Weight gain isn't just a number on your bathroom scale.
A new Stanford study has found that the entire body undergoes changes for the worse when people pack on the pounds.
Even just a modest weight gain of about 6 pounds causes bacterial populations to change, immune responses to shift and changes in the molecular pathways associated with heart disease, researchers found.
"Your body is responding to a very stressful event," said lead researcher Michael Snyder, a professor of genetics at Stanford.
But here's the good news: When the weight is lost, the body's systems return to their natural, healthier state.
A paper describing the study as published in Wednesday's issue of the journal Cell Systems.
"The whole body is engaging," Snyder said. Weight gain "is a systemic disease, not just affecting your fat, but affecting your whole body. And luckily, it reverses when you lose it."
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 participants' transcriptome, a collection of molecules that reveal patterns of DNA expression; the proteome, the complete set of proteins that are produced; the microbiome, the microbes that keep us alive; and the genome, or genetic blueprint.
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 - moderate though it was - the participant's underlying biological profiles shifted, too.
"The goal was to characterize what happens during weight gain and loss at a level that no one has ever done before," Snyder said.
The team also wanted to study the underlying molecular shifts in people at risk of diabetes.
"Most studies look at just one little part of something. It's like making a jigsaw puzzle by just looking at the edge pieces," he said. "We are trying to look at the entire puzzle, putting all the pieces together, which lets us see things much better."
The 17-member 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, Yale University, the Royal Institute of Technology, the Chalmers Institute of Technology, the University of Gothenburg and Uppsala University also contributed to the work.
Their analysis revealed a shift in the body's microbiome, the vast army of microbes that protect us against germs, breaks down food to release energy, produce vitamins and perform other tasks.
Microbial species changed with weight gain, the researchers found. For instance, populations of a 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.
Secondly, there was a change in the body's immune responses. Inflammation flared more in normal people than in those with extra pounds, they found.
With weight gain, "inflammation was a little impaired," Snyder said. "The immune system is a bit crippled."
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, said Snyder. While the activated pathway is not causing heart issues, "it is a signal of what's going on."
Snyder's advice: "Don't gain the weight. Exercise, and the food you eat, are absolutely critical."