Appeasing the lipostat: moderate flavor diet ,exercise and low-carbohydrate,High-protein diet
APPEASING THE LIPOSTAT
If the brain regulates adiposity, then how does a person go from being lean to overweight or obese? And can this process be reversed? We know that in each instance of homeostasis, such as heart rate, body temperature, and adiposity, the body defends a certain set point value against changes—but that doesn’t mean set points are inflexible. For example, your body temperature set point can increase in response to infections, a phenomenon we call fever. When you have a fever, your brain doesn’t lose control of temperature regulation—it deliberately regulates it around a higher set point to fight the infection. Your body turns up its thermostat. Similarly, the set point of the lipostat can be turned up and, some evidence suggests, turned down.
Leibel’s and Hirsch’s weight-loss studies lend scientific rigor to a common-sense conclusion: Different people defend different adiposity set points. In lean people, the lipostat defends a low-adiposity set point against fat loss, which makes great sense from an evolutionary standpoint—a lean person can’t afford to lose much fat. Yet what makes less sense is that among people with obesity, the lipostat defends a high-adiposity set point. Somehow, the hypothalamus has “decided” to defend an obese body type rather than a lean one, even though a person with obesity carries much more fat than is necessary to avoid starvation and infertility. In fact, it makes even less sense than that, because excess adiposity is one of the leading causes of infertility and premature death in the affluent world.54
Many researchers, including myself, speculate that the lipostat behaves abnormally because it’s been placed in an unfamiliar situation: The hypothalamus is wired to keep us healthy and fertile in an environment that disappeared long ago. In today’s environment of plentiful, tasty, refined, calorie-dense food, low physical activity requirements, and other unnatural characteristics, the lipostat essentially misfires, driving many of us inexorably to overeat and gain weight. Yet others seem to remain lean no matter what they do—a topic we’ll return to in the next chapter.
The set point doesn’t just differ by individual; it can change over time in the same person. Most people in affluent nations gain fat over the course of a lifetime, showing that the set point can move upward, gradually increasing the lower limit of our comfortable weight. This malleability explains how a lean nation like the nineteenth-century United States can become dangerously overweight over the course of a few generations, without a significant change in genetic makeup. Our body weight isn’t completely determined by our genes. Just like the temperature set point, the adiposity set point responds to the conditions of our lives.
In 2000, Barry Levin, an obesity and diabetes researcher at Rutgers University, published a paper clearly demonstrating this effect in rats.55 Starting with a genetically diverse strain of rats, he fed them either ordinary rat pellets or a high-calorie palatable diet. On the palatable diet, some of the rats gained weight and fat, while others didn’t. Levin’s team took the rats that had gained weight and restricted their food intake while keeping them on the palatable diet, which caused them to lose weight and fat. So far this is what you might expect, but what they found next is more interesting: When they lifted the calorie restriction, allowing the animals to eat as much as they wanted again, the rats didn’t just resume their gradual upward trajectory of weight gain—they quickly bounced back up to the weight of rats that had been eating an unrestricted palatable diet and gaining weight the entire time. Levin’s findings suggest that there is a certain weight that the lipostat “wants” an animal to maintain, defending it against changes, and that this weight depends both on genetics and on the specific diet the animal is eating.
Levin’s team went further, testing the effects of rotating an obesity susceptible strain of rats between three different diets.56 The first diet was ordinary rat pellets, the second diet was the same palatable diet as the previous experiment, and the third diet was a highly palatable milkshake-like meal-replacement beverage called Ensurefn19 (specifically, the chocolate flavor). As expected, the rats began overeating and gaining weight and fat on the palatable diets. In fact, the rats eating Ensure almost doubled in weight over ten weeks—an impressive feat.
Yet when Levin’s team made the rats switch diets, they found that the rats seemed to defend dramatically different body weights depending on which diet they were currently eating. For example, when they were switched from Ensure to ordinary pellets, their food intake dropped impressively and they rapidly lost weight, until they approximated the weight of animals that had been eating pellets the whole time. When these same animals were switched back to Ensure, they gorged and quickly bounced back up to the weight of animals that had been eating Ensure the whole time. Again, it seemed as if the diets were not just passively causing weight gain but actually changing the set point of the lipostat. Levin ascribed much of this effect to the diet’s palatability, in part because the rats would only overeat and gain weight on chocolate-flavored Ensure—not vanilla or strawberry! fn20
This effect hasn’t been studied as thoroughly in humans, but there are tantalizing clues that it might apply to us as well. Let’s return to the studies we encountered in chapter 3, in which volunteers with obesity lost weight rapidly on an unrestricted bland liquid diet dispensed by a machine through a straw.57 The volunteers were specifically instructed to drink as much of the liquid diet as they needed to feel satisfied, yet once they began the diet, their calorie intake spontaneously dropped because they simply weren’t very hungry (even though lean people on the same regimen drank a normal amount of calories, showing that it wasn’t physically difficult to do so). They lost weight rapidly, yet their starvation response never seemed to kick in. Something about the bland diet was allowing their bodies to feel comfortable at a lower weight, suggesting that just as with Levin’s rats eating plain old rat pellets, the low reward value of the diet may have lowered their adiposity set point.
Five years after the machine-feeding studies, Michel Cabanac, a physiology researcher at Laval University in Canada, published another study that supported and expanded upon these findings.58 Cabanac’s team had a group of volunteers eat an unrestricted bland liquid diet for three weeks, which caused them to spontaneously eat fewer calories and lose just under seven pounds. Then the researchers had a second group of volunteers lose the same amount of weight over the same period of time by deliberately restricting the portion size of their normal diet. Cabanac found that the portion control group developed the expected hunger response to weight loss—but the bland diet group didn’t. He reported that the bland diet volunteers “reduced their intake voluntarily and were always in good spirits,” while the portion control group “had to continually fight off their hunger and would spend the night dreaming of food.” On the bland diet, the starvation response never kicked in. Cabanac concluded that diet palatability influences the set point of the lipostat in humans.
Returning to the brain, we know that there are important connections between the hypothalamus and reward regions such as the ventral striatum, because hunger magnifies food reward. This is encapsulated in the old adage “Hunger is the best sauce.” Yet we don’t know as much about the mechanisms underlying the reverse connection: how food reward might affect the brain regions that determine appetite and adiposity.
RESTRICTING REWARD
High-reward foods tend to increase food intake and adiposity, while lower-reward foods tend to have the opposite effect. This suggests a weight management “secret” you’ll rarely find in a diet book: eat simple food. The reason you’ll rarely find it in a diet book is that, by definition, lower-reward food is not very motivating. It doesn’t get us excited about a diet, and it doesn’t make books fly off the shelves. We want to hear that we can lose weight while eating the most delicious food of our lives, and the weight-loss industry is happy to indulge us. The truth is that there are many ways to lose weight, but all else being equal, a diet that’s lower in reward value will control appetite and reduce adiposity more effectively than one that’s high in reward value. The trick, as with all diets, is sticking with it, because just as the set point can go down, it can go right back up if you return to your former eating habits. And that means designing an eating plan you can live with for the long haul. For most people, a “bland liquid diet” like those I described isn’t a viable long-term solution, but keeping added fats, sugars, salt, and calorie-dense highly rewarding foods to a modest level may be.
We do, however, have enough information to arrive at some practical conclusions. 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. This may be one reason why regularly eating junk food seems to be a fast track to obesity in both animals and humans. 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.
Exercise
ARE THERE OTHER ways to appease the lipostat? Researchers have often noted that people who exercise more frequently gain less weight over time.59 There’s a seemingly straightforward explanation for this: They’re burning more calories, so they remain in energy balance. This is probably at least partially correct, but there may be more to the story, as Barry Levin’s research suggests. His findings show, not surprisingly, that exercise attenuates weight gain in rats when they’re offered a fattening diet.fn21 Yet Levin’s data also reveal that fit rats aren’t just leaner—they actively defend a lower adiposity set point than sedentary rats on the same diet.60 This is actually quite consistent with human studies, in which physically fit people are better able to resist fat gain in the face of overeating.61 It appears that exercise helps keep the lipostat happy at a lower set point.
Yet many people have pointed out that exercise doesn’t work very well as a weight-loss tool in humans, and they have plenty of data to back them up. If you send volunteers home with advice to exercise regularly, most of them hardly lose any weight.62 Superficially, this presents a striking contrast to the rodent studies. However, I’ve gradually come to believe that there’s more to this story than meets the eye. The problem with many of the human studies is that they simply offer people exercise advice, without having any way to enforce the advice, and often without even accurately measuring how much exercise was actually performed.
In contrast, when we only consider studies in which volunteers had to regularly report to a research gym and exercise under supervision—ensuring compliance—a different picture emerges. In these studies, fat loss is often substantial, and it increases with the intensity and duration of the exercise regimen.63 So it appears that many of us in the research world, including myself at one time, may have misjudged exercise: It really does cause fat loss.
But the evidence is more nuanced than it may initially appear. The research of John Blundell, professor of psychobiology at the University of Leeds, shows that not everyone loses the same amount of fat as a result of exercise. Intrigued by earlier observations that people respond differently to exercise, Blundell and colleagues recruited thirty-five overweight and obese sedentary men and women and assigned them to exercise five times per week for twelve weeks.64 Each session was designed to burn 500 Calories and was supervised by the researchers to ensure compliance. At the end of the twelve-week period, the average participant had lost more than eight pounds of fat. However, this average conceals some very interesting information: Changes in adiposity ranged from a loss of twenty-one pounds to a gain of six pounds! To be fair, only one person out of thirty-five gained fat, and we don’t know what else was happening in that person’s life at the time, but it does show that fat gain is possible in the face of a vigorous exercise program. Two others lost less than a pound of fat—a paltry reward for so much effort.
How is it possible to expend 2,500 extra Calories a week yet gain fat? Again, our answer must lie in the energy balance equation we encountered in chapter 1. The only way for adiposity to increase despite increasing calorie expenditure is if calorie intake increases by an even greater amount. And that’s exactly what Blundell’s team observed. When they measured calorie intake in the volunteers, they found that those who lost less weight than expected were inadvertently increasing their calorie intake in response to exercise. This isn’t particularly surprising, since most of us have probably had the experience of “working up an appetite” after playing sports or doing yard work. What’s remarkable is what happened in people who lost as much, or more, weight than expected: They actually decreased their calorie intake in response to the exercise regimen. In the end, about half of the volunteers ate more as a result of the exercise, and half didn’t.
Presumably, this reflects the effects of exercise on the lipostat, as suggested by Levin’s studies in rats. On one hand, exercise depletes the body’s fat reserves and therefore triggers the lipostat to increase appetite. On the other hand, exercise may lower the adiposity set point among people who carry excess fat, reducing appetite and facilitating fat loss. The strength of each of these opposing forces, which varies from person to person, determines the net change in appetite in response to exercise. So while exercise can cause substantial fat loss, it works better for some people than others.
Another fact that’s often overlooked is the difference between weight loss and fat loss. When someone tries to slim down, the goal is not usually to lose weight—it’s specifically to lose fat. It turns out that exercise helps preserve muscle mass during weight loss. Although slow progress on the scale may be frustrating, changes in the mirror and in health as a result of exercise can be better than what the scale suggests.fn22
In the end, the evidence suggests that if you can maintain a high level of physical activity, it will probably help you prevent fat gain, accelerate fat loss, and maintain that loss. But it only works if you actually do it—and even then, the degree of fat loss depends on how effectively your brain compensates for the lost calories by increasing your appetite.
Low-Carb, High-Protein Diets
LOW-CARBOHYDRATE DIETING IS one of the most popular ways to lose weight, and numerous studies suggest that although it’s no miracle obesity cure, it is more effective than a traditional low-fat portion-controlled diet over periods of about a year.65 This is actually a big deal, because it’s a major reversal of the view that’s prevailed for most of the last half century, which is that fat is fattening, and the best way to lose weight is to cut back on fat. In fact, many people report that low-carbohydrate diets help them curb their appetite and cravings, and the research backs this up.66 When people go on a low-carbohydrate diet, their spontaneous calorie intake drops substantially—even though they usually aren’t making any deliberate effort to eat fewer calories.67
Why? As you may have noticed, this effect looks a whole lot like what happens when the adiposity set point goes down. If we take a closer look at the diets of people who eat a low-carbohydrate diet, what we see is that when they reduce their carbohydrate intake, the proportion of protein in the diet tends to go up. As it turns out, amino acids, the building blocks of protein, act directly in the hypothalamus, influencing the lipostat system.68 Although most of the direct evidence comes from rodent studies, a substantial amount of indirect evidence suggests that a high intake of protein may be able to lower the adiposity set point in humans too.
A 2005 study by University of Washington researcher Scott Weigle and colleagues illustrates just how striking this effect can be.69 Weigle’s team started by determining the habitual calorie intake of a group of nineteen volunteers, after which the researchers fed them a high-protein diet (30 percent of calories) for twelve weeks under tightly controlled conditions. On the high-protein diet, the volunteers’ calorie intake spontaneously declined by an average of 441 Calories per day, and their weight dropped by nearly eleven pounds—despite the fact that it wasn’t a weight-loss study and no one had asked them to eat less. As expected, their leptin levels declined as they lost weight—yet the starvation response never seemed to kick in. The effect can’t be attributed to reducing carbohydrate intake, because Weigle’s team increased protein at the expense of fat, not carbohydrate.
Adding to the case is the work of Maastricht University researchers Klaas Westerterp and Margriet Westerterp-Plantenga, which supports the idea that high-protein diets attenuate the starvation response that typically undermines weight loss. Their studies show that people who lose weight by eating a high-protein diet experience less hunger than those who lose weight by other means, and extra protein also largely prevents the reduction of energy expenditure that often accompanies dieting.70 Consistent with this, their 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 that carbohydrate restriction per se isn’t actually the key ingredient in low-carbohydrate diets.fn23,71 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.
The lipostat system Bernard Mohr first stumbled upon in 1839 is a key nonconscious regulator of food intake and body fatness that often drives us to overeat. It helps explain why weight loss is so hard and why our appetites and waistlines react in certain ways to the cues we give them through our food and lifestyle. But we have much left to uncover as we delve deeper into the machinery of the lipostat. In the next chapter, we’ll explore how genetics affects the lipostat, why some people can eat as much as they want and not gain fat, and how a related system in the brain stem affects how many calories you eat at a sitting.
—Stephan Guyenet en "The hungry brain"
