Nav: Home

Intestinal immune cells play key role in metabolic regulation, cardiovascular health

January 30, 2019

A Massachusetts General Hospital (MGH) research team has identified what appears to be an important checkpoint in dietary metabolism, a group of cells in the small intestine that slow down metabolism, increasing the amount of ingested food that is stored as fat rather than being quickly converted into energy. In the report published in Nature they find that mice lacking these cells can consume diets high in fat and sugar without developing conditions like obesity, diabetes, hypertension and heart disease.

"After you eat, your body can convert energy into heat and burn it quickly or it can convert the food into fat and store it for later use," says Filip Swirski, PhD, of the MGH Center for Systems Biology, senior author of the Nature paper. "We often speak of people who have a 'high metabolism' and seem to be able to eat whatever they want without gaining weight, while others struggle with obesity. These cells, which are known for their function in the immune system, also appear to play an important role in that metabolic choice."

The team's study focused on a protein called integrin β7, which is known to direct immune cells to the gut but not previously to have any influence over metabolism. The MGH team initially found that mice lacking the gene for integrin β7 and fed a normal diet gained equal amounts of weight as did a group of control animals, even though the β7-negative animals ate more food and were equally as active. Metabolic testing indicated that the β7-negative mice converted more food into energy, suggesting they had a higher basal metabolism. They also burned more glucose in brown fat, were more glucose tolerant, had lower triglyceride levels and better fat tolerance than did control mice.

To investigate whether these benefits persisted under nutritional conditions known to induce the metabolic syndrome - a group of symptoms associated with type 2 diabetes and cardiovascular disease - they fed both β7-negative mice and control mice a diet high in fat, sugar and sodium. The β7-negative mice remained lean, glucose tolerant, and did not develop hypertension or other typical results of a high-fat diet. The control mice did become obese, with elevated blood pressure and reduced glucose tolerance.

Experiments with a mouse model genetically programmed to develop elevated cholesterol found that blocking β7 expression in the bone marrow, where immune cells are generated, maintained normal lipid levels in the animals, in spite of their being fed a high-cholesterol diet. Mice with β7-negative marrow excreted more cholesterol, had improved glucose tolerance and were less likely to develop arterial plaques and other cardiovascular risk factors than were animals with normal bone marrow expression of β7.

A search for the cells responsible for β7's metabolic impact revealed that the protein's expression was highest in a group of T cells present in the lining of the small intestine. While β7 guides several types of immune cells to the intestines, only these β7-expressing intraepithelial T cells appear to regulate systemic metabolism. Swirski's team showed they do so by reducing levels of a protein called GLP-1, which normally increases metabolism by stimulating insulin secretion and glucose uptake.

Swirski explained that the metabolism-suppressing role of β7-positive intraepithelial T cells might have developed to prevent starvation under conditions of nutrient scarcity. "At times when the availability of food is uncertain, it would be advantageous to have a system that converts some of the energy ingested with food into fat. But during times of over-nutrition, such a system can backfire and lead to the cardiovascular disease that is so prevalent today," he says.

"Now we have a lot of questions to investigate - exactly how these cells limit the availability of GLP-1, whether people with a higher metabolism have fewer of these cells, how the cells' function may change over the course of a day or a lifetime, and whether blocking these cells can be beneficial in treating obesity, diabetes, hypertension and atherosclerosis." Swirski is an associate professor of Radiology at Harvard Medical School.
-end-
The co-lead authors of the Nature paper are Shun He, PhD, Florian Kahles, MD, and Sara Rattik, all at the MGH Center for Systems Biology. The Swirski lab (@SwirskiLab) also collaborated with Ralph Weissleder, MD, PhD, and Matthias Nahrendorf, MD, MGH Center for Systems Biology; Peter Libby, MD, Brigham and Women's Hospital; Carlos Fernandez-Hernando, PhD, Yale University, and Daniel Drucker, MD, Mount Sinai Hospital, Toronto. Support for the study includes National Institutes of Health grants R35 HL135752, R01 HL128264 and P01 HL131478 and the American Heart Association Established Investigator Award. Swirski is the Patricia and Scott Eston MGH Research Scholar.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2018 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."

Massachusetts General Hospital

Related Diabetes Articles:

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.
Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.
Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#566 Is Your Gut Leaking?
This week we're busting the human gut wide open with Dr. Alessio Fasano from the Center for Celiac Research and Treatment at Massachusetts General Hospital. Join host Anika Hazra for our discussion separating fact from fiction on the controversial topic of leaky gut syndrome. We cover everything from what causes a leaky gut to interpreting the results of a gut microbiome test! Related links: Center for Celiac Research and Treatment website and their YouTube channel
Now Playing: Radiolab

The Flag and the Fury
How do you actually make change in the world? For 126 years, Mississippi has had the Confederate battle flag on their state flag, and they were the last state in the nation where that emblem remained "officially" flying.  A few days ago, that flag came down. A few days before that, it coming down would have seemed impossible. We dive into the story behind this de-flagging: a journey involving a clash of histories, designs, families, and even cheerleading. This show is a collaboration with OSM Audio. Kiese Laymon's memoir Heavy is here. And the Hospitality Flag webpage is here.