Cracking the fat and organ "conversation" mechanism can help treat obesity

Cracking the fat and organ "conversation" mechanism can help treat obesity

March 09, 2017 Source: 澎湃 News Network

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Recently, researchers have confirmed through experiments that fat cells can “talk” to organs by transmitting molecular information and managing genes in distant organs such as the liver. This finding will be of great significance in the treatment of type 2 diabetes and obesity.

The discovery was published in the February 15 issue of the British journal Nature. Thomas Thomou, a researcher at Harvard Medical School and the Joslin Diabetes Center, led his team to confirm that adipose tissue can release tiny molecules to communicate with body organs.

Specifically, fat will "send" the miRNA, the messenger carrying information, and reach the distant organs through the exogenous "communication ship" and regulate it. The role of fat in regulating metabolism is higher than scientists thought before, which opens up new research ideas for communication between cells. At the same time, because of the ability to develop gene therapy using fat cells, this new finding also provides new options for the treatment of some diseases, such as type 2 diabetes and obesity.

Robert Freishtat, a children's health system from Washington, DC, is a pediatrician and a researcher on metabolic diseases such as diabetes and obesity, but he is not involved in the latest study. According to Frestatte, scientists have long known that fat is associated with the development of various diseases, but does not fully understand how adipose tissue affects distant organs and their functioning.

Previously, scientists only knew that fat releases hormones and reminds the brain to manage appetite, but recent research suggests that there may be another “signal difference” in adipose tissue: a substance called miRNA (microRNA), which is a genetic material. A small piece in the middle.

What are miRNAs and exosomes?

Explain miRNA, starting with the working process of the living body. DNA is the "Commander" responsible for guiding biological development and vital functioning, but specific biological functions are performed by proteins. Therefore, DNA needs to be first transcribed into RNA and then translated into proteins by RNA. This process is called gene expression, in which RNA acts as an intermediary.

miRNA is a non-coding single-stranded RNA molecule involved in the regulation of gene expression after transcription of DNA into RNA. In addition to this "task", some miRNA fragments are released into the bloodstream through the exosomes and into the circulatory system.

Exosomes are lipid-encapsulated structures with a diameter of 50-200 nm, and almost all types of cells can produce and release exosomes.

The capsular exosomes are like a "communication ship". After being secreted by the cells, they are loaded with some substances, circulated in body fluids such as blood, and enter another cell to unload these substances. After completing the communication "mission", the exosomes can be swallowed up by other cells. miRNA is one of the substances that can be incorporated into exosomes in order to prevent miRNAs from being degraded and stable.

Part of the miRNA in the exosomes comes from fat

To better understand how miRNAs "work" for adipose tissue, in the first experiment, the researchers removed key miRNA processing enzymes from experimental mouse adipocytes, which meant that the mice could no longer generate miRNAs. It was found that mice that had removed key miRNA processing enzymes were unable to efficiently produce glucose compared to normal mice, and more importantly, the total number of miRNAs in exosomes also decreased.

On this basis, the researchers transferred normal mouse fat to mice with key miRNA processing enzymes removed, and the results showed that the number of miRNAs in the exosomes was repaired in the circulatory system of the modified mice. This result indicates that many of the miRNAs in the circulatory system are derived from fat.

miRNAs in fat "ride" exosomes, "arriving" distant organs

To explore whether fats use miRNAs to communicate with other body tissues, the researchers designed a second experiment. In a group of normal mice, the researchers engineered brown fat cells to produce human miRNAs that were loaded into exosomes. Another group of normal mice was engineered with liver cells to generate fluorescent molecular targets for "detection" of human miRNAs.

The researchers then injected exosomes from the first group of mice (modified brown fat cells) into a second group of mice (modified liver cells). The results showed that the fluorescence of the liver cells of the second group of mice was significantly decreased because the human miRNAs in the exosomes of the first group of mice acted on the fluorescent targets and inhibited the formation of target cells. This confirms that adipose tissue can communicate with the liver through miRNAs in exosomes while managing gene expression.

Researchers say the findings not only provide a new perspective, but also explain what the path of human tissue communication is, and also provide a new way to change disease status.

Tommo and his team plan to continue exploring the characteristics of their respective miRNAs in other different organizations to confirm that other substances besides the miRNA are encased in the exosomes.

For Frestatte, this new research effort is exciting and complements the distance between mouse models and human studies. He said that this is a huge project, we have just opened the veil of exosomes, just began to study how they manage the body process.

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