in total energy expenditure, we have more energy, more body heat and we feel great. After the period of forced overeating, the increased metabolism quickly sheds the excess pounds of fat. The increase in nonexercise activity thermogenesis may account for up to 70 percent of the increased energy expenditure.5
The results described above are by no means isolated findings. Virtually all overeating studies have produced the same result.6 In a 1992 study, subjects were overfed calories by 50 percent over six weeks. Body weight and fat mass did transiently increase. Average total energy expenditure increased by more than 10 percent in an effort to burn off the excess calories. After the forced overfeeding period, body weight returned to normal and total energy expenditure decreased back to its baseline.
The paper concluded “that there was evidence that a physiological sensor was sensitive to the fact that body weight had been perturbed and was attempting to reset it.”
More recently, Dr. Fredrik Nystrom experimentally overfed subjects double their usual daily calories on a fast-food diet.7 On average, weight and body mass index increased 9 percent, and body fat increased 18 percent—by itself, no surprise. But what happened to total energy expenditure? Calories expended per day increased by 12 percent. Even when ingesting some of the most fattening foods in the world, the body still responds to the increased caloric load by trying to burn it off.
The theory of obesity that’s been dominant for the last half century—that excess calories inevitably lead to obesity—the theory that’s assumed to be unassailably true, was simply not true. None of it was true.
And if excess calories don’t cause weight gain, then reducing calories won’t cause weight loss.
THE BODY SET WEIGHT
YOU CAN TEMPORARILY force your body weight higher than your body wants it to be by consuming excess calories. Over time, the resulting higher metabolism will reduce your weight back to normal. Similarly, you can temporarily force your body weight lower than your body wants it to be by reducing calories. Over time, the resulting lowered metabolism will raise your weight back to normal.
Since losing weight reduces total energy expenditure, many obese people assume that they have a slow metabolism, but the opposite has proved to be true.8 Lean subjects had a mean total energy expenditure of 2404 calories, while the obese had a mean total energy expenditure of 3244 calories, despite spending less time exercising. The obese body was not trying to gain weight. It was trying to lose it by burning off the excess energy. So then, why are the obese . . . obese?
The fundamental biological principle at work here is homeostasis. There appears to be a “set point” for body weight and fatness, as first proposed in 1984 by Keesey and Corbett.9 Homeostatic mechanisms defend this body set weight against changes, both up and down. If weight drops below body set weight, compensatory mechanisms activate to raise it. If weight goes above body set weight, compensatory mechanisms activate to lower it.
The problem in obesity is that the set point is too high.
Let’s take an example. Suppose our body set weight is 200 pounds (approximately 90 kilograms). By restricting calories, we will briefly lose weight—say down to 180 pounds (approximately 81 kilograms). If the body set weight stays at 200 pounds, the body will try to regain the lost weight by stimulating appetite. Ghrelin is increased, and the satiety hormones (amylin, peptide YY and cholecystokinin) are suppressed. At the same time, the body will decrease its total energy expenditure. Metabolism begins shutting down. Body temperature drops, heart rate drops, blood pressure drops and heart volume decreases, all in a desperate effort to conserve energy. We feel hungry, cold and tired—a scenario familiar to dieters.
Unfortunately, the result is the regain of weight back to the original body set weight of 200 pounds. This outcome, too, is familiar to dieters. Eating more is not the cause of weight gain but instead the consequence. Eating more does not make us fat. Getting fat makes us eat more. Overeating was not a personal choice. It is a hormonally driven behavior—a natural consequence of increased hunger hormones. The question, then, is what makes us fat in the first place. In other words, why is the body set weight so high?
The body set weight also works in the reverse. If we overeat, we will briefly gain weight—say to 220 pounds (approximately 100 kilograms). If the body set weight stays at 200 pounds, then the body activates mechanisms to lose weight. Appetite decreases. Metabolism increases, trying to burn off the excess calories. The result is weight loss.
Our body is not a simple scale balancing Calories In and Calories Out. Rather, our body is a thermostat. The set point for weight—the body set weight—is vigorously defended against both increase and decrease. Dr. Rudolph Leibel elegantly proved this concept in 1995.10 Subjects were deliberately overfed or underfed to reach the desired weight gain or loss. First, the group was overfed in order to gain 10 percent of their body weight. Then, their diet was adjusted to return them to their initial weight, and then a further 10 percent or 20 percent weight loss was achieved. Energy expenditure was measured under all of these conditions.
As subjects’ body weight increased by 10 percent, their daily energy expenditure increased by almost 500 calories. As expected, the body responded to the intake of excess calories by trying to burn them off. As weight returned to normal, the total energy expenditure also returned to baseline. As the group lost 10 percent and 20 percent of their weight, their bodies reduced their daily total energy expenditure by approximately 300 calories. Underfeeding did not result in the weight loss expected because the total energy expenditure decreased to counter it. Leibel’s study was revolutionary because it forced a paradigm shift in our understanding of obesity.
No wonder it is so hard to keep the weight off! Diets work well at the start, but as we lose weight, our metabolism slows. Compensatory mechanisms start almost immediately and persist almost indefinitely. We must then reduce our caloric intake further and further simply to maintain the weight loss. If we don’t, our weight plateaus and then starts to creep back up—just as every dieter already knows. (It’s also hard to gain weight, but we don’t usually concern ourselves with that problem, unless we are sumo wrestlers.) Virtually every dietary study of the last century has documented this finding. Now we know why.
Consider our thermostat analogy. Normal room temperature is 70°F (21°C). If the house thermostat were set instead to 32°F (0°C), we’d find it too cold. Using the First Law of Thermodynamics, we decide that the temperature of the house depends upon Heat In versus Heat Out. As fundamental law of physics, it is inviolable. Since we need more Heat In, we buy a portable heater and plug it in. But Heat In is only the proximate cause of the high temperature. The temperature at first goes up in response to the heater. But then, the thermostat, sensing the higher temperature, turns on the air conditioner. The air conditioner and the heater constantly fight against each other until the heater finally breaks. The temperature returns to 32°F.
The mistake here is to focus on the proximate and not the ultimate cause. The ultimate cause of the cold was the low setting of the thermostat. Our failure was that we did not recognize that the house contained a homeostatic mechanism (the thermostat) to return the temperature to 32°F. The smarter solution would have been for us to identify the thermostat’s control and simply set it to a more comfortable 70°F and so avoid the fight between the heater and the air conditioner.
The reason diets are so hard and often unsuccessful is that we are constantly fighting our own body. As we lose weight, our body tries to bring it back up. The smarter solution is to identify the body’s homeostatic mechanism and adjust it downward—and there lies our challenge. Since obesity results from a high body set weight, the treatment for obesity is to lower it. But how do we lower our thermostat? The search for answers would lead to the discovery of leptin.
LEPTIN: THE SEARCH FOR A HORMONAL REGULATOR
DR. ALFRED FROHLICH from the University of Vienna first began to unravel the neuro-hormonal basis of obesity in 1890; he described a young boy with the sudden onset of obesity who was eventually diagnosed with a lesion in the hypothalamus area of the brain. It would be later confirmed that hypothalamic damage resulted in intractable