Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Genetically engineered mice don't get obese, but do develop gallstones

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 gallbladder 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."

The researchers studied a strain of mice without a substance called liver fatty acid binding protein (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 genetic factors 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 cholesterol 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 diet 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 obesity," 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.

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

This work was supported by grants from the National Institutes of Health.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's Hospitals. The School of Medicine is one of the leading medical research, teaching, and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's Hospitals, the School of Medicine is linked to BJC HealthCare.

Jim Dryden | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>