Chapter 5

The Fat Thermostat

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.

Set point is a theory to explain why long term weight loss appears terribly difficult for many people, even those who manage to lose in the short term. The way I usually attempt to explain the idea of set point is through an analogy: Imagine a house in the winter when it is very cold outside. The owner has set the thermostat that controls his natural gas heating system to 80 degrees Fahrenheit. This requires a lot of gas flow and it's too hot to be comfortable, so after a time, the homeowner decides to lower the temperature to 70 degrees. He can do this two ways.

The smart way to lower the temperature is to turn the thermostat down to 70 and wait. Because of heat loss through the walls, the temperature falls in a half hour to 69 degrees. This causes the heater to kick back on, but only until the the temperature rises to 71 degrees. Then it turns off again---or better yet, the heater can stay on all the time, but turn down it's flame and gas flow to precisely the levels needed to maintain 70 degrees. THAT is the smart way to lower the temperature.

The dumb way to lower the temperature is to leave the thermostat set for 80, leave the gas flow and the fire on high, but start opening doors and windows to the outside winter air. This will indeed cool the house, and if one leaves just the right number of windows open, the temperature will stay at 70 even though the thermostat "thinks" it should be 80 and the gas is on high. Obviously this is a stupid way to cool a home in winter because it is wasteful and because it is fighting the thermostat and the heater the whole time. 

Now, if instead of a house, we take a human being and instead of trying to lower temperature, we are trying to lower body weight and instead of gas flow we have calorie intake that is governed by hunger that is in turn largely controlled by a hidden thermostat, perhaps the idea of set point becomes more clear. As long as we don't lower the "thermostat", we can lose weight, but it really is a lot like opening all the doors. The thermostat begins to make us very hungry, trying to increase calorie intake, although with enough strength of will, we can overcome that hunger....for a while just as we can sit in the house with all the doors open. But this really isn't a great way to cool a house and it certainly is a lousy way to lose weight. I have illustrated the house analogy below.


 

Body weight set point

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 & Body-Weight Set Point

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:

  • Insulin
  • Thyroid Hormone
  • Leptin
  • Ghrelin
  • Peptide YY
  • Glucagon-Like-Peptide-1
  • Cholecystokinin
  • Cortisol
  • Amylin
  • Melanocyte Stimulating Hormone

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:

  • Norepinephrine
  • Dopamine
  • Serotonin
  • Neuropeptide Y
  • Agouti-Related Protein (AgRP)
  • Melanocortins (Particularly Melanocortin 4)
  • Cilliary Neurotrophic Factor
  • Anandamide

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:

  • There is no key (the hormone is absent) or the key is broken (the defective hormone can't activate the normal receptor or can only do so weakly)
  • There is no lock (the receptor is missing) or the lock is broken (the normal hormone cannot activate the defective receptor or can only do so weakly)

Specific Hormonal Problems that Influence Body Weight

 

Leptin Resistance:

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 Resistance

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 Excess

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.

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