Novel Study Proves That Our Brains Can Directly Communicate With Fat Cells

For many years scientists thought that a person's fat, also known as adipose tissue, sent information about stress and metabolism to the brain through hormones passively floating through the blood.

But a study published in Nature on August 31 has revealed a brand-new relationship between fat and the brain. The study was led by a team of researchers from Scripps Research (formerly known as The Scripps Research Institute)

The study found that to control fat burning; the brain does more than only react to hormonal signals in the blood. Brains can, however, directly communicate with fat tissue and affect metabolic processes.

From the spine to the fat tissue

The key finding of the study was the identification of sensory neurons that protrude into adipose tissue from the spine.


For the first time, according to Li Ye, Ph.D., “the discovery of these neurons raises the prospect that the human brain actively examines your fat rather than just receiving information about it passively.” Li Ye is an associate professor of neuroscience and holds the Abide-Vividion Chair in Chemistry and Chemical Biology at Scripps Research.

“The consequences of this discovery are enormous,” he continued.

Understanding this brain-fat communication could be beneficial in the future for the growing population of people dealing with obesity and related health issues like diabetes and heart disease.


Collaborating Ye’s comment, Professor Ardem Patapoutian, Ph.D., co-senior author, said, “This is yet another example of how important sensory neurons are to health and disease in the human body.” Professor Patapoutian is a Howard Hughes Medical Institute researcher and a Nobel laureate.

The system adds another layer to the already complicated interplay

The system adds yet another layer to the already complicated interplay between our diet, genes, environments, and microbiome- all contribute to our levels of these important insulating energy stores.

Although it has long been established that mammals contain an abundance of neurons, these nerves were only recently connected to the mammalian sympathetic nervous system in animal models.


The sympathetic nervous system governs our body’s automatic, unconscious responses like increasing our heart rate or dilating our eyes.

Sympathetic Nervous System
sympathetic nervous system by under CC BY-SA 4.0

They encourage the breakdown of fat for usage during exercise, hunger, and other stressors.

Although these signals traveling from the brain to our fat have been shown, it is still unknown what signals are traveling in the opposite direction through our nerves.


Two new methods were used for the study

The sympathetic nervous system was previously thought to be the pathway via which adipose tissue was related in the scientific community. 

Li Ye and his colleagues decided to use two completely new imaging modalities to elucidate the study and get the research results.

To solve the technological challenges of accessing neurons deeply embedded in our bodies’ fat without damaging them, the team created a new imaging approach called HYBRiD and a focused cell manipulation method called ROOT.


1.      HYBRiD

The researchers designed an imaging approach called HYBRiD (hydrogel-reinforced cleared mammalian tissue). It allows the researchers to follow the neuron paths as they wound into adipose tissue because it made mouse tissues translucent.

HYBRiD removes the molecules that give tissues their opacity using solvents, leaving behind transparent tissues that are intact in their original shapes.


The resulting visualizations allowed Li Ye and his colleagues to find that nearly almost half of the adipose neurons did not connect to the sympathetic nervous system. Rather, they connect to the sensory nervous system, where all sensory neurons originate in the brain.


2.      ROOT

To better probe the role of these neurons in adipose tissue, the team used a second technique they called ROOT (retrograde vector optimized for organ tracing) to more thoroughly investigate the function of these neurons in adipose tissue.


They were able to observe what happened thanks to ROOT, which allowed researchers to apply a targeted virus to selectively eradicate small subsets of the sensory neurons in the adipose tissue.

Mice with higher levels of brown fat were shown to have more body fat when the sensory neuron signal was lost.

Additionally, the mice’s body temperatures were higher, which makes sense given that brown fat aids in the body’s conversion of sugar and other lipids into heat.


Yu Wang, a graduate student in both the Ye and Patapoutian labs and the paper’s first author, adds that the way these new technologies came together “truly made this research viable. At the outset of this endeavor, there weren’t any tools available to address these questions.”

What the experiments revealed

The research showed that programs related to the conversion of white fat to brown fat are activated excessively in fat cells when the brain’s sympathetic nervous system is not receiving sensory input from adipose tissue. 

This results in a larger-than-normal fat pad with particularly high levels of brown fat, which breaks down other fat and sugar molecules to produce heat. The animals with blocked sensory neurons and excessive sympathetic transmission did, in fact, have higher body temperatures.

1024px Brown fat cell
Brown fat cell by under CC BY-SA 4.0

According to the research, sympathetic neurons are necessary for the brown fat formation and fat burning, but sensory neurons are needed to switch these programs off. This implies that sympathetic and sensory neurons might play conflicting roles.

It “reveals that the human brain does not provide a single set of instructions to the adipose tissue,” says Li. It’s more nuanced than that; these two types of neurons serve as throttle and a brake for different aspects of fat burning.”

Research conclusion

The scientists concluded their newly discovered system of sensory neurons must work to control the signals from the sympathetic nervous system that tell the body to burn fat by turning them down or off.


“This demonstrates that the brain’s instructions to adipose tissue are not universal,” says Li.

“That’s not how it works. For the purpose of burning fat, these two varieties of neurons function as a gas pedal and a brake.”

As is the case with comparable neurons identified inside other organs, the team speculates that these nerves may also play a critical role in interoception, the awareness of sensations coming from within our bodies. However, they haven’t looked into this and are eager to learn more about this system.


Featured image credit: Brain nervous system by

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