Make Over Your Metabolism—Really!

Make Over Your Metabolism—Really!

To burn more fat, avoid diabetes and keep your heart healthy, get in sync with your internal body clocks (there are more than you think)

by Arlene Weintraub
Photograph: Brian Stauffer

Anyone who has experienced jet lag knows about the body’s circadian clock. Operating on a 24-hour cycle, this cluster of neurons in the brain is stimulated by light and dark and, scientists say, controls the timing of various body processes, such as sleep and digestion. That’s why when we travel overseas we wake up at the wrong time and sometimes even feel ill: Our circadian clock has not yet shifted to the new time zone. But according to the latest research, that familiar clock is just one of many timing mechanisms in the body, and understanding them can be a key to our physical well-being.

These timing mechanisms, called clock genes, exist throughout the organs and tissues of the body and are not linked to the cycles of daylight and darkness. In a 24-hour cycle, they turn on and off at particular moments, governing essential metabolic processes such as the burning of fat. Sometimes they interact with the circadian clock in our brains, but they often operate independently.

In unlocking the mysteries of these genes, scientists are discovering strategies that make it easier for people to lose weight and potentially fend off killer conditions like diabetes and heart disease (mutations in certain clock genes have been linked to insomnia, obesity and an increased risk of cancer). Here are some goals you can achieve, based on what research has established so far.

Goal 1: Slim down faster
Clock-gene research suggests you can drop pounds simply by fiddling with the timing of your meals. For instance, in a Spanish study published last year, dieters who consumed their main meal before 3 pm lost about 5 percent more weight than those who ate later—even though both groups consumed the same number of calories (1,800 a day), says lead researcher Marta Garaulet, PhD, professor of physiology and nutrition at the University of Murcia.

Why would eating early create a -calorie-burning advantage? It has long been known that some of the fat you ingest is used by the body and some of it is stored (typically in the thighs and abdomen). Researchers have now discovered that adipose (body fat) tissue has clock genes that flip on and off in a rhythmic pattern to discard excess fat—but these timekeeping genes shut down as the day wears on, so less fat is broken down and more is stored. It makes sense, then, that dieters who consume big meals late in the day won’t lose as much weight as those who eat earlier. “If you eat at the wrong time, you lessen the probability of breaking down fat stores in your body,” Garaulet says.

Research in Israel also backs the -theory that you can boost weight loss by tapering your calorie intake throughout the day. Scientists at Hebrew University of Jerusalem and Tel Aviv University took two groups of obese women and gave them three meals a day for 12 weeks. All participants consumed the same number of calories, but half the women ate the highest-calorie meal in the morning and the other half at dinnertime. Those who ate a bigger breakfast and a smaller dinner lost more than twice as much weight as the others. “This again proves it’s not just the number of calories you consume that’s important; it’s also when you consume them,” says lead author Oren Froy, PhD, professor at the Institute of Biochemistry, Food Science and Nutrition at Hebrew University.

The advice to eat a big meal early in the day may be particularly useful for women, who, according to the latest research, are not nearly as good as men at metabolizing fat while they’re sleeping. This means women’s bodies are more likely to turn late-night meals into stored pounds. No one knows yet why women are different, says Vincent Cassone, PhD, chair of the department of biology at the University of Kentucky in Lexington.

Goal 2: Reduce the risks of fatty foods
The right timing is especially important for your overall health if you tend to eat a lot of fat, studies with lab animals suggest. Satchidananda Panda, PhD, associate professor in the regulatory biology laboratory at the Salk Institute in La Jolla, California, fed mice a diet in which 60 percent of the calories came from fat—essentially the human equivalent of eating ice cream and butter all day. Half the mice had access to the food for only eight hours a day, while the other half had access to the food 24 hours a day.

The mice in both groups consumed the same daily quantity of calories, but after 100 days, those that chowed down for only eight hours each day weighed a staggering 28 percent less than the round-the-clock eaters. They also had lower cholesterol and blood sugar levels, less liver damage and far better mobility than their heftier counterparts. When the mice fasted during their normal rest period (daytime, because they’re nocturnal), that allowed their clock genes to operate more robustly, Panda says. The fasting improved the efficiency of a gene called cryptochrome, which regulates the production of glucose in the liver. That in turn boosted the performance of two other groups of clock genes. When all these genes work in tandem, the body is better able to control blood sugar, cholesterol and fatty acids, Panda says.

Other researchers have learned that eating fatty meals late in the day has deleterious effects on the heart. In a study that appeared last year in the International Journal of Obesity, scientists at the University of Alabama at Birmingham discovered that the clock genes in mice’s hearts malfunctioned after they were fed high-fat food when they would normally be sleeping. Their clock genes went on and off at the wrong time of day and got knocked out of sync with the brain’s circadian clock.

That’s a problem, because the heart’s internal clock cells are vital to its functioning. “We think that one role of these clocks is to rev up your metabolism when you wake up so the body can generate enough energy for the heart to beat faster and pump more blood while you’re awake,” says Martin Young, PhD, associate professor in the department of medicine at the University of Alabama at Birmingham. “If the clocks go wrong, the body could have a problem making the energy you need.”

Goal 3: Boost the benefits of exercise
Just as eating a big, fat-filled meal late in the day can knock your clocks out of sync, so can exercising at too late an hour. That’s what scientists at the Research Institute for Time Studies at Yamaguchi University in Japan found when they tracked what happened to an athlete’s clock genes as he did two hours of intense exercise starting at 8 pm. The study subject experienced a delay of two to four hours in the normal activity of three clock genes.

Makoto Akashi, one of the researchers, likens the effect of such a delay to suffering from chronic jet lag. “This would lead to sleep and mental disorders and in the long run could increase the risk for metabolic disorders, cardiovascular diseases and cancer,” Akashi says.

Similarly, Garaulet in Spain discovered that rugby players who ran for 25 minutes at 9 pm altered their circadian rhythms in ways that could throw off their normal metabolism. No such changes occurred when they ran at 9 am or when they didn’t run at all, though the morning exercise produced the healthiest circadian rhythms, Garaulet says. The bottom line: Exercising first thing in the morning and eating your biggest meal before 3 pm is the healthiest way to live.

Goal 4: Sleep more healthfully
If you’re the type of person who goes to sleep at 10 pm and gets up at 6 am on workdays, but then sleeps in on weekends, you’re not doing your body any favors. Another team of University of Alabama researchers discovered that if they changed the light-dark cycle on lab mice—meaning they kept the rodents awake during the day, when mice would normally be sleeping—the mice’s hearts reset to the new schedule much more slowly than the circadian clock in their brains did. “The central clock in the mice’s brains reset within one to two days—very fast,” Young says. “But the clock in their hearts took about eight days.”

Such findings, along with discoveries related to the timing of eating and exercise, may explain the high rate of heart disease in people who work odd hours, such as nurses and police officers, Young says. “A shift worker may work four nights and then have three days off,” he says. “That means the clock in the heart never has an opportunity to fully reshift. It’s constantly in a state of flux.”

The potential damage of such a schedule may extend well beyond the heart. In a 2011 Slovenian study, six healthy young men were kept awake for 40 hours straight while researchers tracked the activity of their clock genes with blood samples. The scientists found that two clock genes underperformed and essentially threw the entire circadian system off track. Keeping these two peripheral clock genes in sync is important, because both are tumor suppressors, meaning they help the body fight off cancer.

Can you rearrange your life to please your body clocks? Since your job may dictate when you can sleep and our culture when you eat your main meal, it’s not necessarily easy. But those who have witnessed the benefits of paying attention to circadian rhythms say you should make the effort. Panda at the Salk Institute was so moved by his thin, healthy mice that he stopped eating between 8 pm and 8 am every day, when he knew his clock genes would be less active. Some of his colleagues have done the same, and since then they’ve all lost weight. “I have many people complaining to me that they have to go out and buy new pants,” he says, laughing.

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