In work for finding new targets to fight obesity, the researchers have identified a new pathway for regulating the fat formation. They have found that this mechanism works in mammals to control the creation of fat. The journal “Genes & development” has presented this finding.
The miR-26 family controls the levels of FBXL19 protein
Obesity is a worldwide problem. That acts as a major risk factor for many chronic diseases. These diseases may include diabetes type 2, NAFLD, cardiovascular disease, cancer, and stroke.
The researchers have discovered that the loss of a family of microRNAs can lead to a significant increase in fat formation. On the contrary, the overexpression of the miR-26 family of miRNAs can prevent weight gain.
The molecular mechanisms that control how and where fat tissue will build up in the body are vital to understanding the development of obesity. But still, the researchers haven’t completely understood the molecular pathways that affect the number and size of fat cells in the body.
The results of the study have suggested that, in mice fed with a high-fat diet, overexpression of miR-26 family plays a role in regulating the fat formation. And strongly protects them against weight gain.
Further study has shown that the mir-26 family regulates the levels of FBXL19 protein. That is essential for the production of new fat cells. Previously, no link was identified between this protein and obesity or fat formation. So, this finding was quite unexpected.
In mammals, a high-fat diet – loaded with calories, can lead to an expansion in the existing fat cells. Additionally, it can also result in the formation of new fat cells from stem-like progenitor cells. The process of fat storage is highly regulated in adult mammals.
Overexpression of the miR-26 family may prevent an increase in weight
One of the features of obesity is the unregulated expansion of white fat tissue. In the case of surplus calories, this fat tissue does more than storing energy. It can also play an important part in metabolic regulation.
It does so by secreting lipids and the signaling proteins. These influence pathways controlling blood sugar balance, appetite, and immune responses. The earlier studies have shown the important role of the miR-26 family as regulators of insulin sensitivity and suppressors of cancer.
But, the comprehensive functions of this family have remained a mystery. To some extent, this was due to the difficulty of removing or knocking out, all three miR-26 family producing genes, to study their functions.
To overcome this technical difficulty, the research team has used the CRISPR/Cas9 technique. It is a gene-editing technique that can remove all three genes from the mouse genome that are encoding miR-26.
The team found that mice lacking miR-26 developed normally in their early life. But, in early adulthood, there was a two to three times increase in white fat tissue. This result was present even after consuming a normal diet.
To further analyze the importance of these miRNAs in regulating the fat formation, the team has used a different genetically engineered mouse line. That has an excess miR-26 production.
After having a high-fat diet, normal mice showed a significant increase in weight. Where the fat content raised to 40% of the overall body mass. On the contrary, mice with excessive miR-26 were strongly resistant to this weight gain.
These mice also showed lower blood lipid and sugar levels when compared with controls. This study has identified a new pathway for regulating fat metabolism. And a deeper understanding of this pathway can help in developing new therapies to treat obesity.