(This article was first printed in the Special Health Report from Harvard Medical School “Weigh Less, Live Longer: Strategies for Successful Weight Loss.” For more information or to order, visit www.health.harvard.edu/WL.)
Everyone knows some people who can eat ice cream, cake, and whatever else they want and still not gain weight. At the other extreme are people who seem to gain weight no matter how little they eat. Why? What allows one person to remain thin without effort but demands that another struggle to avoid gaining weight or regaining the pounds he or she has lost previously?
On a very simple level, your weight depends on the number of calories you consume, how many of those calories you store, and how many you burn up. But each of these factors is influenced by a combination of genes and environment. Both can affect your physiology (such as how fast you burn calories) as well as your behavior (the types of foods you choose to eat, for instance). The interplay between all these factors begins at the moment of your conception and continues throughout your life.
The calorie equation
The balance of calories stored and burned depends on your genetic makeup, your level of physical activity, and your resting energy expenditure (the number of calories your body burns while at rest). If you consistently burn all of the calories that you consume in the course of a day, you will maintain your weight. If you consume more energy (calories) than you expend, you will gain weight.
Excess calories are stored throughout your body as fat. Your body stores this fat within specialized fat cells (adipose tissue) — either by enlarging fat cells, which are always present in the body, or by creating more of them. If you decrease your food intake and consume fewer calories than you burn up, or if you exercise more and burn up more calories, your body will reduce some of your fat stores. When this happens, fat cells shrink, along with your waistline.
To date, more than 400 different genes have been implicated in the development of overweight or obesity, although only a handful appear to be major players. Genes contribute to obesity in many ways, by affecting appetite, satiety (the sense of fullness), metabolism, food cravings, body-fat distribution, and the tendency to use eating as a way to cope with stress.
A 2006 report in Science that studied more than 900 people showed that those who have two copies of a specific gene variant (called Insig-2) were 22% more likely to have a BMI higher than 30. Researchers believe the gene variant affects the regulation of another gene involved in fat production. In follow-up studies of more than 9,000 people (including people with Western European ancestry, African Americans, and children), they found that about 10% carried two copies of the gene variant.
In another 2006 study, published in the Proceedings of the National Academy of Sciences, researchers studied the activity levels of three different genes in fat samples from people who were normal weight, overweight, or obese. They took fat samples from around the participants’ internal organs and under their skin and found different levels of activity (known as gene expression) in the different samples. In overweight people, increased expression of two of the genes correlated with a tendency to be “apple-shaped.” These and related studies have helped researchers better understand how and why obesity occurs. They may also spur the development of new weight-loss treatments.
The strength of the genetic influence on weight disorders varies quite a bit from person to person. Research suggests that for some people, genes account for just 25% of the predisposition to be overweight, while for others the genetic influence is as high as 70% to 80%. Having a rough idea of how large a role genes play in your weight may be helpful in terms of treating your weight problems.
How much of your weight depends on your genes?
Genes are probably a significant contributor to your obesity if you have most or all of the following characteristics:
You have been overweight for much of your life.
One or both of your parents or several other blood relatives are significantly overweight. If both of your parents have obesity, your likelihood of developing obesity is as high as 80%.
You can’t lose weight even when you increase your physical activity and stick to a low-calorie diet for many months.
Genes are probably a lower contributor for you if you have most or all of the following characteristics:
You are strongly influenced by the availability of food.
You are moderately overweight, but you can lose weight when you follow a reasonable diet and exercise program.
You regain lost weight during the holiday season, after changing your eating or exercise habits, or at times when you experience psychological or social problems.
These circumstances suggest that you have a genetic predisposition to be heavy, but it’s not so great that you can’t overcome it with some effort.
At the other end of the spectrum, you can assume that your genetic predisposition to obesity is modest if your weight is normal and doesn’t increase even when you regularly indulge in high-calorie foods and rarely exercise.
People with only a moderate genetic predisposition to be overweight have a good chance of losing weight on their own by eating fewer calories and getting more vigorous exercise more often. These people are more likely to be able to maintain this lower weight.
What are thrifty genes?
When the prey escaped or the crops failed, how did our ancestors survive? Those who could store body fat to live off during the lean times lived, and those who couldn’t, perished. This evolutionary adaptation explains why most modern humans — about 85% of us — carry so-called thrifty genes, which help us conserve energy and store fat. Today, of course, these thrifty genes are a curse rather than a blessing. Not only is food readily available to us nearly around the clock, we don’t even have to hunt or harvest it!
In contrast, people with a strong genetic predisposition to obesity may not be able to lose weight with the usual forms of diet and exercise therapy. Even if they lose weight, they are less likely to maintain the weight loss. For people with a very strong genetic predisposition, sheer willpower is ineffective in counteracting their tendency to be overweight. Typically, these people can maintain weight loss only under a doctor’s guidance. They are also the most likely to require weight-loss drugs or surgery.
The prevalence of obesity among adults in the United States has been rising since the 1970s (see Figure 1). Genes alone cannot possibly explain such a rapid rise. Although the genetic predisposition to be overweight varies widely from person to person, the rise in body mass index appears to be nearly universal, cutting across all demographic groups. These findings underscore the importance of changes in our environment that contribute to the epidemic of overweight and obesity.
Figure 1: Trends in adult weight
Percent of adults ages 20–74* who were at a healthy weight, overweight, or obese†
*Data are age-adjusted to the 2000 U.S. standard population.
†Healthy weight, body mass index (BMI) = 18.5–24; overweight, BMI = 25–29; obese, BMI ≥30.
Sources: National Health and Nutrition Examination Survey (National Center for Health Statistics); Cancer Trends Progress Report — 2005 Update (National Cancer Institute, 2005).
Genetic factors are the forces inside you that help you gain weight and stay overweight; environmental factors are the outside forces that contribute to these problems. They encompass anything in our environment that makes us more likely to eat too much or exercise too little. Taken together, experts think that environmental factors are the driving force for the dramatic increase in obesity.
Environmental influences come into play very early, even before you’re born. Researchers sometimes call these in-utero exposures “fetal programming.” Babies of mothers who smoked during pregnancy are more likely to become overweight than those whose mothers didn’t smoke. The same is true for babies born to mothers who had diabetes. Researchers believe these conditions may somehow alter the growing baby’s metabolism in ways that show up later in life.
After birth, babies who are breast-fed for more than three months are less likely to have obesity as adolescents compared with infants who are breast-fed for less than three months.
Childhood habits often stick with people for the rest of their lives. Kids who drink sugary sodas and eat high-calorie, processed foods develop a taste for these products and continue eating them as adults, which tends to promote weight gain. Likewise, kids who watch television and play video games instead of being active may be programming themselves for a sedentary future.
Many features of modern life promote weight gain. In short, today’s “obesogenic” environment encourages us to eat more and exercise less. And there’s growing evidence that broader aspects of the way we live — such as how much we sleep, our stress levels, and other psychological factors — can affect weight as well.
The food factor
According to the Centers for Disease Control and Prevention (CDC), Americans are eating more calories on average than they did in the 1970s. Between 1971 and 2000, the average man added 168 calories to his daily fare, while the average woman added 335 calories a day. What’s driving this trend? Experts say it’s a combination of increased availability, bigger portions, and more high-calorie foods.
Practically everywhere we go — shopping centers, sports stadiums, movie theaters — food is readily available. You can buy snacks or meals at roadside rest stops, 24-hour convenience stores, even gyms and health clubs. Americans are spending far more on foods eaten out of the home: In 1970, we spent 27% of our food budget on away-from-home food; by 2006, that percentage had risen to 46%.
In the 1950s, fast-food restaurants offered one portion size. Today, portion sizes have ballooned (see Figure 2), a trend that has spilled over into many other foods, from cookies and popcorn to sandwiches and steaks. A typical serving of French fries from McDonald’s contains three times more calories than when the franchise began. A single “super-sized” meal may contain 1,500–2,000 calories — all the calories that most people need for an entire day. And research shows that people will often eat what’s in front of them, even if they’re already full.
Figure 2: Portion inflation
Portion sizes for foods commonly consumed outside the home have increased over the years, and many experts believe this has contributed to overweight and obesity. Consider a typical fast-food meal that consists of a hamburger, French fries, and a soda. In 1955, consumers were offered only one portion size. Today they can select from multiple portion sizes. The chart above shows how all these portions compare, adjusting for size inflation over the years.
Based on data from the Journal of the American Dietetic Association, February 2003, pp. 231–34.
Not surprisingly, we’re also eating more high-calorie foods (especially salty snacks, soft drinks, and pizza), which are much more readily available than lower-calorie choices like salads and whole fruits. Fat isn’t necessarily the problem; in fact, research shows that the fat content of our diet has actually gone down since the early 1980s. But many low-fat foods are very high in calories because they contain large amounts of sugar to improve their taste and palatability. In fact, many low-fat foods are actually higher in calories than foods that are not low fat.
In one year, the average American adult eats 40 pounds of white bread, 41 pounds of potatoes, 30 pounds of cheese, and 77 pounds of added fats (butter, lard, and cooking oil), and washes it all down with 52 gallons of soda. True, vegetable consumption has risen by about 12% since 1990 — but two-thirds of these vegetables take the form of potatoes (including chips, fries, and mashed potato), iceberg lettuce, and other low-nutrient choices.
In all, the Department of Agriculture reports that food consumption rose by 8%, or about 140 pounds per person per year, during the 1990s. Our nation produces 50% more food than we need, and the food industry spends $30 billion a year to be sure it does not go to waste. It works: In 2001, Americans spent $110 billion on fast food, up nearly twentyfold in just three decades.
The exercise equation
The government’s current recommendations for exercise call for an hour of moderate to vigorous exercise a day. But fewer than 25% of Americans meet that goal. On the other hand, more people are exercising than in the late 1980s. According to a 2004 CDC report, the percentage of people who say they do no leisure-time physical activity (such as walking, golfing, or gardening) dropped from a high of 32% in 1989 to 25% in 2002.
Our daily lives don’t offer many opportunities for activity. Children don’t exercise as much in school, often because of cutbacks in physical education classes. Many people drive to work and spend much of the day sitting at a computer terminal. Because we work long hours, we have trouble finding the time to go to the gym, play a sport, or exercise in other ways.
Instead of walking to local shops and toting shopping bags, we drive to one-stop megastores, where we park close to the entrance, wheel our purchases in a shopping cart, and drive home. The widespread use of vacuum cleaners, dishwashers, leaf blowers, and a host of other appliances takes nearly all the physical effort out of daily chores.
The trouble with TV: Sedentary snacking
The average American watches about four hours of television per day, a habit that’s been linked to overweight or obesity in a number of studies. Data from the National Health and Nutrition Examination Survey, a long-term study monitoring the health of American adults, revealed that people with overweight and obesity spend more time watching television and playing video games than people of normal weight. Watching television more than two hours a day also raises the risk of overweight in children, even in those as young as three years old.
Part of the problem may be that people are watching television instead of exercising or doing other activities that burn more calories (watching TV burns only slightly more calories than sleeping, and less than other sedentary pursuits such as sewing or reading). But food advertisements also may play a significant role. The average hour-long TV show features about 11 food and beverage commercials, which encourage people to eat. And studies show that eating food in front of the TV stimulates people to eat more calories, and particularly more calories from fat. In fact, a study that limited the amount of TV kids watched demonstrated that this practice helped them lose weight — but not because they became more active when they weren’t watching TV. The difference was that the children ate more snacks when they were watching television than when doing other activities, even sedentary ones.
Stress and related issues
Obesity experts now believe that a number of different aspects of American society may conspire to promote weight gain. Stress is a common thread intertwining these factors. For example, these days it’s commonplace to work long hours and take shorter or less frequent vacations. In many families, both parents work, which makes it harder to find time for families to shop, prepare, and eat healthy foods together. Round-the-clock TV news means we hear more frequent reports of child abductions and random violent acts. This does more than increase stress levels; it also makes parents more reluctant to allow children to ride their bikes to the park to play. Parents end up driving kids to play dates and structured activities, which means less activity for the kids and more stress for parents.Time pressures — whether for school, work, or family obligations — often lead people to eat on the run and to sacrifice sleep, both of which can contribute to weight gain.
Some researchers also think that the very act of eating irregularly and on the run may contribute to obesity. Neurological evidence indicates that the brain’s biological clock — the pacemaker that controls numerous other daily rhythms in our bodies — may also help to regulate hunger and satiety signals. Ideally, these signals should keep our weight steady. They should prompt us to eat when our body fat falls below a certain level or when we need more body fat (during pregnancy, for example), and they should tell us when we feel satiated and should stop eating. Close connections between the brain’s pacemaker and the appetite control center in the hypothalamus suggest that hunger and satiety are affected by temporal cues. Irregular eating patterns may disrupt the effectiveness of these cues in a way that promotes obesity.
Similarly, research shows that the less you sleep, the more likely you are to gain weight. Lack of sufficient sleep tends to disrupt hormones that control hunger and appetite. In a 2004 study of more than 1,000 volunteers, researchers found that people who slept less than eight hours a night had higher levels of body fat than those who slept more, and the people who slept the fewest hours weighed the most.
Stress and lack of sleep are closely connected to psychological well-being, which can also affect diet and appetite, as anyone who’s ever gorged on cookies or potato chips when feeling anxious or sad can attest. Studies have demonstrated that some people eat more when affected by depression, anxiety, or other emotional disorders. In turn, overweight and obesity themselves can promote emotional disorders: If you repeatedly try to lose weight and fail, or if you succeed in losing weight only to gain it all back, the struggle can cause tremendous frustration over time, which can cause or worsen anxiety and depression. A cycle develops that leads to greater and greater obesity, associated with increasingly severe emotional difficulties.
A widespread problem
Sixty percent of adults in the U.S.
One-third of American adults have obesity
Other causes of obesity
Clearly, our responses to today’s obesity-promoting environment, in tandem with genetic influences, are the most significant causes of overweight and obesity. But in some people, drug side effects, illnesses, and genetic disorders can also play a role.
Drug side effects
Several prescription drugs can cause weight gain as a side effect by increasing appetite or slowing metabolism. These include corticosteroids such as hydrocortisone (used for a variety of conditions to reduce inflammation); estrogen and progesterone (used in oral contraceptives); anticonvulsants such as valproic acid (Depakote, others); certain anticancer medications; and drugs such as olanzapine (Zyprexa), haloperidol (Haldol), lithium (Eskalith, Lithobid), and clozapine (Clozaril), which are used to treat psychiatric conditions.
Paradoxically, weight gain can also be a side effect of some drugs used to treat conditions that result from obesity itself. Among these drugs are insulin and glyburide (DiaBeta and others); these are treatments for diabetes, which is common among people with weight disorders. Several antidepressants may cause patients to put on weight, including tricyclic antidepressants such as imipramine (Tofranil) or desipramine (Norpramin, Pertofrane), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRIs) such as paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), fluvoxamine (Luvox), and fluoxetine (Prozac).
When used to treat depression, SSRIs may cause weight loss initially, but within six months of treatment they can induce weight gain in a significant number of patients. On the other hand, sibutramine (Meridia), another drug that stimulates serotonin (like the SSRIs), is an appetite suppressant that’s used to promote weight loss. And in a small number of patients, SSRIs such as Prozac actually cause weight loss, making them useful as a therapy for weight disorders. Much more needs to be learned in this area; the relationship between weight regulation and serotonin (a key chemical communicator in the brain and elsewhere in the body) is obviously complex.
Illnesses that affect weight
A few illnesses that are characterized by an imbalance or an abnormality in your endocrine glands can also affect your weight. These include hypothyroidism (an underactive thyroid), polycystic ovarian syndrome, and certain unusual tumors of the pituitary gland, adrenal glands, or the pancreas. However, in the vast majority of people, these illnesses are not responsible for weight gain. Most are extremely rare. Hypothyroidism, which is the most common, is seldom the main reason for overweight or obesity. Treatment with thyroid hormone, while medically necessary, does not usually cause a significant weight reduction.
Obesity is also a symptom of some rare and complex disorders caused by genetic defects. These obesity syndromes usually appear in early childhood and are tied to several additional medical problems. One such disorder is Prader-Willi syndrome, a form of obesity associated with mild mental retardation that occurs in about 1 in 25,000 people and has been traced to abnormalities in a group of genes on chromosome 15. People with this disorder are unusually short and have primarily upper-body obesity. A less common disorder, Bardet-Biedl syndrome, is similar to Prader-Willi syndrome, but is caused by abnormalities in different genes. Several other rare genetic syndromes cause obesity, but account for only a tiny fraction of all weight disorders.
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