In obesity, a micro-RNA causes metabolic problems

University of Illinois molecular and integrative physiology professor Jongsook Kim Kemper and her colleagues were able to reverse some of the metabolic problems associated with obesity in mice by targeting a micro-RNA. Credit: L. Brian Stauffer

Scientists have identified a key molecular player in a chain of events in the body that can lead to fatty liver disease, Type II diabetes and other metabolic abnormalities associated with obesity. By blocking this molecule, the researchers were able to reverse some of the pathology it caused in obese mice.

Their findings appear in the Proceedings of the National Academy of Sciences.

MiR-34a (pronounced MEER-34a), a micro-RNA, occurs at higher than normal levels in the livers of obese animals and in human patients with . In the new study, researchers discovered that miR-34a gums up production of a protein receptor, called beta-Klotho, needed for metabolic signaling in the liver. This hinders normal , glycogen and and other metabolic activities.

In response to signals from the small intestine, beta-Klotho contributes to normal liver function after a meal, said University of Illinois molecular and integrative physiology professor Jongsook Kim Kemper, who led the study. But in obesity, levels of miR-34a surge much higher than normal, resulting in abnormally low levels of beta-Klotho.

"The downstream effect is more glucose in the blood, more fat in the liver," she said.

The effects are dramatic. Slices of from obese mice are laden with fat, whereas normal mice have minimal amounts of fat in their livers.

The researchers used a complementary strand of RNA (called antisense RNA) to neutralize miR-34a in obese mice. This therapeutic approach improved "metabolic outcomes, including decreased liver fat and improved glucose level in the blood," Kemper said.

More information: "Aberrantly Elevated miR-34a in Obesity Attenuates Hepatic Responses to FGF19 by Targeting a Membrane Co-Receptor β-Klotho," Proceedings of the National Academy of Sciences, 2012. www.pnas.org/content/early/201… /1205951109.abstract

Related Stories

Secreted protein sends signal that fat is on the way

Dec 02, 2008

After you eat a burger and fries or other fat-filled meal, a protein produced by the liver may send a signal that fat is on the way, suggests a report in the December issue of the journal Cell Metabolism, a Cell Press public ...

Getting to the root of fatty liver disease

Apr 05, 2011

Researchers have identified a molecular switch that appears to be a common feature in the development of fatty liver disease. The discovery made in mice is consistent with data from human patients, suggesting ...

Recommended for you

Nearly 30% of world population is overweight: study

Nov 20, 2014

More than 2.1 billion people globally—or nearly 30 percent of the world's population—are now overweight or obese, with the figure set to rise further by 2030, according to a study published Thursday.

Report: Global obesity costs hits $2 trillion

Nov 20, 2014

The global cost of obesity has risen to $2 trillion annually—nearly as much as smoking or the combined impact of armed violence, war and terrorism, according to a new report released Thursday.

Small cash rewards pay off in weight loss plans

Nov 20, 2014

People who received small cash bonuses for their degree of participation in an Internet weight loss program shed more pounds than those who were not offered bonuses and they kept much of the weight off, according to a new ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.