KATHLEEN A. PAGE, assistant professor, Keck School of Medicine of USC, and ROBERT S. SHERWIN, professor of medicine, Yale University.
This op-ed originally appeared in the New York Times on April 28.
Imagine that, instead of this article, you were staring at a plate of freshly baked chocolate chip cookies. The mere sight and smell of them would likely make your mouth water. The first bite would be enough to wake up brain areas that control reward, pleasure and emotion — and perhaps trigger memories of when you tasted cookies like these as a child.
That first bite would also stimulate hormones signaling your brain that fuel was available. The brain would integrate these diverse messages with information from your surroundings and make a decision as to what to do next: keep on chewing, gobble down the cookie and grab another, or walk away.
Studying the complex brain response to such sweet temptations has offered clues as to how we might one day control a profound health problem in the country: the obesity epidemic.
The answer may partly lie in a primitive brain region called the hypothalamus. The hypothalamus, which monitors the body’s available energy supply, is at the center of the brain’s snack-food signal processing. It keeps track of how much long-term energy is stored in fat by detecting levels of the fat-derived hormone leptin — and it also monitors the body’s levels of blood glucose, minute-to-minute, along with other metabolic fuels and hormones that influence satiety. When you eat a cookie, the hypothalamus sends out signals that make you less hungry. Conversely, when food is restricted, the hypothalamus sends signals that increase your desire to ingest high-calorie foods. The hypothalamus is also wired to other brain areas that control taste, reward, memory, emotion and higher-level decision making. These brain regions form an integrated circuit that was designed to control the drive to eat.
With sophisticated brain-imaging techniques, we can now even see how our brains respond to specific nutrients (glucose, for example) and environmental stimuli (like the sight of food). Our research team, for example, recently conducted a study to see if the human brain responds in different ways to consumption of two types of simple sugar: glucose and fructose.
Glucose is a critical energy source for our body, particularly the brain. Even tiny changes in blood glucose can be detected by specialized glucose-sensing nerve cells in the hypothalamus. The hypothalamus’s exquisite sensitivity to glucose is especially important because the brain requires a continuous supply of glucose to meet its high-energy needs.
Fructose, a close relative of glucose, molecularly speaking, has the same number of calories but is sweeter than its cousin. Unlike glucose, though, fructose is almost entirely removed from the blood by the liver. Thus, very little of it actually reaches the brain.
The notion that these two sugars affect the brain differently is supported by animal studies. When glucose and fructose are injected directly into the brains of mice they have different effects: glucose blunts hunger signals, whereas fructose stimulates them.
We set out to see if the brains in healthy people would likewise respond differently to these two types of sugar. They did. Blood flow and activity in brain areas controlling appetite, emotion and reward decreased after consuming a drink with glucose, and participants reported greater feelings of fullness. In contrast, after drinking fructose, the brain appetite and reward areas continued to stay active, and participants did not report feeling full.
People don’t typically drink glucose and fructose separately; they are generally found together in foods and beverages. Table sugar is made of 50 percent glucose and 50 percent fructose molecules bound together. High-fructose corn syrup is made of unbound glucose and fructose molecules, usually in a ratio of 45 percent glucose to 55 percent fructose. We don’t yet know whether table sugar and high-fructose corn syrup affect the brain differently, or if they have different effects on body weight over time.
In today’s food-rich environment, we are surrounded with tantalizing food advertisements that sometimes stimulate eating, even in the absence of hunger. Brain imaging studies have shown us why. Pictures of mouthwatering foods can activate brain-reward pathways and stimulate the urge to eat — a response that is often countered by simultaneous suppression signals from “executive control” centers elsewhere in the brain. In obese individuals, though, the ability to suppress the initial brain-reward signals is often impaired. Thus, biological changes in the brain’s capacity to control our drive to eat might serve to perpetuate obesity.
Our brains were designed for a time when food was scarce and starvation was a common cause of death. While too much hunger remains in modern times, most people in the United States face a challenge opposite to what our distant ancestors faced. Natural selection has not wired us for a scenario in which food is abundant, relatively inexpensive and often high in calories.
Tackling this problem won’t be easy. But if we’re going to stop obesity in its tracks, we first need to understand how our brains influence what we eat.