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Per Linda Carroll
Immune cells in the gut can determine whether our metabolisms are hot or cold, a new study suggests.
Experiments in specially designed mice have found that certain cells in the immune system in the small intestine tend to slow down metabolism and send ingested food to be stored as fat instead of converting it to energy, according to the study published in the journal Nature. Mice designed to lack these immune cells can consume diets high in fat, sugar and salt without developing conditions such as obesity, diabetes, hypertension and heart disease, the researchers report.
The hope, the experts say, is that these findings suggest ways to adjust something in people genetically programmed to have a "frugal" or slow metabolism. Perhaps by increasing the levels of certain substances in the gut, the metabolism can be accelerated to get warmer by allowing people to eat a little more without gaining weight.
"When you eat a meal, your body needs to decide what to do with the energy of the meal," said study co-author Filip Swirski, associate professor at Harvard Medical School and principal investigator at the Massachusetts Center for Systems Biology. General Hospital. "The immune system cells calibrate that decision and essentially put the brakes on a high metabolism."
Swirski and his colleagues began by focusing on a protein, called integrin beta7, which directs the immune cells to the intestine. Rats without the protein gene ingested far more than those with the gene, but did not gain weight, although they were no more active than normal mice.
"They just get hot," Swirski said. "They have a higher basal temperature."
The researchers tried to feed the two groups of rats that were high in fat, sugar and sodium, the type of diet known to induce metabolic syndrome – a constellation of symptoms, including high blood pressure, sugar and cholesterol, associated with a higher risk of heart disease.
Mice without beta7 remained in good condition and did not develop glucose intolerance, which leads to higher than normal levels of blood sugar and high blood pressure.
In contrast, normal mice became obese and developed high blood pressure and reduced glucose tolerance.
The researchers analyzed the impact of this protein in mice vulnerable to the development of high cholesterol and hardening of the arteries. Again, mice that were lacking the beta7 protein were healthier, maintaining normal levels of fat, despite being fed a high-cholesterol diet.
But how was beta7 affecting metabolism?
To answer this question, Swirski and his colleagues focused on certain immune cells known as T-cells in the small intestine.
"This is where we come across GLP-1," a protein that stimulates metabolism, Swirski said.
Swirski and his colleagues found that the T cells they were studying had abundant GLP-1 receptors. Rats with more beta7 receptors, but not GLP-1, had faster metabolisms. This proved that "the crucial cells were T cells expressing the GLP-1 receptor," Swirski said.
Slow metabolism helped survival
Now that researchers have discovered the cells that slow down metabolism, Swirski began to wonder why mice – and humans – would have a system that would slow down metabolism.
One possible reason is how humans evolved to survive food shortages over millions of years. "Having that kind of brake under those conditions would be advantageous for survival," Swirski said. "That would mean that you could store food eaten longer since it was converted to fat to be used if you did not have frequent meals."
This has only become a problem in recent times. "When there is too much nutrition, the system backfires," Swirski said.
The new research may be of great importance to humans, said Dr. Emeran Mayer, a UCLA gastroenterologist, author of "The Mind-Intestine Connection: How Hidden Conversation in Our Bodies Impacts Our Mood, Our Choices, and Our Global Health."
Researchers have shown that the immune system cells in the gut "regulate metabolism, contributing to the development of obesity, metabolic syndrome and cardiovascular disease in the presence of a high-fat, high-sugar diet," Emeran said in an e-mail.
Why Some Do not Gain Weight
Calling the new research "provocative," Dr. Toren Finkel said it can help scientists find new ways to help people fight weight gain. There has long been evidence of a connection between the immune system and obesity, said Finkel, director of the Institute of Aging at the University of Pittsburgh Medical Center.
"The inflammatory response to obesity leads to many of the problems associated with it."
Interestingly, there are already diabetes medications that mimic GLP-1, Finkel noted.
This new insight into immune cell biology and metabolism "is extremely important," said Dr. Michael Blaha, director of clinical research at the Ciccarone Center for the Prevention of Heart Diseases at Johns Hopkins Medicine.
It suggests an explanation as to why some people tend to be overweight and others are resistant to becoming obese. "And you're telling us the story is a lot more complicated than a simple calculation of & calories in & calories," he said.
"For a long time, we have addressed the consequences of obesity – such as high blood pressure and high cholesterol – because we have no way of tackling the causes of obesity," Blaha said. "It would be much better if we could treat the reasons for a disordered metabolism instead of its consequences."