Featured Research

from universities, journals, and other organizations

Adding intestinal enzyme to diets of mice appears to prevent, treat metabolic syndrome

Date:
April 8, 2013
Source:
Massachusetts General Hospital
Summary:
Feeding an intestinal enzyme to mice kept on a high-fat diet appears to prevent the development of metabolic syndrome -- a group of symptoms associated with type 2 diabetes, cardiovascular disease and fatty liver -- and to reduce symptoms in mice that already had the condition.

Feeding an intestinal enzyme to mice kept on a high-fat diet appears to prevent the development of metabolic syndrome -- a group of symptoms associated with type 2 diabetes, cardiovascular disease and fatty liver -- and to reduce symptoms in mice that already had the condition.

In their report published online in Proceedings of the National Academy of Sciences (PNAS) Early Edition, Massachusetts General Hospital (MGH) investigators describe how dietary supplementation with intestinal alkaline phosphatase (IAP) reduced the inflammation believed to underlie metabolic syndrome by blocking a toxic molecule found on the surface of many bacteria.

"For the first time we are targeting production of inflammatory factors in the intestinal tract to prevent the systemic problem of the metabolic syndrome," says Richard Hodin, MD, of the MGH Department of Surgery, the study's senior author. "Animal studies have shown the gut to be the likely source of these factors, and we have previously shown in laboratory studies that IAP can block their activity. There are human studies that correlate low-grade systemic inflammation with the metabolic syndrome, so we expect that IAP's ability to interfere with the process will apply to humans as well."

Encompassing symptoms including obesity, glucose intolerance, insulin resistance, hypertension and lipid abnormalities, metabolic syndrome affects more than one-third of the U.S. population and significantly increases the risk for cardiovascular disease and type 2 diabetes. A possible contributor to metabolic syndrome is increased blood levels of lipopolysaccharide (LPS), a molecule found on the surface of many gut bacteria and responsible for their toxic effects when it passes through the intestinal wall into the systemic circulation. A persistent increase in circulating LPS, a condition called endotoxemia, causes low-grade inflammation -- a primary aspect of metabolic syndrome -- throughout the body. LPS is known to bind to fat, and several studies have shown that a high-fat diet raises systemic LPS levels in animals and humans, increasing both intestinal inflammation and the permeability of the intestinal wall, allowing additional LPS to pass into the bloodstream.

Previous work in Hodin's lab showed that IAP, which is produced by cells lining the small intestine, can block the action of LPS, leading to the hypothesis that the enzyme could help prevent the systemic inflammation associated with a high-fat diet. In a series of experiments described in the current study, the investigators showed the following:

  • mice in which IAP expression was either knocked out or suppressed developed endotoxemia, overexpression of inflammatory factors and symptoms of metabolic syndrome;
  • feeding IAP to mice on a high-fat diet prevented weight gain and fat accumulation and reduced development of metabolic syndrome;
  • feeding IAP to mice that had developed metabolic syndrome as a result of a high-fat diet, reduced endotoxemia, inflammatory factors and symptoms such as glucose intolerance;
  • feeding IAP to mice on a low-fat diet slightly improved glucose metabolism but significantly improved lipid metabolism.

The researchers note that IAP is naturally found in an environment containing many bacterial factors that induce inflammation -- suggesting that it may suppress the activity of additional factors -- and that several related enzymes should be investigated for shared protective abilities.

"While our findings clearly predict that IAP supplementation could have the same effect in human patients, future studies are required to test this directly," explains Hodin, a professor of Surgery at Harvard Medical School (HMS). "We need a formulation of the enzyme that can be safely given to humans -- something we are working to develop -- which we then can test as a prevention or treatment for metabolic syndrome, a contributor to the number one cause of patient death in this country."

Mahdu Malo, PhD, MBBS, of the MGH Department of Surgery, an assistant professor of Surgery at HMS, is corresponding author of the PNAS Early Edition report and was instrumental in the development of the study concept along with Hodin. Kanakaraju Kaliannan, MD; Sulaiman R. Hamarneh, MBBS; and Konstantinos P. Economopoulos, MD -- all of MGH Surgery -- are co-lead authors. This work was supported by National Institutes of Health grants R01DK050623, R01DK047186 and 2P30 DK43351, the MGH Department of Surgery, and the Bill and Melinda Gates Foundation.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. K. Kaliannan, S. R. Hamarneh, K. P. Economopoulos, S. Nasrin Alam, O. Moaven, P. Patel, N. S. Malo, M. Ray, S. M. Abtahi, N. Muhammad, A. Raychowdhury, A. Teshager, M. M. R. Mohamed, A. K. Moss, R. Ahmed, S. Hakimian, S. Narisawa, J. L. Millan, E. Hohmann, H. S. Warren, A. K. Bhan, M. S. Malo, R. A. Hodin. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1220180110

Cite This Page:

Massachusetts General Hospital. "Adding intestinal enzyme to diets of mice appears to prevent, treat metabolic syndrome." ScienceDaily. ScienceDaily, 8 April 2013. <www.sciencedaily.com/releases/2013/04/130408152902.htm>.
Massachusetts General Hospital. (2013, April 8). Adding intestinal enzyme to diets of mice appears to prevent, treat metabolic syndrome. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2013/04/130408152902.htm
Massachusetts General Hospital. "Adding intestinal enzyme to diets of mice appears to prevent, treat metabolic syndrome." ScienceDaily. www.sciencedaily.com/releases/2013/04/130408152902.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins