THE CALORIC-REDUCTION THEORY of obesity was as useful as a half-built bridge. Studies repeatedly proved it did not lead to permanent weight loss. Either the Eat Less, Move More strategy was ineffective, or patients were not following it. Health-care professionals could not abandon the calorie model, so what was left to do? Blame the patient, of course! Doctors and dieticians berated, ridiculed, belittled and reprimanded. They were drawn irresistibly to caloric reduction because it transformed obesity from their failure to understand it into our lack of willpower and/or laziness.
But the truth cannot be suppressed indefinitely. The caloric-reduction model was just wrong. It didn’t work. Excess calories did not cause obesity, so reduced calories could not cure it. Lack of exercise did not cause obesity, so increased exercise could not cure it. The false gods of the caloric religion had been exposed as charlatans.
From those ashes, we can now begin to build a newer, more robust theory of obesity. And with greater understanding of weight gain, we have a new hope: that we can develop more rational, successful treatments.
What causes weight gain? Contending theories abound:
The various theories fight among themselves, as if they are all mutually exclusive and there is only one true cause of obesity. For example, recent trials that compare a low-calorie to a low-carbohydrate diet assume that if one is correct, the other is not. Most obesity research is conducted in this manner.
This approach is wrong, since these theories all contain some element of truth. Let’s look at an analogy. What causes heart attacks? Consider this partial list of contributing factors:
These factors, some modifiable and some not, all contribute to heart-attack risk. Smoking is a risk factor, but that doesn’t mean that diabetes is not. All are correct since they all contribute to some degree. Nonetheless, all are also incorrect, because they are not the sole cause of heart attacks. For example, cardiovascular-disease trials would not compare smoking cessation to blood-pressure reduction since both are important contributing factors.
The other major problem with obesity research is that it fails to take into account that obesity is a time-dependent disease. It develops only over long periods, usually decades. A typical patient will be a little overweight as a child and slowly gain weight, averaging 1 to 2 pounds (0.5 to 1 kilogram) per year. While this amount sounds small, over forty years, the weight gained can add up to 80 pounds (35 kilograms). Given the time it takes for obesity to develop, short-term studies are of limited use.
Let’s take an analogy. Suppose we were to study the development of rust in a pipe. We know that rusting is a time-dependent process that occurs over months of exposure to moisture. There would be no point in looking at studies of only one- or two-days’ duration, as we might very well conclude that water does not cause pipe rust since we did not observe any rust forming during that forty-eight hours.
But this mistake is made in human obesity studies all the time. Obesity develops over decades. Yet hundreds of published studies consider only what happens in less than a year. Thousands more studies last less than a week. Still, they all claim to shed light on human obesity.
There is no clear, focused, unified theory of obesity. There is no framework for understanding weight gain and weight loss. This lack impedes progress in research—and so we come to our challenge: to build the hormonal obesity theory.
Obesity is a hormonal dysregulation of fat mass. The body maintains a body set weight, much like a thermostat in a house. When the body set weight is set too high, obesity results. If our current weight is below our body set weight, our body, by stimulating hunger and/or decreasing metabolism, will try to gain weight to reach that body set weight. Thus, excessive eating and slowed metabolism are the result rather than the cause of obesity.
But what caused our body set weight to be so high in the first place? This is, in essence, the same question as “What causes obesity?” To find the answer, we need to know how the body set weight is regulated. How do we raise or lower our “fat thermostat”?
THE HORMONAL THEORY OF OBESITY
OBESITY IS NOT caused by an excess of calories, but instead by a body set weight that is too high because of a hormonal imbalance in the body.
Hormones are chemical messengers that regulate many body systems and processes such as appetite, fat storage and blood sugar levels. But which hormones are responsible for obesity?
Leptin, a key regulator of body fat, did not turn out to be the main hormone involved in setting the body weight. Ghrelin (the hormone that regulates hunger) and hormones such as peptide YY and cholecystokinin that regulate satiety (feeling full or satisfied), all play a role in making you start and stop eating, but they do not appear to affect the body set weight. How do we know? A hormone suspected of causing weight gain must pass the causality test. If we inject this hormone into people, they must gain weight. These hunger and satiety hormones do not pass the causality test, but there are two hormones that do: insulin and cortisol.
In chapter 3, we saw the caloric-reduction view of obesity relies on five assumptions that have been proved to be wrong. This hormonal theory of obesity avoids making these false assumptions. Consider the following:
Assumption 1: Calories In and Calories Out are independent of each other.
THE HORMONAL THEORY explains why Calories In and Calories Out are tightly synchronized with each other.
Assumption 2: Basal metabolic rate is stable.
THE HORMONAL THEORY explains how hormonal signals adjust basal metabolic rate to either gain or lose weight.
Assumption 3: We exert conscious control over Calories In.
THE HORMONAL THEORY explains that hunger and satiety hormones play a key role in determining whether we eat.
Assumption 4: Fat stores are essentially unregulated.
THE HORMONAL THEORY explains that fat stores, like all body systems, are tightly regulated and respond to changes in food intake and activity levels.
Assumption 5: A calorie is a calorie.
THE HORMONAL THEORY explains why different calories cause different metabolic responses. Sometimes calories are used to heat the body. At other times, they will be deposited as fat.
THE MECHANICS OF DIGESTION
BEFORE DISCUSSING INSULIN, we must understand hormones in general. Hormones are molecules that deliver messages to a target cell. For example, thyroid hormone delivers a message to cells in the thyroid gland to increase its activity. Insulin delivers the message to most human cells to take glucose out of the blood to use for energy.
To deliver this message, hormones must attach to the target cell by binding to receptors on the cell surface, much like a lock and key. Insulin acts on the insulin receptor to bring glucose into the cell. Insulin is the key and fits snugly into the lock (the receptor). The door opens and glucose enters. All hormones work in roughly the same fashion.
When we eat, foods are broken down in the stomach and small intestine. Proteins are broken into amino acids. Fats are broken into fatty acids. Carbohydrates, which are chains of sugars, are broken into smaller sugars. Dietary fiber is not broken down; it moves through us without being absorbed. All cells in the body can use blood sugar (glucose). Certain foods, particularly refined carbohydrates, raise blood sugar more than other foods. The rise in blood sugar stimulates insulin release.
Protein raises insulin levels as well, although its effect on blood sugars is minimal. Dietary fats, on the other hand, tend to raise both blood sugars and insulin levels minimally. Insulin is then broken down and rapidly cleared from the blood with a half-life of only two to three minutes.
Insulin is a key regulator of energy metabolism, and it is one of the fundamental hormones that promote fat accumulation and storage. Insulin facilitates the uptake of glucose into cells for energy. Without sufficient insulin, glucose builds up in the bloodstream. Type 1 diabetes results from the autoimmune destruction of the insulin-producing cells in the pancreas, which results in extremely low levels of insulin. The discovery of insulin (for which Frederick Banting and J.J.R. Macleod were awarded the 1923 Nobel Prize in Medicine), changed this formerly fatal disease into a chronic one.
At mealtimes, ingested carbohydrate leads to more glucose being available than needed. Insulin helps move this flood of glucose out of the bloodstream into storage for later use. We store this glucose by turning it into glycogen in the liver—a process is called glycogenesis. (Genesis means “the creation of,” so this term means the creation of glycogen.) Glucose molecules are strung together in long chains to form glycogen. Insulin is the main stimulus of glycogenesis. We can convert glucose to glycogen and back again quite easily.
But the liver has only limited storage space for glycogen. Once full, excess carbohydrates will be turned into fat—a process called de novo lipogenesis. (De novo means “from new.” Lipogenesis means “making new fat.” De novo lipogenesis means “to make new fat.”)
Several hours after a meal, blood sugars and insulin levels start to drop. Less glucose is available for use by the muscles, the brain and other organs. The liver starts to break down glycogen into glucose to release it into general circulation for energy—the glycogen-storage process in reverse. This happens most nights, assuming you don’t eat at night.
Glycogen is easily available, but in limited supply. During a short-term fast (“fast” meaning that you do not eat), your body has enough glycogen available to function. During a prolonged fast, your body can make new glucose from its fat stores—a process called gluconeogenesis (the “making of new sugar”). Fat is burned to release energy, which is then sent out to the body—the fat-storage process in reverse.
Insulin is a storage hormone. Ample intake of food leads to insulin release. Insulin then turns on storage of sugar and fat. When there is no intake of food, insulin levels fall, and burning of sugar and fat is turned on.
This process happens every day. Normally, this well-designed, balanced system keeps itself in check. We eat, insulin goes up, and we store energy as glycogen and fat. We fast, insulin goes