Beyond the Covid-19 pandemic, there is a large-scale epidemic that continues to go unnoticed in the eyes of most. It’s about the obesitya public health problem that already suffers from more than half of the population in our country, as the data shows: 61.5% of Spaniards have extra kilosas 39.9% of the people surveyed are overweight and 21.6% are obese, according to data from the Spanish Obesity Society (Seedo).
Given this scenario, there is an unknown that for many years has hovered over the scientific community and that now begins to have an answer: What does fat tell our brain? For years, it was assumed that the hormones passively floating in the blood were a person’s way of fat, called adipose tissue, being able to send information related to stress and metabolism to the brain. Now, scientists at Scripps Research have turned this intuition on its head and shown in the prestigious magazine «Nature» that newly identified sensory neurons carry a stream of messages from adipose tissue to the brain.
“The discovery of these neurons suggests for the first time that your brain is actively examining your fat, rather than passively receiving messages about itsaid co-senior author Li Ye, PhD, Abide-Vividion Chair in Chemistry and Chemical Biology and Associate Professor of Neuroscience at Scripps Research. “The implications of this finding are profound,” acknowledges the research team. Specifically, “this is yet another example of how important sensory neurons are to health and disease in the human body”insists co-senior author Professor Ardem Patapoutian, PhD, who is also a Nobel laureate and a Howard Hughes Medical Institute investigator.
In mammals, Adipose tissue stores energy in the form of fat cells, and when the body needs energy, it releases those stores. It also controls a host of hormones and signaling molecules related to hunger and metabolism. In diseases like diabetes, fatty liver disease, atherosclerosis, and obesity, energy storage and signaling often fail.
A new type of neuron
Researchers have long known that the nerves extend into fat tissue, but they suspected they were not sensory neurons that carry data to the brain. Instead, most hypothesized that the nerves in fat belonged primarily to the sympathetic nervous system, the network responsible for our fight-or-flight response, which activates fat-burning pathways during times of stress and physical activity. Attempts to clarify the types and functions of these neurons have been difficult; methods used to study neurons closer to the surface of the body or in the brain do not work well in deep adipose tissue, where the nerves are difficult to see or stimulate. Ye and his colleagues developed two new methods that allow them to overcome these challenges. First, an imaging approach called HYBRiD turned mice tissues transparent and allowed the team better trace the pathways of neurons as they meandered through adipose tissue. The researchers discovered that almost half of these neurons did not connect to the sympathetic nervous system, but to the dorsal root ganglia, an area of the brain where all sensory neurons originate.
To further investigate the role of these neurons in adipose tissue, the group turned to a second new technique, which they called ROOT, for “retrograde vector optimized for organ tracking.” Specifically, ROOT allowed them to selectively destroy small subsets of sensory neurons in adipose tissue using a specific virus and then observe what happened. “This research was really made possible by the way these new methods came together,” confirms Yu Wang, a graduate student in the Ye and Patapoutian labs and first author of the new paper.
“When we started this project, there were no tools to answer these questions,” the researchers acknowledge. The experiments revealed that when the brain does not receive sensory messages from adipose tissue, the programs activated by the sympathetic nervous system (related to the conversion of white fat to brown fat) become overactive in fat cells, resulting in larger fat than the normal with especially high levels of brown fat, which breaks down other fat and sugar molecules to produce heat. In fact, animals with blocked sensory neurons and high levels of sympathetic signaling had increased body temperatures.
Thus, the findings suggest that sensory neurons and sympathetic neurons may have two opposing functions, with sympathetic neurons needed to turn on fat burning and brown fat production, and sensory neurons needed to turn off these programs. “This tells us that there is no single instruction that the brain sends adipose tissue,” says Li, who insists that “these two types of neurons are acting as an accelerator and a brake to burn fat”. The team doesn’t yet know exactly what messages sensory neurons transmit to the brain from fat tissue, just that the connections and communications are key to keeping fat healthy. They are planning future research into what the neurons detect and whether similar cells exist in additional internal organs.
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