Since their discovery in the early 1990s and 2000s, micro-RNAs (miRNAs) have been implicated in a variety of human conditions. Most recently, researchers added yet another role of miRNAs in human health, this time in the regulation of weight and fat storage. As it turns out, a micro-RNA known as miR-181b is involved in influencing the risks for obesity and diabetes.
Micro-RNAs are simple short nucleotide sequences, usually 21-23 bases long, that act to silence gene expression. There are currently hundreds of known miRNAs, and most exist in unique locations inside the human body.
For the study, researchers at the Brigham and Women's Hospital (BWH) investigated whether specific miRNAs reside in adipose tissues, and whether these structures affect insulin resistance leading to obesity. To answer these questions, the team studied obese mice and found lower expression of miR-181b in adipose tissue endothelial cells.
They next wondered whether rescuing the expression of miR-181b to normal levels would improve insulin resistance. Indeed, when they administered a synthesized mimic of miR-181b to the obese mice, the researchers observed an improvement in glucose homeostasis and insulin sensitivity. Furthermore, inflammatory responses in fat tissues were also markedly improved when miR-181b levels were rescued.
Then using bioinformatics and gene profiling approaches, the team identified the target of miR-181b: a protein phosphatase enzyme called PHLPP2. In mice missing PHLPP2, researchers found the same biological effects as increasing miR-181b levels. These included improvement in glucose homeostasis and insulin sensitivity. PHLPP2 levels were also found at higher levels in endothelial cells from diabetic patients versus healthy controls.
The results demonstrate a direct involvement of this micro-RNA in the regulation of fat tissues during obesity. Moreover, it suggests that PHLPP2 could be a potential new target for treating related conditions in humans. "The beneficial role of this microRNA in obesity is likely the tip of the iceberg since excessive inflammation is a pervasive finding in a wide-range of chronic inflammatory diseases,” said Mark W. Feinberg, associate physician at BWH and senior study author.
Additional source: Brigham and Women's Hospital via EurekAlert!