In spite of great fluctuation in the quantity and frequency of eating, we all maintain remarkable precision between energy expenditure and energy intake. Social factors, emotions, and time of day, as well as taste, satiety, and personal habits, influence our eating patterns, yet we maintain a reasonably stable body weight month after month. This is referred to as energy homeostasis or simply a metabolic “set point.”

Evidence of a set point comes from a variety of sources. If a rat is deprived of food, then, when offered a normal diet, it will overeat for a short period and return its body weight to its preexisting level. Likewise, after being force-fed to increase body weight, it will limit its food intake to return to normal weight (Figure 13.1). The brain and body work in harmony to keep the body weight at a specific point.

The human corollary to this is the disturbingly low success rates that people have with most diets. In a review of long-term efficacy of dietary treatment interventions for obesity, Ayyad and Anderson found that only 15% of the patients fulfilled at least one of the criteria for success 5 years after the study. Unfortunately, most people who diet will slowly return to their preexisting weight within 1 year.

Several lines of research suggest that the set point is genetically controlled. Adoption studies provide a unique way to separate the effects of genetics from environment on body weight by comparing children with their biologic parents and with the parents from the house in which they were raised. In an analysis of Danish adoptees, Stunkard et al. found a strong relation between weight class of the adoptees and the body mass of the biologic parents. However, there was no correlation between the weight class of the adoptees and their adopted parents, suggesting that genetic makeup, not environment, is a major determining factor in one’s body weight.

Yet, obesity was a rare condition 50 years ago. Clearly, our genes have not evolved in half a century. There must be other explanations for the significant change in body weight that is occurring in first-world nations. The Pima Indians of Mexico and Arizona can provide some insight on this issue.

The Pima Indians separated into two tribes approximately 700 to 1,000 years ago—one tribe remained in Mexico and the other settled in what is now known as Arizona. In spite of their similar genetic makeup, they have remarkably different average body weights. The Arizona Indians have a high prevalence of obesity and non-insulin-dependent diabetes mellitus, whereas their Mexican relatives are not overweight and have little diabetes. The difference can be best explained by understanding the divergent lifestyles these two populations developed.

The Mexican Pima Indians have remained in the mountains, continuing a traditional rural lifestyle. They exert considerable physical energy working the farms and eat a diet high in starch and fiber. The Arizona Indians, on the other hand, were forced to move onto reservations and abandon their former way of life. There they lead more leisurely lives and eat a diet high in fat and sugar.

The obesity problem that the Pima Indians suffer from has been attributed to a “thrifty gene”—a gene that promotes saving and storing calories. Two thousand years ago, such a genetic predisposition would enhance the survival for those struggling with the fluctuations of prosperity and famine. However, with plentiful high caloric, highly palatable food, the “thrifty gene” promotes accumulation and storage beyond what is healthy. So the weight problem is genetic, but influenced by what is available in the environment.

The concept of a set point helps us understand the difficulties encountered by anyone trying to diet. One of the mechanisms the brain uses to return the body weight to its baseline set point became apparent in the Minnesota Starvation Experiment. This was an experiment conducted with conscientious objectors in Minnesota toward the end of the Second World War to help the military understand the condition of the starving civilians in Europe.

Participants were subjected to a semistarvation diet for 6 months with the goal of losing approximately 25% of their weight. From our perspective, one of the more interesting symptoms these men experienced during the experiment was obsessive thought about food. Not unlike the cravings discussed in the previous chapter, food became the principal topic of their thoughts, conversation, and daydreams. Reading cookbooks and collecting recipes became an intensely interesting pastime for many men. Eating, either mentioned in a book or shown in a movie, was a cue that put the men at heightened risk for breaking their diet. The urge to eat was so powerful that the researchers established a buddy system so that participants would not be tempted to cheat when away from the dorm. Clearly, their brains were focusing on what the body needed.

The brain can also adjust the energy expenditure as another way to maintain a stable body weight. Figure 13.2 shows a thermodynamic perspective of energy expenditure. Energy enters an organism as food and exits as heat or work. Energy is stored as fat or glycogen and mobilized when needed. Total energy expenditure can be subdivided into three components: obligatory energy expenditure, physical activity, and adaptive thermogenesis.

Adaptive thermogenesis is the other major obstacle the brain uses to thwart weight loss. Changes in sympathetic tone alter energy expenditure. For example, activation of the sympathetic nervous system results in catabolic breakdown of adipose tissue and produces energy. Figure 13.3 shows the changes in energy expenditure in healthy subjects after a 10% alteration in body weight. Not only does the brain increase adaptive thermogenesis when the body gains weight but also turns it down in response to weight loss—a frustration many dieters have experienced.

The key point is that despite large day-to-day fluctuations in food intake and energy expenditure, our weight remains within a relatively narrow range.
This is accomplished through feedback loops between the brain and the body. Brain lesion and stimulation studies in the 1940s identified the hypothalamus as a major center controlling food intake. Although the initial studies turned out to be overly simplified, the hypothalamus remains an important command center for weight maintenance.

But what are the signals the brain receives and sends? Interrupting or enhancing these signals may provide opportunities for interventions to stem the obesity epidemic. The best way to understand the current conceptualization of the central nervous system (CNS) homeostatic mechanisms is to separate the short-term signals from the long-term ones.