In 1983, William Bennett and Joel Gurin, both physicians, published a book titled "The Dieter's Dilemma: Eating Less and Weighing More" in which they argue that human body weight is "set" or pre-determined by an internal "fat thermostat". The theory holds that when body weight drops below the set point, the "fat thermostat" causes a drop in caloric output and an increase in appetite until body weight has climbed to the set point again, at which time caloric intake and output normalize. They postulate a mechanism involving neurochemistry and hormones.
Figure 5: There is a smart and a dumb way to cool a house in winter. The smart way is to turn down the thermostat. The dumb way is to NOT turn down the thermostat but instead open doors and windows to the outside until the temperature reaches 70 degrees.
Figure 6: Likewise there is a smart and a dumb way to lose weight. The smart way is to turn down the "weight thermostat". The dumb way is to drastically lower calorie intake and try to starve oneself into thinness.
But of course, the body doesn't really "think" and there is not a thermostat. These are just useful analogies. So in the next chapters we'll explore the REAL mechanisms in the human body that cause obesity. We'll start with hunger.
Chapter 6: What Controls the "Fat Thermostat": Hormones and Neurotransmitters
In the last two chapters I have tried to show that people don't become obese because they deliberately overeat but instead because their body "thinks" that it needs to be heavy; because the set-point is too high. To refer back to the last chapter, this means that either the fire (appetite) is too high or the "window" (metabolism) needs to be opened (increased) or both. In this chapter we will focus on appetite.
Now let's look at what science is teaching us about how the body regulates the set-point .
It's done with hormones and brain chemicals that control hunger and metabolism.
Hormones are chemicals made in one part or tissue of the body that influence the functioning of a different part or tissue. Hormones are generally produced in very small amounts and are extremely potent so that tiny amounts cause big effects.
A number of hormones are known to affect body weight and they exert these effects by turning appetite and/or metabolism up or down. In some sense, these hormones ARE "the" fat thermostat. They are, at least in part, the regulators of body-weight set point and when their effects are enhanced or diminished, body weight can be profoundly affected.
Hormones exert their effects upon tissue by "binding" to "receptors" found on the outside (the bloodstream side) of cells. These receptors are proteins that fold-up in very precise ways so that they have a cleft or hole in them that is as intricate and complex as the lock in a door. And just like the lock in a door, hormone receptors can only be "opened" by the right key; the key made to fit that specific lock. The hormone is the key.
So when an individual hormone molecule that affects say muscle tissue is secreted into the bloodstream from say the pancreas, it gets pumped by the heart and dispersed by diffusion until, at some point, it bounces into the "lock" of its receptor on a muscle cell. You might imagine that this is a very unlikely "bounce", and indeed it is, but molecules like hormones are so incredibly tiny that they bounce around trillions of time per second so that even a very rare collision happens pretty quickly. And once the hormone "key" settles into its receptor "lock", it becomes stuck and won't bounce out again.
Once the hormone key has found its lock, the "door" opens. To dispense with the analogies, once the hormone binds to its cell-surface receptor, the receptor undergoes a conformational (shape) change that affects the inside of the cell, often triggering what is known as a "cascade": the re-shaped receptor protein triggers a chemical reaction inside the cell and that reaction triggers many more reactions, each of which, in turn, trigger many others until trillions upon trillions of reactions have occurred. A single hormone molecule, just one, affects trillions of molecules inside a living cell.
Hormones are like a key that unlocks the floodgates of a dam. The key itself is tiny but the effects that it can produce are mighty
It turns out that some hormones play a huge role in regulating body weight because they affect appetite and metabolism. For the moment, let's focus only upon the appetite-affecting hormones.
There are a number of them:
I'll talk about some of these appetite affecting hormones later, but for now just know that they exist and that there are probably many more that have not yet been discovered.
Brain Chemicals and Appetite:
Chemicals that are made in the brain and that affect other parts of the brain are generally called "neurotransmitters". The are essentially no different than hormones expect that they often only travel very tiny distances to find their receptors.
Because neurotransmitters directly affect the brain, they tend to have dramatic effects upon behavior, and the behavior we are interested in here is, of course, eating. There are several neurotransmitters that affect appetite:
Again, we'll discuss some of these again later but for now, just understand that they exist
These then are some of the known hormones and neurotransmitters that influence appetite. To put it another way, these are some of the control signals that regulate the fat-thermostat or the body-weight set-point.
This means that if the thermostat is set too-high, if the body "believes" that it needs to be fat, the problem might have something to do with these hormones and neurotransmitters.
And it does.
Remember that hormones and neurotransmitters are like keys and that their receptors are like locks and that the "key" must be inserted into the "lock" in order for things to work properly. Things stop working when the lock and key no longer fit together. There are a number of reasons why this can happen:
Specific Hormonal Problems that Influence Body Weight
Leptin is an appetite suppressing hormone made by fat cells. It works by affecting the hypothalamus of the brain where is binds to receptors and inhibits the effects of two appetite stimulating hormones, neuropeptide Y and anandamide. It also stimulates the production of the appetite-suppressing hormone called melanocyte stimulating hormone.
Leptin was discovered in 1994 and found to be absent or lacking in a strain of obese mice called "Ob". At first, leptin was hailed as a potential cure for obesity because, when it was injected into these obese mice, they lost dramatic amounts of weight. To refer back to our earlier "lock and key" analogy, "Ob" mice had no keys and normal locks and once the keys were provided, the locks "opened" and the mice became thin.
To make a complicated tale simple, it didn't work that way in humans. Overweight humans seem to have lots of normal leptin (keys) but defective leptin receptor proteins. To put it another way, many overweight humans are leptin resistant; the keys are normal but the locks are screwy. Thus, no matter how much leptin people have in their blood, it can't trigger the receptor and thereby lower appetite and set-point.
Now the REALLY interesting question is why and how people become leptin resistant. It doesn't seem to be genetic. Rather, it appears that leptin resistance is acquired; that it is caused by something in the environment. As I will show you in the next chapter, we may already know what that "something" is and it's in nearly everything we eat.
Insulin is well known as the "diabetes" hormone. Its discovery and introduction in American medicine in the early 1920s was an absolute miracle for people suffering type-1 (childhood-onset) diabetes. Patients with type-1 diabetes cannot make insulin because the cells in the pancreas that normally produce it become killed-off (perhaps by a virus). So type-1 diabetes is caused by a lack of insulin (no "key")
Type-2 diabetes is the converse of type-1. In type-2 diabetes, people have normal insulin levels but they become resistant to that hormone. The receptor (lock) becomes less able to respond to insulin.
But insulin also suppresses appetite by interacting with receptors in the hypothalamus region of the brain. This means that when people develop insulin resistance, not only does their blood sugar level begin to increase; so does their appetite. And with appetite, increases weight which leads to more severe insulin resistance and so on.
Insulin resistance and visceral fat (fat that is not under the skin but inside the abdomen surrounding the organs) are strongly linked to one another and to hypertension and cardiovascular risk. This is more generally known as the Metabolic Syndrome and will be discussed later in greater detail
Insulin resistance isn't only caused by weight gain, as we'll see soon, there are a number of causes including a number of substances in food.
Ghrelin is an appetite-increasing hormone (it makes you hungry). Levels of Ghrelin normally fall after a meal and they do so because of stretching of Ghrelin-producing cells within the stomach lining. Any time the stomach is distended, Ghrelin levels are "supposed" to fall. This is felt to be the principle mechanism accounting for the drop in hunger experienced by patients who have undergone stomach-shrinking bariatric surgery and it is likely the reason why drinking abundant water may help suppress appetite.
The hormonal regulation of body weight is extremely complex and the purpose of this brief chapter is merely to make the reader aware of how hormones work generally and how certain hormones work to affect weight specifically.
I still have not addressed the central question that I posed at the beginning of this book: namely what ULTIMATELY causes obesity. I have outlined how the proximal causes are simple and result from long-term energy imbalance. I have tried to show that such energy imbalance results from abnormal hunger and metabolism but not from some sort of willful failure to control food intake. I attempted to demonstrate that body weight is no "accident" but is in a very real sense "controlled" in much the same way that the temperature of a home is control by a thermostat setting. Finally I have established the notion that the body's "fat thermostat" is controlled mostly by hormones. When those hormones function normally, a healthy body weight is "dialed-in" so that significant unhealthy weight gain is unlikely to occur. Conversely, when those hormones or the systems the interact with FAIL to perform normally, THEN body weight can change in a direction that is not healthy, most commonly, towards obesity. The only remaining question is why?
What causes weight-regulating hormones to malfunction and cause obesity?
What is making America fat?The answers to this question are the subject of the next chapter.