Blood has many biomarkers that can reveal the health of most organs in the body. Now Danish researchers have developed a new method to interpret the messages of these microscopic biomarkers. Among other things, researchers can see how weight-loss surgery changes the health of blood vessels and the immune response.
Obesity is associated with the risk of developing arteriosclerosis, non-alcoholic fatty liver disease, cardiovascular diseases, insulin resistance and many other diseases, all of which greatly strain many major organs.
Now Danish researchers have developed a method using a simple blood test that may indicate how healthy the body’s organs are.
The discovery means that, in the future, doctors can test a person’s blood after, for example, weight-loss surgery thereby enabling them to clinically assess whether the person’s organs are getting healthier as the weight is lost.
“We can determine whether the person’s health inside the body changes after this surgery or whether it only affects a person’s weight,” explains Aase Handberg, Clinical Professor, Aalborg University Hospital, a researcher behind the new study.
The research was published recently in Nutrition & Metabolism.
Tiny messengers communicate between organs
Microvesicles are tiny messengers that communicate between cells.
Basically, microvesicles are tiny bulges (vesicles) on the body’s cells that are shed as small pellets into the blood and other bodily fluids.
Microvesicles are then transported around the body with the blood, bringing many types of molecules from organ to organ. These molecules can include cellular surface proteins or tiny fragments of RNA that can regulate the activity of genes.
In this sense, the microvesicles communicate between parts of the body. For example, microvesicles can be secreted from fat cells and then bind to cells in the liver. The microvesicles thus provide the liver with information about the fat cells.
If the microvesicles contain tiny fragments of regulating RNA, the RNA may also influence the liver cells and thereby the liver’s function.
“Microvesicles comprise a fantastic communication system within the body. We also know that microvesicles exist in all bodily fluids, including blood, tears, sweat and urine,” says Aase Handberg.
Using microvesicles to see inside the body
In this new research project, Aase Handberg and her colleagues discovered how they could decode the microvesicles and use them as biomarkers. They developed a method for using a simple blood sample to directly detect microvesicles from various organs and thus theoretically use them to determine the health of the liver, blood vessels, immune system, kidneys or pancreas.
If a person has developed non-alcoholic fatty liver disease, the unhealthy accumulation of fat in liver cells, circulating microvesicles reflect this, according to Aase Handberg.
The reason why microvesicles can be used as tiny biomarkers is because these are minute fragments of the organs themselves. They are like tiny microbiopsies of individual cells.
“By testing blood, we can theoretically say something about all the body’s organs. So far we have been able to do this for the liver, skeletal muscles, immune cells and the lining of blood vessels. This has major perspectives, especially for the liver, because many diseases are associated with the liver,” says Aase Handberg.
A membrane protein associated with the risk of cardiovascular disease, obesity and arteriosclerosis
This study is the latest development in Aase Handberg’s research, which began 10 years ago with a membrane protein called CD36.
CD36 is on the surface of cells and imports fatty acids into the cells. It thus plays a role in developing obesity, arteriosclerosis, cardiovascular diseases and other diseases because increasing the uptake of fat in the cells means more fat in the organs.
Many years ago, Aase Handberg showed that the concentration of CD36 in the blood can be measured and that a higher concentration means an increased risk of type 2 diabetes and other complications of obesity.
“Basically, we hypothesize that when a person consumes excess calories, the body has to deposit them somewhere. The body can deposit the extra calories in fat tissue on hips and thighs, but these have limited capacity, so if excess calorie intake continues, the body then begins to deposit the fat in the organs. This is where CD36 has a role,” says Aase Handberg.
Antibodies identify specific microvesicles
Aase Handberg has developed a method to identify monocyte microvesicles and endothelial microvesicles in a blood test by using specific antibodies that recognize these types of cells.
Monocytes are the cells that become macrophages, the scavengers of the immune response, and endothelial cells are the cells lining the blood vessels. Both types of cells are very active in developing arteriosclerosis and metabolic syndrome, a precursor of type 2 diabetes.
By using antibodies against CD36, the researchers then discovered how many CD36 proteins cells have on their surface.
The concentration of CD36 in the microvesicles enabled the researchers to determine the extent to which the body deposits fat and activates monocytes and endothelial cells, and this can be directly associated with the health of the body in relation to obesity.
“The wider perspective is to use microvesicles as biopsies because tissue cannot be sampled from many parts of the body. In this study, we primarily examined CD36, but we could also have investigated glucose-transporting molecules, which tell us about the efficiency of glucose metabolism or a membrane protein that is a biomarker for a disease,” explains Aase Handberg.
Weight-loss surgery is also good for the organs
The researchers tested the blood of severely obese people before and after gastric bypass surgery.
When the researchers examined the blood tests, they discovered that trial subjects who had undergone the surgery also had a generally reduced concentration of CD36 in the microvesicles from monocytes and endothelial cells.
According to Aase Handberg, this indicates that this surgery not only affects weight but also positively influences the underlying mechanisms that damage the health of severely obese people. These included the accumulation of fat in the organs and general inflammation in the body’s immune cells and endothelial cells, which promotes arteriosclerosis.
“The microvesicles show that things are improving. Thus, analysing microvesicles also enables us to determine whether something is wrong or whether to focus on specific health-related areas after weight-loss surgery. For example, if the concentration of CD36 in the liver or in the monocytes or endothelial cells does not decline, then these areas should be in focus in relation to diet and medication in the future,” says Aase Handberg.
“Bariatric surgery reduces CD36-bearing microvesicles of endothelial and monocyte origin” has been published in Nutrition and Metabolism. Researchers from the Novo Nordisk Foundation Center for Basic Metabolic Research have participated in the project.