Even a few extra lbs—6—area ‘stressful event’

Study: Modest weight gain can lead to diabetes, heart disease, bad bacteria

STANFORD >> Weight gain isn’t just a number on your bathroom scale.

A new Stanford study has found that the entire body undergoes microbial, molecular and genetic changes for the worse when people pack on the pounds. When weight is lost, the systems return largely to their original state.

Even just a modest weight gain of about six pounds, researchers found, alters the body’s basic biology — potentially boosting the risk of heart disease and diabetes. Bacterial populations morph. Inflammation patterns shift. The cardiac system undergoes genetic changes.

“Your body is responding to a very stressful event,” said lead researcher Michael Snyder, a professor of genetics at Stanford. The study was published in Wednesday’s issue of the journal Cell Systems. Weight gain “is a systemic disease, not just affecting your fat but affecting your whole body,” Snyder said.

Previous research tended to link obesity to disease in a very general way, warning us that fat is a killer. But technological advances make it possible, for the first time, to record and compute the vast amount of information generated inside a thickening — or thinning — body.

Standing on a scale just offers one metric; a conventional blood test might measure 20 more. But new tools now can track fluctuations in millions of molecules in blood.

“We see the nuts and bolts of what’s happening,” Snyder said.

Trained at the California Institute of Technology, Snyder is a leader in the convergence of fast-moving scientific fields: genomics (the study of one’s DNA), metabolomics (study of metabolism) and proteomics (study of proteins).

In 2012, Snyder made headlines by analyzinghis own blood. A team of 40 other researchers scanned Snyder’s blood, taken 20 different times, to learn more about the dance between

biochemistry and health.

This detailed view could lead to better health care, said Dr. Wendy Scinta, president of the Obesity Medicine Association, based in Denver. While cautioning that the study is small, Scinta said it suggests why yo-yo diets can be harmful. It also could open doors for the role of microbes in helping control weight.

“It is something that we’ve sort of known — and now there is more proof,” Scinta said.

“It’s a landmark paper,” said Leroy Hood, founder of the Institute for Systems Biology, a multidisciplinary institute in Seattle dedicated to examining the interactions between biological information at many different levels. He was not involved in the study.

“Personalized medicine” is expensive but holds great potential, Hood said. “Each individual has to be viewed

in the context of what they are by virtue of their genetics and their lifestyle and environmental exposures.”

The team studied 23 people with body mass indexes of between 25 and 35 kilograms per square meter. A BMI of 25 is on the high-end of normal; a BMI of more than 40 roughly equates to morbid obesity.

About half of the people were insulin-resistant or at risk of diabetes. The other half were insulin-sensitive or able to process insulin normally.

From blood samples, they pooled millions of pieces of information from the participants’ bacteria, proteins and molecules that reveal patterns in how genes express themselves.

Then participants received a high-calorie diet — about 1,000 extra calories per day for men, 750 for women — and after 30 days they had, on average,

tacked on 6 pounds.

“It’s not unlike what a lot of us have just done over the Christmas holiday,” Snyder said. “This is not outside the realm of what normally goes on.”

And with weight gain, the participant’s underlying biological profiles shifted too.

The Stanford research team included experts with Stanford Bio-X, the Stanford Child Health Research Institute, the Stanford Cancer Institute, the Stanford Neurosciences Institute and the Stanford Cardiovascular Institute. Researchers at the Jackson Laboratory for Genomic Medicine and others contributed.

The scientists’ analysis revealed a shift in the body’s microbiome, the vast army of microbes that protect us against germs, break down food to release energy, produce vitamins and perform other tasks. But not all of

the changes were consistent across every participant.

Microbial species changed with weight gain, the researchers found. For instance, populations of bacteria called Akkermansia muciniphila, which is known to protect against insulin resistance, shot up. “This is a trend that could help understand the underlying dynamics that lead to diabetes,” Snyder said.

Secondly, there was a change in the body’s immune responses. The inflammatory pathway is activated in response to shortterm weight gain, the study found. Inflammation is an issue in people with diabetes.

Finally, the molecular pathways associated with heart disease were activated.

There was a shift in gene expression associated with increased risk for a type of heart failure called dilated cardiomyopathy, in which the heart cannot pump blood efficiently to the rest of the body.

This might explain, indirectly, why the risk of heart attack climbs with added weight, Snyder said. While the activated pathway is not causing heart issues, “it is a signal of what’s going on.”

Here’s the good news: When participants lost the weight, almost all of their body’s systems calibrated back to their original states, the study found. However, a small subset of weight-gainassociated shifts in protein and molecule production did persist, even after participants had shed the extra pounds, the study found.

Snyder’s advice: “Don’t gain the weight. Exercise — and the food you eat — are absolutely critical.”