Notes from: The Hungry Brain by Stephan Guyenet
The brain is in charge of appetite, eating behavior, physical activity, and body fatness, and therefore the only way to truly understand overeating and obesity is to understand the brain.

In a study published in 1988, Sclafani's team should that when they infused partially digested starch directly into the rat's stomachs while they drink cherry-flavored water, the rats developed a preference for that flavor over the grape flavor. And the opposite preference developed when they repeated it with the grape flavor. Even though the starch never entered their mouths, after 4 days, the rats displayed a near-total preference for the starch-paired flavor.

The most highly palatable foods tend to be dense in easily digested calories and combine multiple innately preferred food properties in highly concentrated form ... These are the foods that are most likely to cause cravings and a loss of control over eating, because their physical properties make them exceptionally reinforcing, motivating, and palatable. Researchers have an umbrella term for this combination of effects on the brain: food reward. Highly rewarding foods are those that seduce us.

Habituation is one of the key tricks we use to distinguish important events from unimportant noise... the more we're exposed to a stimulus within a short period of time, the less we respond to it... we tend to eat more total food when we're presented with a large variety of foods. This goes a long way toward explaining what researchers call the buffet effect. We tend to overeat spectacularly at buffets ... we don't have the opportunity to habituate to any particular food, because every few bites, we're eating something new.

There are huge individual differences in that some people will work really, really hard to get access to food, and other people will only work a little bit ... People who are overweight or obese find food more motivating than lean people do, and this leads them to eat more. However, these studies don't tell us whether a high relative reinforcing value of food (RRV-food) causes people to gain weight, or whether something about the overweight state causes RRV-food to increase.

The diets of non-industrial cultures vary widely, yet they share important commonalities that fundamentally differentiate them from the diets of people living in modern affluent nations... Here are three prominent characteristics these diets have in common:
First, they included limited variety of foods...
Second, they have a limited ability to concentrate the reinforcing properties of food. With only the most basic processing methods at their disposal, non-industrial cultures are forced by necessity to eat food in a less calorie-dense, less refined, less rewarding state...
Third, they use few cooking methods.

Allow me to end the [fat vs sugar] debate by stating what most researchers find quite obvious: it's both. In particular, the combination of concentrated sugar and fat in the same food is a deadly one for our food reward system. it's also a pairing that rarely occurs in nature...

Modern food chemists have created or isolated a vast number of seductive flavors that compel us to buy food.

"Life is a game of turning energy into kids," says Herman Pontzer, an associate professor of anthropology at the City University of New York...

The idea of moderation in eating is totally foreign to hunter-gatherers. In fact, Wood, Hill, and Pontzer explained that hunter-gatherer eating habits can be downright gluttonous... men eating 5 lb of fatty meat each in a sitting, drinking one and a half liters of pure honey, or eating 30 wild oranges similar to the fruit we buy in the grocery store... "They fully embrace the idea of 'eat as much pure fat as you can possibly eat' "... Yet despite the fact that they guzzle sugar and fat when available, neither the Hadza nor the Aché have obesity... How can they engage in such gluttonous behavior and yet remain lean? The energy balance equation we encountered in chapter 1 allows only one possible answer: their long-term average energy intake must match their energy expenditure. The reality of hunter-gatherer life is that true starvation is rare, yet they often don't get as many calories as they would like.

Don't make it too easy for yourself to eat food throughout the day. Even effort barriers as small as having to open a cabinet, twist off a lid, peel and orange, or shell nuts can make the difference between eating the right amount and overeating. Keeping easy, tempting foods in plain sight, such as an open bag of chips or bowl of candy, creates a situation that is simply too tempting for the parts of our brains that are constantly on the lookout for a good deal.

Is there anything we can do to fight our natural tendency to short-change our future selves? Research from Leonard Epstein's group and others suggests that the answer is yes - by giving the rational brain a little boost using an exercise called "episodic future thinking." This phrase is a complex-sounding term for a technique that's actually quite simple: Before making a decision, you imagine yourself in the future. When making a decision about something that pits your present self versus your future self, such as whether or not to eat a pastry, first imagine positive events in the future, such as your birthday or an upcoming vacation. Place yourself in the scene and imagine yourself enjoying it. The more vivid the imagery the better. This process fires up the regions in your prefrontal cortex that process abstract concepts like the future and therefore causes your brain to intuitively weight the future more heavily in its decision-making process. This attenuates delay discounting. Epstein's research shows that episodic future thinking reduces the intake of tempting, calorie-dense foods by nearly one-third in overweight women, and the same truth works for overweight children as well.

The body's thermostat rides in the hypothalamus. It receives temperature information from sensors in the body and coordinates the physiological and behavioral responses necessary to maintain ideal body temperature. Similarly, the hypothalamus (and other brain regions, to a lesser extent) is the body's lipostat - the brain region that regulates appetite and body fatness. It receives information about the size of fat stores from signals, including leptin, and coordinates the physiological and behavioral responses necessary to maintain adiposity. As Leibel and Hirsch observed in their weight loss studies, if a person loses fat, the lipostat engages a coordinated suite of responses that work to increase energy intake, reduce energy expenditure, and thereby regain the lost fat... The lipostat isn't broken in garden-variety obesity - it simply regulates adiposity at a higher set point, analogous to turning up the thermostat in your home.

...it seemed as if the diets were not just passively causing weight gain but actually changing the set point of the lipostat.

... First, calorie-dense, highly rewarding food may favor overeating and weight gain not just because we passively overeat it but also because it turns up the set point of the lipostat ... Second, focusing the diet on less rewarding foods may make it easier to lose weight and maintain weight loss because the lipostat doesn't fight it as vigorously. this may be part of the explanation for why all weight-loss diets seem to work to some extent - even those that are based on diametrically opposed principles, such as low-fat, low-carbohydrate, paleo, and vegan diets. Because each diet excludes major reward factors, they may all lower the adiposity set point somewhat.

...a substantial amount of indirect evidence suggests that a high intake of protein may be able to lower the adipocity set point...

... findings demonstrate that restricting carbohydrate without increasing protein doesn't cause the same weight-loss effect as a typical higher-protein, low-carbohydrate diet, suggesting the carbohydrate restriction per se isn't actually the key ingredient in low-carbohydrate diets. rather, advice to eat a low-carbohydrate diet may be effective simply because it's an easy way to get people to eat high-protein foods and reduce major food reward culprits.

So what's holding us back from curing human obesity? In a word, ethics. While we already have the technical ability to genetically engineer humans, and probably directly manipulate the brain circuits that control eating, we don't currently consider it ethical. And there are many good reasons for this, one of which is that we haven't yet demonstrated the safety of this technology.

...the more signs of damage we found in a person's hypothalamus, the more likely he was to have obesity. "The scariest implication is that the food we eat may cause damage in areas of the brain that we need to regulate our body weight and our appetite, as well as our blood sugar and to some degree, our reproductive health." Just as a tumor in Eliza Moser's hypothalamus caused her to develop obesity, a milder form of brain damage could be contributing to our own expanding waistlines.

Let's recap what I've proposed thus far. We overeat because we're surrounded by seductive, calorie-dense food that's a great deal. The food's high reward value increases the set point of the lipostat, though not necessarily permanently, and this further facilitates overeating. At the same time, overeating itself spikes leptin levels and injures the hypothalamus by a mechanism we have yet to nail down (likely involving diet quality in addition to quantity). These two simultaneous hits cause the hypothalamus to lose sensitivity to the leptin hormone, meaning that it requires more leptin, and therefore more body fat, to hold off the starvation response that drives us to overeat. This time, the increase in your set point is permanent, or at least difficult to reverse. The lower limit of your comfortable weight creeps up.
     To be clear, this is a working hypothesis that needs to be tested further before we can hang our hats on it. We don't yet have a complete understanding of how obesity develops and is maintained, but each year brings us closer to the answer.

High-satiety foods have some combination of low calorie density, moderate palatability, high protein, and/or high fiber, such as beans, lentils, fresh fruit, vegetables, potatoes and sweet potatoes, fresh meat and seafood, oatmeal, avocados, yogurt, and eggs. The exceptionally high satiety value of potatoes is undoubtedly one of the reasons why the "potato diet" we encountered in chapter 3 is effective. But if you cover your potato with calorie-dense flavorings such as butter and cheese, or deep-fry it into French fries, all bets are off.

... each person overate the same food by the same amount, under controlled conditions, for the duration of the study.
     If overeating affects everyone the same, then they should all have gained the same amount of weight. Yet Bouchard observed that weight gain ranged from 9 to 29 pounds! Identical twins tended to gain the same amount of weight and fat as each other, while unrelated subjects had more divergent responses. 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.

So far, researchers have identified nearly 100 genes that influence adiposity - yet together, these genes explain less than 3% of the differences in adiposity between people. Clearly, there's still work to do... 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 adipocity. This suggests that genetic differences in brain function are the primary reason why some people are fatter than others.

As Francis Collins, geneticist and director of the National Institutes of Health, is fond of saying, "Genetics loads the gun, and environment pulls the trigger." Unless you have a faulty gun, which is rare, if you don't pull the trigger, it doesn't discharge.
     A few lucky people are so genetically resistant to obesity that they're unlikely to develop it under any circumstances. A few others are so genetically susceptible that they may carry excess fat even in a very healthy environment. For the rest of us, the environment in which we find ourselves has a major impact on our weight.

...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 a simple as that."

In 1916, the Viennese neurologist Constantin von Economo begin seeing patients with a previously unknown brain disorder. People afflicted with the disorder would sleep excessively - up to 20 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 20th century, afflicting as many as 1 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.

Chronic restriction of sleep periods to 4 hours or 6 hours per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks.

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.

Sleep loss doesn't just affect the lipostat - it also undermines our ability to control the very impulses it activates.

Cortisol and related compounds cause leptin resistance in the hypothalamus. In 1997, a Swiss research team led by Katerina Zakrzewska determined that removing cortisol from the circulation of rats makes them exquisitely leptin-sensitive, and also lean... Incrementally increasing their cortisol levels makes the rats incrementally less leptin sensitive and incrementally fatter.

At any level of overall adiposity, chronic stress seems to shift the distribution of body fat toward the visceral cavity, where it tends to reach metabolic havoc.

Yet there's another, more common-sense reason why some of us overeat when we're stressed, and research is increasingly suggesting that it could be important: junk food simply makes us feel better emotionally.

As predicted by Dallman's comfort food hypothesis, the group that drank sugar water showed a smaller stress response than the group that drank plain water. It appeared that sugar helped them feel better in the face of stress. Yet it's not just sugar: Dallman and others have since shown that giving rats access to a high-fat food does the same thing.

"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 [for dampening the stress response].

Ulrich-Lai's findings have a valuable practical implication: the brain contains a natural stress relief pathway that we can tap into using a variety of everyday behaviors. "If we understand that [built-in] stress relief pathway," explains Ulrich-Lai, "then we might be able to find other ways to target it, either behaviorally or using drugs." Why would we want to find other ways to target it besides comfort food? Because eating calorie-dense comfort food too often can make us gain weight and degrade our health. If we might gain the same stress busting benefit from any rewarding behavior, then why not choose something more constructive, like calling a friend, jogging, gardening - or romance?

... Here's an intuitive example that relates more closely to our subject of interest. When you lose weight, your brain detects falling levels of leptin and increases your motivation to eat. In that case, your brain is using an internal input to regulate a behavioral output, and it happens largely outside of your conscious awareness. Here's the point I'm driving toward: the outputs of your brain, including your appetite and eating behaviors, are determined by the input cues it receives. Some of these cues are processed by conscious circuits and we're very much aware of how they affect us. Many others are processed by non-conscious circuits, which influence our physiology and behavior in ways that we have little awareness of, and little direct control over. Yet they can nevertheless have a substantial impact on our lives.

Six Steps for a Slimming Lifestyle
1. Fix your food environment. get rid of all tempting, calorie-dense foods that are easy to grab and eat in your home and work environment. Reduce your exposure to food cues in general. Create effort barriers to eating.
2. Manage your appetite. Choose foods that have a lower calorie density, higher protein and or fiber content, and a moderate level of palatability. This tends to include simple foods that are closer to their natural state.
3. Beware of food reward. Keep rewarding foods such as chocolate, pizza, potato chips, tortilla chips, French fries, cookies, cake, and ice cream, out of your personal food environment.
4. Make sleep a priority.
5. Move your body. Regular physical activity can help manage your appetite and weight in at least two ways. First, it increases the number of calories you use. Second, physical activity may also help maintain the lipostat in the brain.
6. Manage stress.