DIABETES
April 12, 2013

Gastric Surgery Changes Genes, Metabolism

The reduction in calories produced by gastric bypass surgery changes fat metabolism and can end type 2 diabetes.

Gastric bypass surgery helps you lose weight by making you feel full with less food. It can drastically reduce the body weight of obese individuals in a short timeframe.

Now it appears the surgery has an even deeper, more far-reaching effect. It produces genetic changes in fat metabolism and paves the way for more weight loss. It can even put type 2 diabetes in remission.

Over time, the lowered caloric intake from gastric surgery produces genetic alterations that dramatically change a person's metabolism.

The surgery reduces the size of your stomach. It also affects how your stomach and small intestine digest food. Because the food no longer reaches parts of your stomach and small intestine, the surgery prevents your body from absorbing all of the calories and nutrients from the food you eat.

Researchers found that, over time, the lowered caloric intake from gastric surgery produces genetic alterations that dramatically change a person's metabolism. The findings may pave the way for new drugs that mimic this weight-loss-associated control of gene regulation.

"The novelty of our work originates with the finding that DNA methylation is altered by weight loss," said first author, Romain Barrès, of the University of Copenhagen, in a statement.

Only people who had the surgery had changes in gene expression. Obese individuals who did not have gastric bypasses showed no genetic or metabolic differences. The modifications affected chemical markings on two genes that control glucose and fat metabolism (PGC-1alpha and PDK4).

Gastric bypass surgery produced a reduction in caloric intake that brought about changes in how certain genes functioned. This genetic change led in turn to fat being metabolized or broken down more efficiently. This improvement in fat metabolism may be an example of the process by which metabolic syndrome begins, but in reverse.

Metabolic Syndrome is a constellation of factors — high blood pressure, abdominal obesity, higher than average blood sugar, low levels of "good" HDL-cholesterol and high triglycerides — that increases the chance of contracting heart disease, diabetes or stroke.

"…[I]n severely obese people, the levels of specific genes that control how fat is burned and stored in the body are changed to reflect poor metabolic health," senior author Juleen Zierath, of the Karolinska Institute, said in a statement. "After surgery, the levels of these genes are restored to a healthy state, which mirrors weight loss and coincides with overall improvement in metabolism."

The findings provide an example of how the environment — in this case overeating — can affect our genes. So, as people gain weight, they may slowly change the genes that control their metabolism and begin the cycle of weight gain seen in so many adults as they age. You really can't gain weight by simply looking at a cookie, but eventually and with enough cookies, your body's metabolism could slow to the point where it comes close.

The study is published online in Cell Reports.

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