Genetically engineered mice don't get obese (w/Podcast)

May 7, 2009
Genetically engineered mice don't get obese

Enlarge

Mice lacking the L-Fabp gene (left) don't become obese on a high-fat diet like normal mice. But while they remain lean, the L-Fabp mice do develop gallstones at high rates. Credit: Washington University School of Medicine

Obesity and gallstones often go hand in hand. But not in mice developed at Washington University School of Medicine in St. Louis. Even when these mice eat high-fat diets, they don't get fat, but they do develop gallstones. Researchers say the findings offer clues about genetic factors related to gallstones, and they believe better understanding of those factors may one day allow physicians to monitor people at risk and even, perhaps, to intervene before gallstones become a serious problem.

Learning more about susceptibility to gallstones is an important public health issue, particularly in the United States. Between 16 million and 22 million Americans have gallstones, which are deposits of cholesterol or calcium salts that form in the or in the bile ducts. In many cases, people require surgery, and more than half a million undergo operations to treat gallstones and remove the gallbladder each year.

"Gallstones form when cholesterol is secreted in bile from the liver at high concentrations, and that typically happens in patients who are obese, who have diabetes, take estrogens or who have lost a lot of weight very rapidly," says senior investigator Nicholas O. Davidson, M.D., D.Sc., a Washington University gastroenterologist at Barnes-Jewish Hospital. "Since these mice don't become obese, we thought they might be protected against gallstones. But we found that they were dramatically more susceptible."

This video is not supported by your browser at this time.

Mice lacking a fatty acid binding protein do not become obese, but they do develop gallstones. Credit: Washington University School of medicine

The researchers studied a strain of mice without a substance called liver fatty acid (L-Fabp). Davidson's group compared those genetically engineered mice to their healthy, normal littermates. Both groups of mice ate either a standard chow diet or a more typical "Western" diet that provided about 20 percent of its calories in the form of fat and cholesterol.

After two weeks on the Western diet, only one in 17 of the normal mice developed gallstones, but six of the eight mice without L-Fabp had gallstones. Davidson's team reports its findings in the May issue of the Journal of Lipid Research.

Davidson says in addition to risk factors such as diabetes and obesity, these experiments show play a role in gallstone risk. The L-Fabp gene, which both mice and humans have, may be a key to understanding how genes can predispose to cholesterol gallstone formation.

"The L-Fabp gene is located in a part of the mouse genome that appears likely to be involved in genetic susceptibility to gallstones," Davidson says. "We believe it also may be involved in gallstone susceptibility in humans."

He says that although minimally invasive gallbladder surgery has made gallstone problems much less serious than in the past, sometimes the symptoms can be severe and dramatic.

"Patients can develop acute pancreatitis or ascending cholangitis, which occurs when gallstones obstruct the pancreatic or bile duct and become infected," he explains. "Even without those problems, gallstones can cause severe, recurrent abdominal pain in a very large number of people. So better understanding who is susceptible and learning how to safely intervene could be very important for people at risk."

How the L-Fabp protein may be contributing to gallstone formation in the genetically engineered mice is likely to be complex. Davidson believes the problem may be related to abnormal processing of and altered bile metabolism in the small intestine and liver of these genetically engineered mice. The mice also are lean, and he expects that whatever is happening in these mice to produce gallstones will involve complex interactions of other genes that regulate energy utilization and feeding behavior.

Davidson says more studies of the mice lacking L-Fabp may provide scientists with tools that separate obesity from obesity-related problems. For example, prior to this gallstone finding, the team reported L-Fabp deficient mice on a high-fat also develop insulin resistance like their normal littermates.

"That finding demonstrated that although these mice remain lean and have less fat in the liver, they still develop insulin resistance, a problem usually associated with ," Davidson says.

Why the mice don't become obese is not yet known. Davidson says part of the reason may be the mice burn energy more efficiently or they may not eat as much as their normal littermates. He believes the mechanisms likely will take time to sort out.

Davidson's team now is working to determine how L-Fabp operates in the digestive tract. His group is studying mice with tissue-specific deletion of the fatty acid binding protein in either the liver or the small intestine to see how that affects gallstone risk. He also plans to study variations in the human gene to see whether those genetic changes affect the risk of gallstone development.

More information: Xie Y, Newberry EP, Kennedy SM, Luo J, Davidson NO. Increased susceptibility to diet-induced gallstones in liver fatty acid binding protein knockout . Journal of Lipid Research, vol. 50, pp. 977-987, May 1, 2009.

Source: Washington University School of Medicine (news : web)

4.7 /5 (3 votes)  

Filter


Move the slider to adjust rank threshold, so that you can hide some of the comments.


Display comments: newest first

Ashy
May 08, 2009

Rank: 1 / 5 (1)
Only one question: can genetically engineered mice have grandchildren?
ArtflDgr
May 08, 2009

Rank: not rated yet
I find this funny...
because they never put these mice in a more wild situation.

that is, see how they survicve the ups and downs in the real world. after all, humans get fat because humans have starved...

these mice would be weeded out the first generation that didnt have enough to eat.. none of them woudl survive while the slightly fatter ones would.

end of story... making people incapable of surviving bad things that move them from an abstract reality to a real one, would eventually lead to mass deaths when things are not perfect for a time.

and to do this and contemplate it as a way to lower teh variablity i the species so that some dont get fat is not good.

better to perhaps let us have our families traditions and be able to make fun of the unhealthy.

yeah.. it doesnt seem nice, but does letting them get fat or modifying their genetics, and cutting off limbs for diabedes any kinder?

its a sick form of compassion.
Rank 4.7 /5 (3 votes)
Related Stories
Relevant PhysicsForums posts
  • We the immaterial soul
    created8 hours ago
  • Is Everyday Technology Killing Us?
    createdFeb 08, 2012
  • Exercise and weight loss
    createdFeb 08, 2012
  • Why do we have head aches? Our brains can't feel anything.
    createdFeb 07, 2012
  • "The end of diseases" by David Agus, interview from Daily Show with Jon Stewart
    createdFeb 04, 2012
  • Oncolytic adenovirus
    createdFeb 04, 2012
  • More from Physics Forums - Medical Sciences

More news stories

FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice

Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show t ...

Medicine & Health / Neuroscience

created Feb 09, 2012 | popularity 4.9 / 5 (53) | comments 21 | with audio podcast

Green tea found to reduce disability in the elderly

(Medical Xpress) -- A lot of research has been done over the past several years looking into the health benefits of green tea. As a result, scientists have found that regular consumption of the beverage leads ...

Medicine & Health / Health

created Feb 07, 2012 | popularity 4.4 / 5 (14) | comments 11 | with audio podcast report

Teen school drop-outs three times as likely to be on benefits in later life

Teen school drop-outs are almost three times as likely to be on benefits in later life as their peers who complete their schooling, indicates research published online in the Journal of Epidemiology and Community Health.

Medicine & Health / Health

created Feb 06, 2012 | popularity not rated yet | comments 13

To perform with less effort, practice beyond perfection

Whether you are an athlete, a musician or a stroke patient learning to walk again, practice can make perfect, but more practice may make you more efficient, according to a surprising new University of Colorado Boulder study.

Medicine & Health / Neuroscience

created Feb 09, 2012 | popularity 4.4 / 5 (15) | comments 6 | with audio podcast

Anyone can learn to be more inventive, cognitive researcher says

There will always be a wild and unpredictable quality to creativity and invention, says Anthony McCaffrey, a cognitive psychology researcher at the University of Massachusetts Amherst, because an "Aha moment" is rare and ...

Medicine & Health / Psychology & Psychiatry

created Feb 09, 2012 | popularity 4.6 / 5 (11) | comments 5 | with audio podcast


Google might launch Drive for cloud storage soon

(PhysOrg.com) -- Google's next big move, according to the Wall Street Journal, is a cloud storage service called Drive. Hardly first to the plate, Google is simply catching up to introducing its cloud reposi ...

Latin America mining boom clashes with conservation

Latin America is experiencing a mining boom as prices rise fuelled by a hike in global demand, but the region is also being hit by a wave of violent protests, strikes and rallies by environmentalists.

Love a click away in Indonesia's Twitter Republic

He was a geeky kid from Yogyakarta, she a glamorous city girl in Jakarta. In a country with one of the world's most vibrant social networking scenes they fell in love on Twitter.

Europeans protest controversial Internet pact

Tens of thousands of people marched in protests in more than a dozen European cities Saturday against a controversial anti-online piracy pact that critics say could curtail Internet freedom.

Walney offshore wind farm is world's biggest (for now)

(PhysOrg.com) -- The Walney wind farm on the Irish Sea--characterized by high tides, waves and windy weather--officially opened this week. The farm is treated in the press as a very big deal as the Walney ...

Navy to begin tests on electromagnetic railgun prototype launcher

The Office of Naval Research (ONR)'s Electromagnetic (EM) Railgun program will take an important step forward in the coming weeks when the first industry railgun prototype launcher is tested at a facility ...