Obesity: What Does The Brain Have To Do With It?

Kathryn Berkseth, MD

Obesity has become one of the most serious health problems Americans face today. About one in three adults is obese, and another one of the three is overweight. About one in seven of America’s young people are obese and at increased risk of becoming obese adults. Obesity has been shown to increase the risk of developing many other medical problems including heart disease, stroke, some kinds of cancer and diabetes. As we try to face this problem, a number of questions come to mind.

What causes obesity?

Scientists are trying to better understand why and how obesity occurs, and the answer to this question is more complex than “people just eat too much." Obesity is a disorder of energy balance. We have long known that obesity occurs over an extended period of time when we consume more calories in our foods than we burn in our physical activities and exercise. Now scientists have identified other factors within our bodies and in our environments that contribute to what is called the obesity epidemic.

What makes us want to eat?

Normally, the brain responds to many signals from within the body and from the external environment to help it to know when it is time to eat and when eating should stop. We are all familiar with things in our environment that seem to increase our appetites, such as the smells of food nearby, food advertisements, parties with friends, group meals and even emotional triggers, like stress, which can change our drive to eat.

Through recent scientific research, we are also learning more about hormone signals within the body that affect our appetites and how many calories we burn. Our bodies produce hormones that send signals to our brains telling it about our food needs. Insulin is one of these hormones. Others include leptin, ghrelin and glucagon-like peptide-1 (known as GLP-1). These hormones help to tell the brain how much energy is available from recent meals and how much energy is in long-term storage as fat.

How are these hormones and the brain involved in obesity?

One area of the brain is thought to be among the most important in putting together all the bodily and environmental signals about eating. This area is called the hypothalamus [hi-po-thal-a-mus]. Hormones from the body go to the brain and especially to the hypothalamus to help control hunger and fullness. Each hormone has its own functions. Leptin is produced by fat cells. When energy stores in fat get low, less leptin goes through the blood to the brain, causing the hypothalamus to increase hunger and slow metabolism. Insulin, which comes from the pancreas, tells the brain whether glucose (sugar) is available to be used as energy. Two other important hormones that help to regulate appetite come from the gut. Ghrelin [grel-in] comes mostly from the stomach and acts in the brain to increase hunger. GLP-1 is released from the intestine when food is present and acts in the brain to make us feel full. At any time, the brain is working hard to combine all of these (and many other) signals to help determine how hungry you feel and how much energy your body will burn. Not only do these four hormones affect your sense of appetite, but they also alter the pleasure or sense of reward you experience from food.

What changes occur in appetite-regulating hormones during obesity ?

In obesity, the amount of fat in the body increases. As body fat increases, leptin levels also increase. However, instead of high levels of leptin leading to fullness and decreased appetite, it appears that obese people become resistant to leptin’s effects. In other words, leptin works less and less effectively as body fat increases. This resistance to the effects of leptin may help explain why many obese people have normal or even increased appetite despite having large amounts of stored calories in their bodies in the form of fat.

In contrast to leptin, GLP-1 levels tend to be lower in obese subjects. Because GLP-1 is an important signal of fullness, lower levels of this hormone in obese people may also contribute to continued hunger despite excess body fat. The reasons why obese people become resistant to leptin and have changes in GLP-1 levels are not understood but are active areas that scientists are researching.

Are there visible changes in the brain during obesity?

Yes, scientists have shown that when an animal eats a very high-fat diet and becomes obese, the hypothalamus becomes inflamed. Specialized cells that are known to come to the aid of injured or damaged tissues are found in this inflammation. In addition, when an animal has been on a high-fat diet and has been obese for a long time, some of the cells in the hypothalamus that are involved in telling the brain when the animal is full are lost. Studies suggest that this kind of inflammation in the hypothalamus is also happening in obese people.

There is active research to try to determine what causes these changes, if these changes are reversible when weight is lost, if they can be prevented, and if treatments of these changes in the brain might help control obesity in the future.

What is available now to treat these changes in hormone levels and brain function in obese people?

New drugs are being developed to take advantage of our new understanding of the role of hormones in obesity. These include drugs that simulate the gut hormone GLP-1 (like exenatide [ex-EN-a-tide] and liraglutide [LIR-a-GLU-tide]) that are now being used for the treatment of type 2 diabetes mellitus. Currently, there are no treatments available to reverse leptin resistance or prevent the changes in the hypothalamus, but these are areas of ongoing research.

What can I do about obesity today ?

While scientists and doctors continue to work to better understand what causes obesity and to develop new treatments, there are many things individuals can do now. If you are concerned about your body weight, discuss it with your doctor and get help to develop a nutrition/diet plan that is right for you. Your doctor also can help you understand what kinds of exercise would be safe for you to start. Many people set goals to lose large amounts of weight, but studies show that losing only five to 10 percent of your body weight (10-20 pounds for someone who weighs 200 pounds) helps to lower blood pressure, lower cholesterol and improve blood sugars. By sticking to a nutrition and exercise plan that is customized to your needs, you can improve your overall health and reduce your risk of obesity and obesity-related diseases.

Dr. Kathryn Berkseth is a Senior Fellow in the Division of Endocrinology, Metabolism and Nutrition at the University of Washington in Seattle. She is a graduate of Carleton College and the University of Minnesota Medical School and completed residency in internal medicine at Mayo Clinic in Rochester, MN. She is board certified in Internal Medicine and Endocrinology and is interested in all aspects of clinical endocrinology, particularly the management of obesity and obesity-related diseases. Her research focuses on the relationship between hormones, obesity and the brain.