Your brain and fat are communicating with each other, scientists discover
Our brain is actively surveying the fat.
A novel study led by a team from Scripps Research (previously known as The Scripps Research Institute) has demonstrated a new liaison between fat and the brain.
The study was published in Nature on August 31.
The brain does not simply respond to hormonal signals in the blood to regulate fat burning but can directly send messages to fat tissue and influence metabolic processes, the study says.
“The discovery of these neurons suggests for the first time that your brain is actively surveying your fat, rather than just passively receiving messages about it,” says co-senior author Li Ye, Ph.D., the Abide-Vividion Chair in Chemistry and Chemical Biology and an associate professor of neuroscience at Scripps Research.
“The implications of this finding are profound,” he also added.
“This is yet another example of how important sensory neurons are to health and disease in the human body,” says co-senior author and professor Ardem Patapoutian, Ph.D., who is also a Nobel laureate and a Howard Hughes Medical Institute investigator.
Before the recent study, the scientific world thought that adipose tissues were linked via the sympathetic nervous system. The research team had to create completely new imaging modalities to get the results of this research.
Two novel methods were used
Ye and his colleagues decided to use two novel methods to elucidate the study.
Firstly, the team used an imaging technique called HYBRiD to make mouse tissues transparent, allowing them to better track the paths of neurons as they snaked into adipose tissue.
The researchers discovered that nearly half of these neurons did not connect to the sympathetic nervous system but rather to the dorsal root ganglia, which is where all sensory neurons originate in the brain.
The team then used a second technique, which they called ROOT, for “retrograde vector optimized for organ tracing” to more thoroughly investigate the function of these neurons in adipose tissue.
ROOT allowed them to use a targeted virus to selectively eliminate small subsets of sensory neurons in the adipose tissue, and then they could see what happened.
From the spine to the fat tissue
The discovery of sensory neurons that branch out from the spine into fat tissue was the study’s major finding of the study. These sensory neurons have direct connections to the dorsal root ganglia.
“The discovery of these neurons suggests for the first time that your brain is actively surveying your fat, rather than just passively receiving messages about it,” said co-senior author Li Ye. “The implications of this finding are profound.”
Study abstract
Adipose tissues communicate with the central nervous system to maintain whole-body energy homeostasis. The mainstream view is that circulating hormones secreted by the fat convey the metabolic state to the brain, which integrates peripheral information and regulates adipocyte function through noradrenergic sympathetic output1. Moreover, somatosensory neurons of the dorsal root ganglia innervate adipose tissue2. However, the lack of genetic tools to selectively target these neurons has limited understanding of their physiological importance. Here we developed viral, genetic, and imaging strategies to manipulate sensory nerves in an organ-specific manner in mice. This enabled us to visualize the entire axonal projection of dorsal root ganglia from the soma to subcutaneous adipocytes, establishing the anatomical underpinnings of adipose sensory innervation. Functionally, selective sensory ablation in adipose tissue enhanced the lipogenic and thermogenetic transcriptional programs, resulting in an enlarged fat pad, enrichment of beige adipocytes, and elevated body temperature under thermoneutral conditions. The sensory-ablation-induced phenotypes required intact sympathetic function. We postulate that beige-fat-innervating sensory neurons modulate adipocyte function by acting as a brake on the sympathetic system. These results reveal an important role of the innervation by dorsal root ganglia of adipose tissues and could enable future studies to examine the role of sensory innervation of disparate interoceptive systems.
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