to its effects on energy intake, leptin has the ability to stimulate adaptive thermogenesis via SPA, uncoupling of oxidative phosphorylation, and possibly via futile cycling. Many of these effects depend on the SNS.
- Leptin deficiency or receptor mutations are a very rare cause of human obesity. Nevertheless, relative defects in leptin action may (at least in theory) influence body weight homeostasis and are the subject of current research.
- Brown adipose tissue (BAT) exists in adults; it is regulated by the SNS and contributes to thermogenesis. Stimulating its differentiation and activation is a target of current research.
CASE STUDIES
Case study 1
CF is a 24-year-old woman with a body mass index (BMI) of 32 kg/m2. She describes an apparently healthy diet which she considers to be no higher in calories than that taken by many of her friends and family who do not have weight problems. She also walks regularly. She feels immensely frustrated over her seeming inability to achieve or maintain an ideal body weight despite good habits and is starting to feel like giving up.
Comment: You explore her concerns and find that she is certain that she has an undiagnosed metabolic problem leading to a slow metabolism, a problem she feels runs in her family despite repeatedly normal tests of thyroid function. You explain that the body does adapt over time to a change in weight and the new higher or lower weight tends to be opposed by changes in metabolic rate and overall energy expenditure which can make the achievement and maintenance of weight loss progressively harder. You arrange to measure her resting metabolic rate principally to demonstrate to her that it lies in the range expected for body composition, age, and sex. You explain how SPA may lessen over time in people who are losing weight and discuss ways of maintaining this, for example, walking to the shops, taking stairs rather than escalators, and measuring the number of daily footsteps with a pedometer. You also explain that periods of weight maintenance are perfectly logical (and successful) as part of a long-term program of weight control and may permit the body to acclimatize and form a new set pointâthe only outcome that represents failure is to give up and regain any weight lost. She finds sufficient motivation in these concepts to re-energize herself in her weight loss goals.
Case study 2
LW, an obese 58-year-old man, has been very gradually but successfully reducing his weight with your support over the past year. However, his weight loss trajectory has stopped over the past month and he has begun to regain weight.
Comment: You enquire about changes in his circumstances and discover that his primary care physician recently started him on a beta-blocker following possible, although incompletely ascertained, intolerance of first-line drug therapy for his hypertension. You explain that beta-blockers inhibit the actions of the SNS. This could affect his overall energy balance in several ways, including reduced lipolysis (and possibly therefore reduced futile cycling of fatty acids between free and esterified forms) and reductions in thermogenesis, SPA, and in overall metabolic rate. Furthermore, beta-blockers may also reduce exercise capacity and cause fatigue, all of which may counter attempted weight loss. Although the magnitude of these effects is small (typically 1â2 kg, 2.2â4.4 lb), it is possible that some individuals may be affected more than this. Older ânon-selectiveâ beta-blockers appear to be more problematic than newer âcardioselectiveâ agents. On discussing this, together with possible adverse effects on insulin sensitivity, you agree to try an angiotensin receptor blocking agent.
Introduction
In most individuals, body weight remains relatively stable over years to decades despite wide variations in energy intake and expenditure. This would seem to suggest that body weight is rigorously defended by Âhomeostatic mechanisms. However, whilst a useful defense against the development of obesity, any tendency to defend a set point once obesity is established may act as a barrier to the achievement and maintenance of planned weight loss.
Many individuals seeking professional help in relation to their own obesity become confused or frustrated by what appears to be inability to lose weight (or a tendency to gain weight) despite behaviors that might appear no less healthy than other individuals who do not appear to have a weight problem. Some will have developed counterproductive health beliefs that may act as barriers to weight loss (e.g., that they must have a slow metaÂbolism and that this is genetically programmed or is the result of some Âundiagnosed metabolic disorder and therefore beyond their control). These misunderstandings can rapidly evolve into a sense of âlearned helplessnessâ and all too often result in disengagement and failure to achieve goals.
Clear and accurate explanations of the complexities of energy balance regulation are often of practical help, particularly where such frustration or despondency exists.
Basic concepts and principles in human energetics
Energy balance and laws of thermodynamics
According to the first law of thermodynamics,
The chemical energy obtained from food is used to perform a variety of work, such as
- synthesis of new macromolecules (chemical work)
- muscular contraction (mechanical work)
- maintenance of ionic gradients across membranes (electrical work)
Thus, if the total energy contained in the body (in the form of fat, protein, and glycogen) of a given individual is not altered (i.e., Î energy stores = 0), then energy expenditure must be equal to energy intake and the individual is said to be in a state of energy balance.
If the intake and expenditure of energy are not equal, then a change in body energy content will occur, with negative energy balance resulting in the degradation of the bodyâs energy stores (glycogen, fat, and protein) or positive energy balance resulting in an increase in body energy stores, primarily as fat.
The second law of thermodynamics makes a distinction between the potential energy of food, useful work, and heat. It states essentially that
and describes the fact that when food is utilized in the body, these processes must be accompanied inevitably by some loss of heat. In other words, the conversion of available food energy is not a perfectly efficient process: about 75% of the chemical energy contained in foods may be ultimately dissipated as heat because of the inefficiency of intermediary metabolism. The energy âwastedâ as heat may be calculated as the sum of BMR and adaptive thermogenesis. Adaptive thermogenesis refers to the increase in resting energy expenditure in response to stimuli such as food intake, cold, stress, and drugs.
Components of energy expenditure
It is customary to consider human energy expenditure as being made up of three components:
- Energy spent on basal metabolism (BMR)
- Energy spent on physical activity (work done plus exercise- or Ânon-exercise-associated thermogenesis)
- The increase in resting energy expenditure in response to stimuli such as food, cold, stress, and drugs (adaptive thermogenesis).
These three components are depicted in Figure 1.1 and are described in the following text.
Basal (or resting) metabolic rate (BMR)
This is the largest component of energy expenditure for most individuals. Typically, BMR accounts for 60...
