A new study published in the Proceedings of the National Academy of Sciences reveals that people who suffer from obesity-associated metabolic abnormalities, such as type II diabetes and fatty liver disease, have higher levels of a micro-RNA which can be blocked to reverse some of the pathology caused by its actions.
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 fatty liver disease. 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 glucose uptake, glycogen and protein synthesis 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 effects are dramatic. Slices of liver tissue 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.