Study Suggests Genetic Changes Linked to Weight Gain are Mostly Reversible

An ambitious new study published this month in Cell Systems, however, promises to shed some new light, enumerating for the first time the thousands of changes in genes and various biological systems that may occur after even a small amount of weight gain, and which may — or may not — be reversed if the weight is then dropped.

The findings may help researchers better understand why adding weight causes some people to develop diabetes and other conditions, and also underscore the cumulative health risks of so-called yo-yo dieting.

An international consortium of scientists approached 23 overweight men and women who were already part of a large, continuing study — called an “omics” study in the parlance of researchers — that examines participants’ genomes and microbiomes and generates vast amounts of data about the workings of the body.

But an “omics” study had never looked at the effects of weight change.

After taking blood and other samples from their volunteers, the scientists asked the men and women to overeat.

All of them began the study overweight; about half were insulin-resistant, which is often a precursor to diabetes. For a month, they added on average 880 calories a day to their diets and gained an average of about six pounds.

Scientists found that 318 genes worked differently after most subjects had gained even a little weight.

The scientists then asked the volunteers to cut calories and lose that new weight, which took most of them at least twice as long as the gaining had.

After more samples, the researchers asked participants to keep their weight stable and return after another three months for a final round of tests.

In those tests, the scientists found many biological changes related to weight change.

They found that 318 genes worked differently after most subjects had gained even a little weight.

Some genes were more active, while others were effectively turned off. Many of these genes are thought to be involved in fat metabolism.

The scientists also found multiple new molecular markers in people’s blood after weight gain that can indicate increased inflammation throughout the body and, rather wearisomely, the possible beginnings of cardiomyopathy, or an enlarged heart.

Most of these modifications reverted to their previous normal state once the men and women lost the added weight.

Over all, the results indicate that, after even a relatively small amount of weight gain, “imbalances and shifts occur” throughout the body’s biological systems, says Michael Snyder, chairman of the department of genetics at Stanford University and the study’s senior author.

Even if you later drop those pounds, the shifts “are not reset completely.”

Snyder says that he and his colleagues have larger “omics” studies of weight and health underway.

Results should start arriving later this year.