The Hungry Brain: Outsmarting the Instincts That Make Us Overeat

by Stephan Guyenet

Palmiter’s and Lowell’s research is increasingly converging on a small area of the brain stem called the parabrachial nucleus that receives input (direct and indirect) from NPY neurons, POMC neurons, and NTS neurons. The parabrachial nucleus could end up being a master regulator of hunger and satiety that plugs into action selection circuits—but this remains to be seen.

Plain potatoes were off the charts—far more filling than any other food.

This only works up to a point, however; you can only trick the brain so much. A belly full of lettuce isn’t going to cut it.

Sticking with simple foods can help us restrain our calorie intake without feeling hungry.

satiety is a function of caloriedensitiy and palatability and fat content and fiber content and protein content. also volume, since this is what distends the stomach, but to a lesser extent.

The third most influential factor Holt and colleagues identified is a food’s fat content. The more fat it contained, the less filling it was per calorie.

adding fat to food is a highly effective way to increase your calorie intake without increasing your satiety much, and limiting added fat helps reduce calorie intake without sacrificing satiety.

A fourth critical factor that Holt’s team identified is fiber. The more fiber a food contained, the more filling it was.

In clinical trials, the Paleolithic diet has often outperformed conventional diets both for weight loss and metabolic improvements, explaining its popularity.

in modern affluent nations like the United States, genetic differences account for about 70 percent of the difference in body weight between individuals.

Furthermore, not only did twins gain a similar amount of fat, they even gained it in the same places. If one person stored the excess fat inside his abdominal cavity—the most dangerous place to gain fat—his twin usually did the same.

In a carefully controlled overfeeding study, his team showed that the primary reason some people readily burn off excess calories is that they ramp up a form of calorie burning called “non-exercise activity thermogenesis” (NEAT). NEAT is basically a fancy term for fidgeting. When certain people overeat, their brains boost calorie expenditure by making them fidget, change posture frequently, and make other small movements throughout the day. It’s an involuntary process, and Levine’s data show that it can incinerate nearly 700 Calories per day! The

By now, you should have a pretty good guess what organ these genes tend to influence: the brain. Although some genes relate to other processes such as fat metabolism, the lion’s share exert their influence in the brain, and of those, many act via brain circuits that are already known to regulate food intake and adiposity (such as POMC neurons and their downstream targets).

genetic confirmation of the theory that bran and not periphery ccounts for most variance in obesity

A century ago in the United States, people carried the same genes we do today, yet few people had obesity. What has changed isn’t our genes, it’s our environment—our food, our cars, our jobs. This leads us to a critical conclusion about obesity genes: In most cases, they don’t actually make us fat, they simply make us susceptible to a fattening environment. In the absence of a fattening environment, they rarely cause obesity.

Their volunteers ate nearly 300 more Calories per day when they were sleep-deprived than when they were well-rested. “In our experience,” explains St-Onge, “sleep restriction increases food intake. It’s as simple as that.”

The story begins in 1916, when the Viennese neurologist Constantin von Economo began seeing patients with a previously unknown brain disorder. People afflicted with the disorder would sleep excessively—up to twenty hours per day—scarcely leaving time for other activities. Encephalitis lethargica, as von Economo named the disorder, swept through Europe and North America in the early twentieth century, afflicting as many as one million people. Most patients were left either dead or permanently disabled by the brain damage it caused. By 1928, the disease vanished as suddenly as it had appeared, and few cases have been reported since. To this day, we still aren’t sure what caused it, although many believe it was triggered by an infectious agent.

spooky.

The fundamental importance of sleep is highlighted by the fact that all animals with a nervous system sleep, or at least enter sleeplike states. Saper explains that “every species that we’ve looked at, even going back to simple invertebrates like sea slugs, tend to have rest-activity cycles.” He believes animals need sleep because neurons require periods of rest for the biochemical processes that support learning.

Importantly, volunteers felt sleepier for the first few days of sleep restriction, but after that, “subjects were largely unaware of these increasing cognitive deficits.” This suggests that people who short themselves on sleep may not even be aware of how poorly they’re performing.

Essentially, when you don’t sleep enough, your lipostat mistakenly thinks you need more energy, which activates your food reward system and causes you to eat more without intending to and often without even realizing it.

Twenty-nine percent of American adults get six hours of sleep or fewer per night, up from 22 percent in 1985.

“When you have inadequate sleep,” explains Pardi, “you’re probably less likely to live in accordance with your own health goals. You’re less likely to get into bed on time, you’re less likely to go to the gym, and you’re less likely to have your eating behaviors align with your long-term health goals.”

This suggested that the human body must quite literally contain a twenty-four-hour(ish) clock. Research over the ensuing half century has confirmed this, although we now know there is more than one clock. In fact, there are thirty-seven trillion of them: a tiny molecular timepiece in nearly every one of your cells.

The system that evolved over billions of years to synchronize the body’s daily rhythms to the cycle of the sun is easily fooled by modern technology.

Not only can the master clock desynchronize from the day-night cycle of the sun, but individual organ clocks can desynchronize from one another. For example, the SCN master clock can become desynchronized from the clocks in the intestine, the liver, the pancreas, and other organs that regulate digestion and metabolism. That’s because the latter group of clocks can be set by meal timing, and as far as they’re concerned, the meal signal is stronger than the one coming from the SCN.

What would normally be a harmonious performance is reduced to a disorganized cacophony. Researchers call this circadian desynchrony and hypothesize that it leads to metabolic problems and weight gain. To test this idea, Arble studied two groups of mice, both eating the same fattening diet. One group had access to food only during the twelve hours of the day when they would normally be awake and active, while the other only had access to food during the twelve hours of the day when they would normally be asleep.139 Under normal, unrestricted conditions, mice eat about two-thirds of their food during the wake cycle and one-third during the sleep cycle. In Arble’s experiment, however, they could only eat during one period or the other, leading to two circadian conditions: one in which digestive and metabolic clocks were synchronized with the master clock in the brain, and one in which they were desynchronized. Surprisingly, mice in both groups ate the same amount of food. Yet after two weeks, a striking trend began to emerge: the synchronized mice were hardly gaining weight, while the desynchronized mice were gaining fast. By the end of the six-week experiment, the desynchronized mice had gained nearly two and a half times more weight than the synchronized mice, and they tended to have more body fat as well. They were eating the same number of calories but metabolizing them differently.

This suggests that what is really fattening in these experiments is not simply fattening food but the combination of fattening food and circadian desynchrony.

It’s likely that we could stay slimmer and healthier with less effort if we took better care of our circadian clocks.

Your body is preparing to fight off a grizzly bear, even if the actual threat is an Excel spreadsheet.

lol

The amygdala also makes its own CRF,

Several large studies have shown that people with higher stress levels tend to gain more body fat over time than people with lower stress levels—and this fat gain occurs particularly in the abdominal area, resembling a mild form of Cushing’s syndrome

Guyenet ought to make a bigger point of distinguishing visceral and subcutaneous fat.

He frequently used dexamethasone, a cortisol-like drug, to treat specific blood disorders that benefited from suppressing the immune system. “He said the first thing you see when you give dexamethasone,” recalls Mary Dallman, “is that the kids would start eating like crazy—and you knew the treatment was going to work.” This led her to study the effect of cortisol and related compounds on calorie intake in rodents.

What is it about comfort food, exactly, that dampens the stress response? Is it the body’s metabolic response to sugar, fat, and/or calories, or is it the food’s reward value itself? Yvonne Ulrich-Lai, a neuroscience researcher at the University of Cincinnati, set out to answer this question. She and her team offered rats intermittent access to small volumes of sugar water, water sweetened with the calorie-free sweetener saccharin, or plain water, and then measured the activation of their HPA axis following restraint stress. She hypothesized that sugar’s stress-busting effect is due to its metabolic impact on the body, not its rewarding effects in the brain, and therefore that saccharin would be ineffective. “The result,” explains Ulrich-Lai, “was completely opposite my hypothesis. The saccharin worked just as well as sugar.” Subsequent experiments confirmed that the sweet taste itself was responsible.

Subsequent experiments confirmed that the sweet taste itself was responsible.

this might explain my gum habit.

Initially, surgeons assumed the obvious: These procedures work because they reduce stomach volume and digestive efficiency, so the recipient simply can’t fit much food into his stomach and also ends up flushing calories down the toilet instead of absorbing them. But when researchers took a closer look, the story turned out to be much more interesting. People who undergo these procedures still have the digestive capacity to eat enough calories to sustain obesity, and they absorb calories nearly as well as they did before surgery. Yet they simply lose their desire to eat rich foods. While before surgery, they may have craved large portions of hamburgers, fries, and soda, after surgery they gravitate toward smaller portions of lighter fare, such as vegetables and fruit.

hmm i thought the story on gastric bypass procedures was more tentative. thereis also the issue of whether the postoperativepeeps eat better bexause it is a good excuse for genera commitment to healthier eating.

Just in case you think the change in food preferences might be a conscious choice on their part, let me add a critical detail: Researchers see similar effects on appetite and food preferences in obese rats and mice who have undergone the same procedures.

ah. hehas anticipated my objection.

If the nonconscious, impulsive brain is so influential, and if it acts according to the cues it receives, then the obvious path to effective weight management is to give it the right cues. How do we do that? We can divide approaches into two categories: things we can do as a nation and things we can do individually.

this is a perfect disrillation of the thesis and its most salient corrolaries.

obviously we as individuals should be more interested in one of them. it occurs to me that this might nreak down along socialist/libertarian lines.

In reality, the situation is even more challenging, because not everyone overeats. If we average 218 excess Calories, what that really means is that some people don’t overeat at all, while others overeat by 400 Calories or more per day. And the latter population is the one that public health measures would have to target.

Humble arithmetic suggests that halfhearted efforts aren’t going to cut it.

That said, what tools do we have at our disposal? The first strategy is simply to give people information on how to eat a healthy diet. Unfortunately, as we’ve seen, that approach by itself seems to have little impact on calorie intake. People do need good information to make good choices, but information alone isn’t enough to substantially change behavi...

The striatum is often divided into two sections: the dorsal (upper) striatum, and the ventral (lower) striatum, which is also commonly called the nucleus accumbens. These play different roles in selection, a topic to which we’ll return.

Many neuroscientists believe we become aware of decisions after they’ve already been made by unconscious parts of the brain. Redgrave: “You do realize with these ideas there is a really, really horrendous implication. We become aware of what is selected after it’s been selected, not before. You have all these competing things, one wins, and you become aware of that winner.” The “horrendous implication” is that we can’t have free will if our decisions are made unconsciously.

I’m using the phrase conditioned flavor preference because it’s the established scientific term; however, typically, the conditioned “flavor” is an odor. In other words, it’s detected by olfactory receptors in the nose rather than taste receptors on the tongue.

excellent point.

Nucleotides, the building blocks of DNA and RNA, are also recognized as umami by the tongue. This is why mushrooms taste meaty.

this is fascinating, but the second sentence doesnt follow logically from the first. aremushrooms particularly enriched in dna?

Rats can be conditioned to like salt by depriving them of it, but they don’t spontaneously seek it like humans do. Sodium is an essential nutrient, humans lose a lot of it through sweat, and most wild environments don’t supply very much of it. This may explain why salt is the only micronutrient (essential vitamin/mineral) we can taste at the concentrations normally found in food.

There isn’t any refined food in a wild environment, and hunter-gatherers tend to have a fairly diverse diet, so it was probably difficult for them to meet their energy needs without also meeting their need for all other essential nutrients. This is supported by the fact that existing and historical hunter-gatherer groups tend to have very low rates of vitamin and mineral deficiency. There may have been no need to evolve a system to seek vitamins and minerals because deficiencies weren’t a major threat to reproductive success, particularly when compared to the much higher risk of insufficient calories. Salt may be an exception. We’re probably wired to taste and enjoy it, like certain other animals, because it was a limiting nutrient in the wild. In contrast, we haven’t evolved the ability to taste and enjoy vitamins or most minerals.

regarding why we do not seem to have a drive for minerals as we do for salt

The evidence that MSG is directly harmful to health isn’t particularly compelling. People commonly attribute uncomfortable post-meal symptoms to MSG, but double-blind trials have generally failed to support this idea. Much of the hoopla over MSG relates to its ability to cause damage to a brain region called the hypothalamus, and therefore cause obesity, when injected into newborn animals (via a phenomenon called excitotoxicity). However, this appears to be irrelevant to typical levels of MSG in the diet, which don’t elevate blood levels, much less brain levels, of glutamate significantly.

obesity is a leading cause of infertility.