Why We Get Fat: And What to Do About It (17 page)

One hormone dominates this action, though, and that’s insulin. Astwood pointed this out almost fifty years ago, and it’s never been controversial. As I said, you secrete insulin primarily in response to the carbohydrates in your diet, and you do so primarily to keep blood sugar under control.
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But the insulin also works simultaneously to orchestrate the storage and use of fat and protein. It makes sure, for instance, that your muscle cells get enough protein to do whatever rebuilding and repair is necessary, and it makes sure that you store enough fuel (glycogen and fat and protein as well) to function effectively between meals. And because one place we store fuels for later use is our fat tissue, insulin is the “principal regulator of fat metabolism,” which is how it was described in 1965 by Salomon Berson and Rosalyn Yalow, the two scientists who invented the technology necessary to measure hormone levels in our blood and did much of the relevant research. (Yalow later won the Nobel Prize for this work. Berson certainly would have shared it had he not died before the prize was awarded.)

Insulin accomplishes this job primarily through two enzymes. The first is LPL, lipoprotein lipase, the enzyme I discussed earlier, when we were talking about how rats get obese if their ovaries are removed. LPL is the enzyme that sticks out from the membranes
of different cells and then pulls fat out of the bloodstream and into the cells. If the LPL is on the surface of a muscle cell, then it directs the fat into the muscle to be used for fuel. If it’s on a fat cell, then it makes that fat cell fatter. (The LPL breaks down triglycerides in the bloodstream into their component fatty acids, and then the fatty acids flow into the cell.) As I said previously, the female sex hormone estrogen stifles the activity of LPL on fat cells and so works to decrease fat accumulation.

LPL is the simple answer to many of the questions I raised earlier about the wheres and whens of fattening. Why do men and women fatten differently? Because the distribution of LPL is different, as is the influence of sex hormones on LPL.

In men, LPL activity is higher in the fat tissue of the gut, so this is where men tend to get fat, whereas it’s low in the fat tissue below the waist. One reason men get fatter above the waist as they age is that they secrete less testosterone, a male sex hormone, and testosterone suppresses LPL activity on the abdominal fat cells. Less testosterone means more LPL activity on the fat cells of the gut, and so more fat.

In women, the activity of LPL is high on the fat cells below the waist, which is why they tend to fatten around the hips and butt, and low on the fat cells of the gut. After menopause, the LPL activity in women’s abdominal fat catches up to that of men, and so they tend to put on excess fat there, too. When women get pregnant, LPL activity increases on their butts and hips; this is where they store the calories they’ll need later to nurse their babies. Putting fat on below the waist and behind them also balances the weight of the child growing in their womb in front. After women give birth, the LPL activity below their waist decreases. They lose the excess fat they gained, at least most of it, but LPL activity increases in the mammary glands of their breasts, so they can use this fat to produce milk for the baby.

LPL also happens to be one very good answer to the question of why we don’t lose fat when we exercise. While we’re working out, LPL activity decreases on our fat cells and increases on muscle cells. This prompts the release of fat from our fat tissue, so we
can burn it in our muscle cells, which need the fuel. We get a little leaner. So far, so good. But when we’re done exercising, the situation reverses. Now LPL activity on the muscle cells shuts down, LPL activity on the fat cells shoots up, and the fat cells restock whatever fat they lost during the workout. We get fatter again. (This also explains why exercise makes us hungry. Not only do our muscles crave protein after a workout to restock and rebuild, but our fat is actively restocking, too. The rest of the body tries to compensate for this energy drain, and our appetite increases.)

Since insulin is the primary regulator of fat metabolism, it’s not surprising that it’s the primary regulator of LPL activity. Insulin activates LPL on fat cells, particularly the fat cells of the abdomen; it “upregulates” LPL, as researchers say. The more insulin we secrete, the more active the LPL on the fat cells, and the more fat is diverted from the bloodstream into the fat cells to be stored. Insulin also happens to suppress LPL activity on the muscle cells, assuring that they won’t have many fatty acids to burn. (Insulin also tells muscle cells and others in the body
not
to burn fatty acids but to continue burning up blood sugar instead.) This means that when fatty acids do escape from a fat cell, if insulin levels happen to be high, these fatty acids won’t be taken up by the muscle cells and used for fuel. They’ll end up back in the fat tissue.
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Insulin also influences an enzyme that we haven’t discussed, hormone-sensitive lipase, or HSL for short. And this may be even more critical to how insulin regulates the amount of fat we store. Just as LPL works to make fat cells (and us) fatter, HSL works to make fat cells (and us) leaner. It does so by working inside the fat cells to break down triglycerides into their component fatty acids, so that those fatty acids can then escape into the circulation. The more active this HSL, the more fat we liberate and can burn for fuel and the less, obviously, we store. Insulin also suppresses this
enzyme HSL, and so it prevents triglycerides from being broken down inside the fat cells and keeps the outward flow of fatty acids from the fat cells to a minimum. And it takes just a little bit of insulin to accomplish this feat of shutting down HSL and trapping fat in our fat cells. When insulin levels are elevated, even a little, fat accumulates in the fat cells.

Insulin also turns on a mechanism in the fat cells to pump in glucose—just as it does in muscle cells—and this increases the amount of glucose the fat cells metabolize. This in turn increases the amount of glycerol molecules (a by-product of glucose metabolism) floating around in the fat cells, and these glycerol molecules can now be bundled together with fatty acids into triglycerides, and so more fat can be stored. To assure we have room to store all that fat, insulin also works to create new fat cells in case the ones we already have are getting full. And insulin signals liver cells not to burn fatty acids but to repackage them into triglycerides and ship them back to the fat tissue. It even triggers the conversion of carbohydrates directly into fatty acids in the liver and in the fat tissue, although how much this actually goes on in humans (as opposed to lab rats) is still a subject of debate.

In short, everything insulin does in this context works to increase the fat we store and decrease the fat we burn. Insulin works to make us fatter.

The photo on
this page
shows a particularly graphic example of this fattening effect of insulin, courtesy of the textbook
Endocrinology: An Integrated Approach
by Stephen Nussly and Saffron Whitehead, which the National Library of Medicine makes available online (
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=endocrin
). The caption of this photo is “The effects of insulin on adipose tissue.”

The woman pictured developed type 1 diabetes when she was seventeen. The photo was taken forty-seven years later. In the intervening years, she faithfully injected herself with her daily insulin in the same two sites on her thighs. The result: cantaloupe-sized masses of fat on each thigh. And these obviously have nothing to do with how much she ate, only the fattening or “lipogenic” effect of the insulin. Keep in mind that it took this woman decades to amass these unsightly fat deposits. For her, it would have seemed barely noticeable year to year, just as it does for many of us when we get fat.

(photo credit 11.3)

When we raise insulin levels throughout our body, this is what happens. This is why diabetics often get fatter when they take insulin therapy. (It results from “the direct lipogenic effect of insulin on adipose tissue, independent of food intake,” as explained by the seminal textbook in the field,
Joslin’s Diabetes Mellitus
.) In one study published in
The New England Journal of Medicine
in 2008, type 2 diabetics on intensive insulin therapy gained an average of eight pounds, and almost one in every three of these diabetics gained more than twenty pounds in three and a half years.

Because the insulin level in the bloodstream is determined primarily by the carbohydrates that are consumed—their quantity and quality, as I’ll discuss—
it’s those carbohydrates that ultimately determine how much fat we accumulate
. Here’s the chain of events:

If you’re wondering whether any other hormones make us fat, the answer is effectively no, with one significant exception.
^†

One way to think about what hormones do is that they instruct the body to do something—grow and develop (growth hormones), reproduce (sex hormones), flee or fight (adrenaline). They also make the fuel available for those various actions. Among other things, they signal our fat tissue to mobilize fatty acids and make them available for fuel.

For example, we secrete adrenaline in response to perceived threats. It readies us to flee or fight should the need arise. But if you had to flee a charging lion, say, and you didn’t have the fuel immediately available to run either faster or farther (and maybe both) than the lion, the lion would catch you. So, on seeing the
lion, you secrete adrenaline, and the adrenaline, among other things, signals your fat tissue to dump fatty acids into the circulation. These fatty acids, ideally, will then provide all the fuel you need to make your escape. In this sense, every hormone but insulin works to release fat from our fat tissue. They make us leaner, at least temporarily.

These other hormones, though, have a far more difficult time getting fat out of fat tissue if the insulin level in the circulation is elevated. Insulin trumps the effect of other hormones. It’s all very rational. If there’s a lot of insulin around, it
should
mean there are also a lot of carbohydrates around to burn—that the blood sugar level is high—and so we don’t need or want fatty acids getting in the way. As a result, these other hormones will liberate fat from the fat tissue only when insulin levels are low. (The other hormones work by stimulating HSL to break down triglycerides, but the HSL is so sensitive to insulin that the other hormones can’t overcome its action.)

The one meaningful exception is cortisol. This is the hormone we secrete in response to stress or anxiety. Cortisol actually works to put fat into our fat tissue
and
to get it out. It puts fat in by stimulating the enzyme LPL, just as insulin does, and by causing or exacerbating a condition known as “insulin resistance,” which I’ll discuss in the next chapter. When you’re insulin-resistant, you secrete more insulin and you store more fat.

So cortisol makes us store fat both directly (through LPL) and indirectly (through insulin). But then it works to release fat from our fat cells, primarily by stimulating HSL, just like other hormones. So cortisol can make us fatter still when insulin is elevated, but it can also make us leaner, just like every other hormone, when insulin levels are low. And this may explain why some people get fatter when they get stressed, anxious, or depressed and eat more, and some people do the opposite.

The bottom line is something that’s been known (and mostly ignored) for over forty years. The one thing we absolutely have to do if we want to get leaner—if we want to get fat out of our fat tissue and burn it—is to lower our insulin levels and to secrete
less insulin to begin with. Here’s how Yalow and Berson phrased it back in 1965: releasing fat from our fat tissue and then burning it for energy, they wrote, “requires only the negative stimulus of insulin deficiency.” If we can get our insulin levels to drop sufficiently low (the negative stimulus of insulin deficiency), we can burn our fat. If we can’t, we won’t. When we secrete insulin, or if the level of insulin in our blood is abnormally elevated, we’ll accumulate fat in the fat tissue. That’s what the science tells us.