The connection between adipose tissue and the brain is apparently more complex than previously thought, according to a study: Researchers have discovered that sensory neurons in fat send messages to the brain, which in turn serve to control developmental processes in the tissue. The scientists say the insights could show new ways of treating obesity or metabolic diseases.
As is well known, they form cushions on the body when they are particularly well supplied: the fat cells in mammals store excess energy and release it again when needed. In addition, hormones and signaling molecules related to metabolism and the feeling of hunger are formed in adipose tissue. In the history of human development, which was often marked by times of need, this system had a vital function. But in the affluent society, the formation of fatty tissue often becomes a problem. In addition, diseases such as diabetes, fatty liver, atherosclerosis and certain forms of obesity are associated with signaling disorders.
Until now, it was assumed that information was mainly conveyed via signaling molecules: hormones, which are passively transported in the blood, transmit information between the fatty tissue and the brain and ensure regulatory processes. However, it was already known that nerves extend into fatty tissue. However, it was previously assumed that this is not the category of so-called sensory neurons that transmit data to the brain. Instead, it has been suggested that the nerves in adipose tissue belong only to the sympathetic nervous system. This is part of the autonomic network that boosts fat burning during times of stress and physical activity.
Targeting the nerves of adipose tissue
However, it has so far been difficult to clarify the exact identity and function of the nerves in adipose tissue. This is because the methods normally used to study neurons don't work well in the depths of fatty tissue, where nerves are difficult to see or stimulate. But now the scientists led by Li Ye from the Scripps Research Institute in San Diego have used two new investigation methods and thus gained initial insights. The first is an imaging approach called HYBRiD. A sophisticated combination of substances is used that makes the fabric transparent while preserving certain structures. Using this method, the team was now able to follow the paths of the neurons that meander through the fatty tissue in mice.
They were able to discover that almost half of these neurons are not connected to the sympathetic nervous system, but to the so-called spinal ganglia. Their task is the transmission of information from sensory neurons from the periphery to the central nervous system and the brain. So there appear to be both sympathetic and sensory neurons in adipose tissue. To further unravel the role of the newly discovered nerve versions, the team then applied a second new technique they call retrograde vector optimized for organ tracing (ROOT). The method is based on the targeted destruction of specific neurons using selectively infecting viruses. In this way, the researchers turned off the sensory neurons in the adipose tissue of mice and then studied the effect.
A dual control system is emerging
The experiments made it clear that the sensory neurons play a role in developmental processes in adipose tissue. According to the researchers, when the brain stops receiving sensory information from adipose tissue, programs controlled by the sympathetic nervous system dominate. Specifically, the mice developed fat deposits with a particularly high proportion of brown fat cells. It is well known that increased combustion occurs in them. They are therefore also considered the “good fat”. In fact, the animals with switched off sensory neurons -- and a high proportion of sympathetic signals -- also had elevated body temperatures, the researchers report.
The results thus suggest that the two versions of neurons may have two opposing functions, with the sympathetic neurons being needed to turn on fat burning and brown fat production, and the sensory neurons being needed to turn off those programs. "These two types of neurons seem to act like an accelerator and a brake for fat burning," says Ye. It is therefore obvious that the system could be of importance for medicine. The scientists emphasize that it remains unclear exactly which messages are transmitted. They are therefore now planning to investigate further what the neurons perceive and whether there are similar cells in other internal organs of the body.
Source: Scripps Research Institute, Article: Nature, doi: 10.1038/s41586-022-05137-7