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

add to favorites email to friend print save as pdf

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

Optimal gestational weight gain in obese moms may vary

Jan 23, 2015

(HealthDay)—For some obese women, gestational weight gain (GWG) below that recommended in the current guidelines may be advised to reduce the risk of certain adverse pregnancy outcomes, according to research ...

Obesity more expensive to treat than smoking

Jan 19, 2015

(HealthDay)—Annual health care expenses are substantially higher for smokers and the obese, compared with nonsmokers and people of healthy weight, according to a report published online Dec. 24 in Public He ...

A fatty acid used to decode weight control

Jan 15, 2015

Obesity can be described as an excess of fat leading to metabolic diseases and adipose tissue has a pivotal role in obesity and its related complications.

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.