Scientists at the Scripps Research Institute have discovered sensory neurons near the spine that carry messages from fat, or adipose tissue, to the brain. This discovery refutes the prevailing notion that circulating hormones are the only messengers between fat and brain cells. The results were published in the journal Nature (“The role of somatosensory innervation of adipose tissue”).
Nobel laureate, Howard Hughes Medical Institute researcher, neuroscience professor at Scripps University and study co-author Ardem Patapoutian, PhD said, “This is another example of how important sensory neurons are to health and disease in the human body.”
Li Ye, PhD, associate professor of neuroscience, Chair of Chemistry and Chemical Biology at Scripps and senior author of the study, said, “The discovery of these neurons suggests for the first time that your brain is actively monitoring your fat rather than just passively reporting on it.” to obtain. The implications of this realization are profound.”
Adipose tissue not only houses long-term stores of energy and releases it when needed, but also regulates hormones and signaling molecules that keep the brain informed of satiety and metabolism. Disruption of these crucial adipose tissue functions causes or contributes to several metabolic diseases, including diabetes, fatty liver disease, atherosclerosis and obesity.
Previously, scientists hypothesized that nerves that extend into adipose tissue are part of the autonomic sympathetic nervous system, which turns on fat-burning pathways during physical activity or stress. The lack of appropriate research techniques to study the innervation of adipose tissue has prevented researchers from identifying the nature and function of neurons in adipose cells. Traditional methods of visualizing or stimulating neurons in the brain or near the body’s surface do not work in fat cells.
A tissue-cleaning technique developed by Ye and his colleagues called HYBRiD uses solvents to dissolve opaque biomolecules like fat to make tissues transparent. In the current study, Yes’s team applied this protocol to track neurons that invade deep into adipose tissue. They found that nearly 50% was relayed not to the sympathetic ganglia that flank the spinal cord, but to the spinal ganglia (DRG), a collection of sensory neuron cell bodies. The technique allowed the team to visualize the entire axonal DRG projection from the cell body (soma) to the fat cells under the skin (subcutaneous adipocytes) and pinpoint their anatomical origins.
Next, to assess the function of these DRG neurons in adipose tissue, Ye’s team used a genetic technique developed by the previous team called ROOT (retrograde vector optimized for organ tracing). This allowed them to measure the consequences of removing selected small groups of sensory neurons in adipose tissue.
The study’s first author, Yu Wang, a graduate student in Ye and Patapoutian’s labs, said, “This research was really made possible by the way these new methods came together. When we started this project, there were no tools to answer these questions.”
Researchers discovered that experimentally removing sensory input from adipose tissue to the brain in mice triggers the formation of fat (lipogenesis) and increases the conversion of white fat to brown fat, leading to increased subcutaneous fat pads and elevated body temperatures in normal ambient conditions temperatures. Large amounts of brown fat are known to break down other fat and sugar molecules to generate heat.
These results suggest that sensory and sympathetic innervation may play opposing roles in adipose tissue—while sympathetic neurons turn on fat burning, sensory neurons trigger fat production. Ye said, “There is not just one universal instruction that the brain sends adipose tissue. It’s more nuanced than that. These two types of neurons act like an accelerator and brake for burning fat.”
Among the questions that remain unanswered is the nature of the messages to and from adipose tissue. Ye’s team is currently studying the sensory cues in fat cells more closely, looking for similar sensory neurons in visceral organs.