Evolutionary gut cell mechanism found to slow down metabolism and increase CVD risk

04 Feb 2019 --- Specific cells in the guts of mice slow down metabolism and can eventually contribute to obesity, diabetes, hypertension and atherosclerosis. These findings, published in Nature, could have important implications for the prevention and treatment of these kinds of metabolic diseases in humans. The energy-saving mechanism evolved over millions of years to provide an advantage to organisms when food was scarce, the researchers note, but it may now be backfiring as food is so abundant.

“With this research, we are connecting the dots between gut metabolic food sensors and cardiovascular disease; and might open new therapeutic avenues to treat patients with a host of related conditions,” says Michelle Olive, Ph.D., Program Officer at the NHLBI Division of Cardiovascular Sciences.

“The biggest surprise [from the findings] is that it is a population of immune cells residing in the gut that modulates metabolism. Immune cells are typically studied for their immune function, and here we find they are highly relevant for metabolic function,” Filip Swirski, Ph.D., an Associate Professor at Harvard Medical School and Massachusetts General Hospital, Boston, tells NutritionInsight.

The cells are called intraepithelial T lymphocytes (or natural IELs) and when they are not present, the researchers discovered, the metabolism of the mice goes into overdrive.

“The mice become metabolically hyperactive and, even when consuming a diet very high in fat and sugar, can resist metabolic diseases such as obesity, hypertension, hypercholesterolemia, diabetes and atherosclerosis,” says Swirski.

However, the presence of IELs limits the availability of a type of hormone, incretin GLP-1, that speeds up metabolism. By limiting GLP-1, the natural IELs, in effect, slows down the body’s metabolism and conserve the energy it gets from food.

“Now with food so abundant, this energy-saving mechanism can backfire and lead to unhealthy outcomes,” explains Swirski.

Swirski’s research could eventually shed light on how to prevent and treat cardiovascular disease and other related ailments in humans. The first step is to determine the number and variations of natural IELs in people and then to answer key questions. Are individuals with low numbers of IELs protected against cardiovascular disease? Could blocking IELs reduce their risks?

“Looking forward, we need to better understand how IELs function in metabolism,” says Swirski. “We also need to know whether therapeutic targeting of IELs in humans can be a treatment for obesity, hypercholesterolemia, diabetes and hypertension.”

Investigating how biological substances, such as hormones or blood molecules, can be used to battle obesity has proved fruitful.

“There are already treatments such as Liraglutide, which stimulate insulin production. Additionally, drugs such as Vedolizumab are used clinically for colitis and Crohn’s. However, Vedolizumab would not be expected to interfere with IELs,” Swirski tells NutritionInsight.

A study published in Nature Communications in November suggested that a protein molecule found in blood, BMP8b, can help treat obesity. Increased levels of BMP8b may promote the functions of “brown” fat which is the kind of fat the body burns for energy. The study was carried out in mice, but researchers are hopeful it could be applied in humans too, perhaps with a drug that increases the levels of BMP8b, in turn, treating obesity more effectively.

Research that sheds light on how to tackle the global, ever-growing issue of obesity is important. Last month, it was found that excess body weight was responsible for roughly 4 percent of cancers worldwide in 2012, and that number is likely to rise, an American Cancer Society peer-reviewed study found.

According to the US report, excess body weight has been steadily rising since the 1970s, and by 2016, nearly 40 percent of adults and 18 percent of children (5 to 19 years old) had excess body weight. This translates to almost two billion adults and 340 million children globally.

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