Featured Research

from universities, journals, and other organizations

Intestinal bacteria drive obesity and metabolic disease in immune-altered mice

Date:
March 8, 2010
Source:
Emory University
Summary:
Mice lacking a gene called TLR5 have an altered ability to recognize and control bacteria in their intestines, leading them to develop obesity and insulin resistance, which is often referred to as "pre-diabetes." The bacteria appear to influence appetite and metabolism rather than how well calories are absorbed. Obesity and insulin resistance can be transferred from TLR5-deficient mice via intestinal bacteria.

New research finds that mice lacking a gene called TLR5 have an altered ability to recognize and control bacteria in their intestines, leading them to develop obesity and insulin resistance.
Credit: iStockphoto

Increased appetite and insulin resistance can be transferred from one mouse to another via intestinal bacteria, according to research being published online by Science magazine.

The finding strengthens the case that intestinal bacteria can contribute to human obesity and metabolic disease, since previous research has shown that intestinal bacterial populations differ between obese and lean humans.

"It has been assumed that the obesity epidemic in the developed world is driven by an increasingly sedentary lifestyle and the abundance of low-cost high-calorie foods," says senior author Andrew Gewirtz, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine. "However, our results suggest that excess caloric consumption is not only a result of undisciplined eating but that intestinal bacteria contribute to changes in appetite and metabolism."

The first author of the paper is Emory faculty member Matam Vijay-Kumar, PhD, who has been studying a mouse strain with an altered immune system. These mice were engineered to lack a gene, Toll-like receptor 5 (TLR5), which helps cells sense the presence of bacteria. TLR5 recognizes flagellin, the main component of the apparatus (flagella) that many bacteria use to propel themselves.

The study began with Emory researcher Jesse Aitken's unexpected observation that TLR5-deficient mice are about 20 percent heavier than regular mice and have elevated triglycerides, cholesterol and blood pressure. They also have mildly elevated blood sugar and increased production of insulin, Vijay-Kumar and Gewirtz found. TLR5-deficient mice tended to consume about 10 percent more food than their regular relatives. When their food was restricted they lost weight but still had a decreased response to insulin (i.e. insulin resistance). When fed a high-fat diet, TLR5-deficient mice gained more weight than regular mice and, moreover, developed full-blown diabetes and fatty liver disease. In short, TLR5-deficient mice exhibit "metabolic syndrome," a cluster of disorders that in humans increases the risk of developing heart disease and diabetes.

Previous research has shown that TLR5 plays a prominent role in controlling bacteria in the intestine. Under certain conditions, many TLR5-deficient mice develop colitis, an inflammatory bowel disease, while the majority of the mice have chronic low-level inflammation.

"The intestine is like a complex community, with good and bad actors," Gewirtz says. "We can think of TLR5 as being like a neighborhood police officer who can distinguish law-abiding residents from potential trouble makers. Take away TLR5, and the safety of the community deteriorates."

Treating TLR5-deficient mice with strong antibiotics, enough to kill most of the bacteria in the intestine, reduces their metabolic abnormalities. This led Gewirtz's team to analyze the composition of the intestinal bacteria of TLR5-deficient mice, collaborating with Ruth Ley at Cornell University.

Ley's earlier research on mice and humans shows that obesity results in more bacteria of the Firmicutes family and less of the Bacteroidetes, which increases the intestine's ability to harvest calories from food. In contrast, TLR5-deficient mice had normal proportions of Firmicutes and Bacteroidetes but differed in the bacterial species that comprised these families.

Importantly, Gewirtz and his team found that transfer of the intestinal bacteria from TLR5-deficient mice to regular mice transferred many of the characteristics of metabolic syndrome including increased appetite, obesity, elevated blood sugar, and insulin resistance.

Humans' intestinal bacterial populations are thought to be acquired at birth from family members and are relatively stable, but they can be influenced by diet and antibiotics.

"Previous research has suggested that bacteria can influence how well energy is absorbed from food, but these findings demonstrate that intestinal bacteria can actually influence appetite," Gewirtz says.

Noting that insulin is known to dampen appetite, he adds: "Even in the absence of colitis, the TLR5-deficient mice seem to have low-level inflammation. We're not yet sure if this inflammation leads to alterations in intestinal bacteria or vice versa, but this shows that once the microbial community changes, it can transfer metabolic abnormalities to other mice. This suggests that it's possible to 'inherit' metabolic syndrome through the environment, rather than genetically. Do obese children get that way because of bad parenting? Maybe bacteria that increase appetite are playing a part."

Gewirtz says his team plans future investigations into variations in the TLR5 gene in humans, and additional studies of what's different about the bacteria in TLR5-deficient mice and how they might influence appetite and metabolism.

The research was supported by the National Institutes of Health and the Crohn's and Colitis Foundation of America.


Story Source:

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


Journal Reference:

  1. M. Vijay-Kumar et al. Altered Gut Microbiota in Toll-Like Receptor-5 (TLR5) Deficient Mice Results in Metabolic Syndrome. Science, 2010;

Cite This Page:

Emory University. "Intestinal bacteria drive obesity and metabolic disease in immune-altered mice." ScienceDaily. ScienceDaily, 8 March 2010. <www.sciencedaily.com/releases/2010/03/100304142232.htm>.
Emory University. (2010, March 8). Intestinal bacteria drive obesity and metabolic disease in immune-altered mice. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2010/03/100304142232.htm
Emory University. "Intestinal bacteria drive obesity and metabolic disease in immune-altered mice." ScienceDaily. www.sciencedaily.com/releases/2010/03/100304142232.htm (accessed April 16, 2014).

Share This



More Plants & Animals News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
In Washington, a Push to Sterilize Stray Cats

In Washington, a Push to Sterilize Stray Cats

AFP (Apr. 14, 2014) To curb the growing numbers of feral cats in the US capital, the Washington Humane Society is encouraging residents to set traps and bring the animals to a sterilization clinic, after which they are released.. Duration: 02:29 Video provided by AFP
Powered by NewsLook.com
After Attack, Officials Kill 5 Bears in Florida

After Attack, Officials Kill 5 Bears in Florida

AP (Apr. 14, 2014) Florida wildlife officials say they have killed five bears following an attack on a woman in a suburban subdivision in central Florida. Forty-five year-old Terri Frana was attacked by a large bear in her driveway Saturday. (April 14) Video provided by AP
Powered by NewsLook.com
Uruguay Opens Its First Cannabis Library

Uruguay Opens Its First Cannabis Library

AFP (Apr. 13, 2014) Uruguay opened its first Cannabis Library in Montevideo on Saturday, where people can come and read books on cannabis or take classes on how to grow the plant or even how to cook with it. Duration: 01:20 Video provided by AFP
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