Yes, there is such a thing as obese mice—and recently they have helped scientists take a step toward reversing the ill effects of obesity in humans.
A study led at the University of Illinois identified a key molecular player in a chain of events 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.
Mir-34a, a micro-RNA, or a kind of biological regulator, occurs at higher than normal levels in the livers of obese animals and in humans with fatty liver disease. Researchers discovered that miR-34A complicates production of a key protein receptor, called beta-Klotho, needed for metabolic signaling in the liver, and hinders normal glucose uptake, glycogen and protein synthesis, and other metabolic activities.
Normally, beta-Klotho contributes to healthy liver function after a meal, says molecular and integrative physiology professor Jongsook Kim Kemper, who led the study. But in obesity, surging levels of miR-34a result in abnormally low levels of beta-Klotho.
“The downstream effect is more glucose in the blood, more fat in the liver,” she says.
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 says.
Their findings appear in the Proceedings of the National Academy of Sciences. American Diabetes Association supported this research.
