Seizing appetite by the NAPE

’Tis the season to begin newspaper columns with the phrase “’Tis the season,” and who am I to resist?

Failing to resist that particular temptation is of little moment, of course. Failing to resist another temptation endemic to this time of year is not: the temptation to eat…and eat…and eat.

Why do we eat more food than we need to survive, with consequences that range from the annoying (clothes now too snug for comfort) to the serious (diabetes, heart disease, etc.)?

Because as a species, until the last century or so, we’ve been more likely to be short of food than not, and so we are hardwired to eat whatever is put before us–particularly fatty foods which, over the millennia, have been harder for us to come by.

Will power alone is not always–or even very often–enough to enable us to overcome this genetic programming, which is why even if we succeed in losing weight, we almost always put it back on again.

Which naturally has led researchers to look for ways to short-circuit that genetic programming.

We have learned a few things about appetite over the years. Just in 1999, scientists identified ghrelin, a hormone produced in the gut at the times we have trained ourselves to expect food, that produces that “empty” feeling we associate with hunger.

If ghrelin were the only thing at work, we’d probably eat ourselves to death. Fortunately, other body systems produce the opposite feeling. Nerves in the stomach and upper intestine detect the fact those organs are being distended, and tell the brain we’re getting full. As well, various signaling chemicals are released as food is eaten, among them hormones that not only tell your brain you’re full but also tell your stomach to stop passing food along to the intestine–which really makes you feel full.

Then there’s leptin, which is produced by body fat itself and which muffles appetite signals, so that the fatter you are, supposedly, the less you want to eat. Unfortunately, over time our bodies can grow resistant to that signal.

If that all seems fairly straightforward, it isn’t, because there are dozens of other chemicals involved, too, and their interactions with each other and with the brain are complex, to say the least.

And, in fact, a new messaging chemical has been identified, in research reported last week by a group led by Gerald Shulman at the Howard Hughes Medical Institute. It goes by the name N-acylphosphatidylethanolamine, but you’ll be glad to know it’s been abbreviated to NAPE.

Shulman’s group, in working to understand how insulin resistance develops and leads to diabetes, has developed a sensitive method for identifying and measuring fats in tissue samples. Knowing (as noted earlier) that high-fat foods are very satisfying, they set out to use their new fat-detection method to see if any “fat derivatives” that make their way into the bloodstream after a high-fat meal communicate directly with the brain…and they found NAPE.

Fasting rats had low levels of NAPE in the blood; it shot up 40 to 50 percent when the animals were fed high-fat food, and it didn’t increase in rodents served only protein or carbohydrates.

Not only that, but injecting synthetic NAPE into the rats’ abdominal cavities or blood reduced their appetites: at the highest doses, it kept the rats from eating for up to 12 hours. They even went into “siesta” mode, as if they really had eaten a big meal.

Smaller doses delivered directly to the brain had the same effect, suggesting NAPE does indeed communicate directly with the brain.

Next they outfitted 22 rats with vests that allowed them to move freely around their cages while receiving NAPE intravenously. NAPE-receiving rats ate less and lost 10 percent of their body weight, while otherwise appearing normal and healthy.

Shulman’s team is now monitoring NAPE levels in humans, and plans to test NAPE on non-human primates…which, if it pans out, could lead to clinical trials with NAPE or NAPE-like compounds in humans in the not-too-distant future.

None of which helps you this high-calorie holiday season, alas. For now, your–and my!–only hope is willpower.

Good luck. We’re both going to need it.

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