Turning On Your Healthy Genes: Genetics in Motion

by Katherine E. Tallmadge
The Washington Post

Okay, it’s not a cure for cancer. But researchers plumbing the human genome have identified genes that play key roles in the killer epidemic of obesity and related diseases.

Researchers have discovered “healthy” genes which, when activated, clear fat and sugar from the blood stream quickly and efficiently. The genes can be turned on by as little as a single bout of exercise. Conversely, being sedentary for a mere 24 hours turns down the genes’ activity.

A growing body of research is giving scientists a better understanding of why a sedentary lifestyle is correlated with so many chronic diseases. These findings clearly demonstrate that people have the ability, with regular exercise, to effectively turn on genes which will allow them to live healthier lives. The findings help explain why if people don’t exercise, obesity and disease will be the likely results.

“A sedentary lifestyle actually prevents the expression of some healthy genes,” said Frank W. Booth, professor of physiology at the University of Missouri Medical School in Columbia at a recent USDA-sponsored conference in Washington.

“Keeping these genes activated may help prevent heart disease and insulin resistance or diabetes,” says Booth. “Higher blood levels of fat and sugar increase a person’s risk for these diseases.”

The two genes are referred to as “metabolic” genes. They respond to exercise very rapidly by making proteins which help transfer the food you eat into your muscles for fuel.

The Lipoprotein Lipase gene is one example. It makes the enzyme lipoprotein lipase (LPL). LPL breaks down the fat in your blood after a meal — called triglycerides — into fatty acids. The fatty acids are then taken up by the muscle and burned as fuel.  But if you haven’t exercised during the preceding 24 hours, and LPL is not present or is present in lower quantities, the triglycerides stay in the blood at higher levels and for longer periods. This could possibly lead to atherosclerosis — clogging and hardening of the arteries — and obesity, because the excess triglycerides get stored in fat cells instead of going into the muscles to be burned as fuel.

In a study reported in the American Journal of Physiology last year, researchers had men use a bicycle with one leg, the sedentary second leg served as the “control” in the experiment. They found LPL increased, and fat uptake doubled in the exercised leg as compared to the unexercised leg.

Similar results were found in other studies reported in the American Journal of Clinical Nutrition and The American Journal of Physiology last year. When men and women ate high fat meals 16 or 17 hours after exercising, clearance of blood triglyceride and very low density lipoprotein, VLDL (a form of “bad” cholesterol) was significantly faster.

High levels of LPL has several benefits. Scientists suspect LPL lowers triglycerides. LPL also lowers VLDL and increases blood levels of “good” cholesterol, called high density lipoprotein (HDL).

In another one-leg cycling study, the blood coming out of the exercised leg’s vein had more HDL than the unexercised leg. Researchers suspect the LPL in the muscle actually produces HDL.

But the positive effects of LPL are fleeting. After a mere 24 hours of being sedentary, fat -clearing slows. After a week without exercise, even in highly trained athletes, fat – clearing rates return to the levels of a chronically sedentary person.

Another example of a “healthy” metabolic gene is GLUT4. After a single bout of exercise, this gene makes the protein, GLUT4. GLUT4 transfers blood sugar to the muscle so it is burned as fuel.

In a study reported in the Journal of Applied Physiology last year, researchers showed that glucose uptake into the skeletal muscle is directly related to GLUT4 protein concentration in exercising human muscle. As GLUT4 levels increase, more blood glucose is taken into the muscle. GLUT4 causes a smaller rise of glucose and insulin after a meal thereby lowering insulin resistance, and probably the likelihood of diabetes.

“Any time you have a rapid removal of glucose and insulin from the blood, you are lowering insulin resistance,” said Booth.

Researchers have known for years that exercise lowers blood glucose and insulin levels, but the underlying biological reasons weren’t understood.  Scientists are getting closer to understanding why exercise makes such a positive difference.

Testing aerobically trained athletes revealed significantly lower blood glucose and insulin levels after a meal and exercise. No surprise there. But when these athletes weren’t allowed to exercise for just 10 days, their blood glucose and insulin levels increased dramatically after meals.  They became more insulin resistant, more diabetic – like. Remarkably, after the sedentary period, all it took was just one exercise bout to return them back to the healthier, exercise levels of blood glucose and insulin.

Researchers see the same effect in obese people. Although obesity increases the risk for insulin resistance and type II diabetes, a study reported in the Annals of Internal Medicine in 1999 showed that cardiovascularly fit obese people with a BMI above 27 cut their diabetes rate in half. The study showed even obese people received an independent effect from exercise.

Experts today believe part of the reason for this improvement is the activation of the GLUT4 gene. The gene responds to exercise very rapidly. An active skeletal muscle needs greater glucose removal from the blood to the muscle for energy or storage to prepare for the next exercise bout.

The activation of the LPL and GLUT4 genes, the researchers surmise, may help explain why people who exercise at least 30 minutes per day experience 30% to 40% less diabetes, heart disease, and stroke.

Of course, the implication of all of this isn’t much comfort to those who hope the genetic revolution will liberate us from the annoying realities of weight control and personal health. The bottom line remains this:

To control your weight and reduce risk for obesity-related diseases, you need to exercise regularly. And if you don’t, you’re increasing that risk.

But now we have proof that it’s true.