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Scientists thought they understood how our brains keep track of our body fat levels: by monitoring fat-related hormones in the blood.
But in a new study, the researchers found a whole extra messaging system.
It turns out we have an entire sensory system dedicated to relaying messages from our adipose tissue (adipose tissue) to our brain.
“The discovery of these neurons suggests for the first time that your brain is actively exploring your fat, and not just passively receiving messages about it,” says Li Ye, a neuroscientist at the Scripps Research Institute.
“The implications of this discovery are profound.”
Understanding this system could one day help the growing number of people struggling with being overweight and related health problems like heart disease and diabetes.
This adds another layer to the already complex interplay between our genes, environment, diet, and microbiome that all contribute to our levels of these important insulating energy stores.
While researchers have long known that mammalian fat is riddled with neurons, these nerves have been linked in animal models to the mammalian sympathetic nervous system—the system that controls our body’s automatic, unconscious responses, such as increasing our heart rate or widening our eyes.
They promote the breakdown of fat for use during physical activity, hunger and other stresses.
But while these messages from the brain to our fat have been established, questions remain about what kind of signaling goes back in our nerves.
“When we first started this project, there were no tools to answer these questions,” explains Scripps Research Institute neuroscientist Yu Wang.
So Wang and his colleagues have developed tools, including a new imaging technique called HYBRiD and a targeted cell manipulation technique called ROOT, to overcome the technical challenges of penetrating neurons deep in our body’s fat tissue without damaging them.
Researchers have developed HYBRiD (purified mammalian tissue reinforced with hydrogel) so that large, intact tissue samples can be carefully examined. It uses solvents to remove the molecules that give tissues their opacity, leaving transparent tissues in their original configuration.
The addition of fluorescent proteins that target specific tissue types allows researchers to clearly display structures of interest.
The resulting visualizations allowed Wang and his team to clearly see that almost half of the fat neurons are connected not to the sympathetic nervous system, but to the sensory nervous system.
They then used ROOT (a retrograde vector optimized for organ tracking) to selectively target and kill different subsets of neurons in mice.
Loss of signal from sensory neurons led to an increase in fat in mice, especially those with high levels of brown fat. The mice also had higher body temperatures, which makes sense since brown fat helps our bodies convert other fats and sugars into heat.
The researchers concluded that their newly identified system of sensory neurons must be regulating signals from the sympathetic nervous system, instructing the body to burn our fat—reducing or turning them off.
“This tells us that there is no universal instruction that [the] the brain sends adipose tissue,” says Lee.
“It’s more nuanced: these two types of neurons act like a gas pedal and a fat-burning brake.”
The team suspects that these nerves may also play a crucial role in interoception — the perception of sensations coming from our body, as happens with similar neurons found inside other organs. But they have yet to explore this, and they are keen to explore this system further.
This study was published in Nature.