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A direct line of communication identified between fat tissue and the brain

Researchers have discovered sensory nerve cells that send messages from fat tissue to the brain in mice. This finding challenges the conventional notion that circulating hormones in the blood are the sole messengers sending information related to stress and metabolism between fat tissue and brain cells.

In mammals, fat tissue stores energy (calories) and releases this energy when the body needs it. Fat tissue also regulates hormones and signaling molecules that update the brain on fullness, hunger, and metabolism. Disruption of these critical functions can contribute to several diseases including diabetes, obesity, and fatty liver disease. Researchers have known that nerve cells contact fat tissue. However, they suspected that they were part of a network of nerves responsible for the body’s “fight-or-flight” response that activates fat-burning pathways during stress and physical activity—not sensory nerve cells that carry data directly to the brain. Until now, a lack of suitable laboratory tools and techniques prevented scientists from identifying the function of nerve cells contacting fat tissue. The team of researchers leading this study developed new techniques to overcome these obstacles.

First, they used an imaging technique they had recently developed that turned fat tissue transparent so they could visualize the nerve cells that extend into the tissue. Surprisingly, in experiments in male mice, they discovered that nearly half of the nerve cells were not part of the fight-or-flight response network, but rather connected to an area of the brain where sensory cells originate. Next, the team used a genetic tool, developed previously and that they optimized, to analyze the function of the sensory nerve cells by selectively removing these cells within the fat tissue. The experiments demonstrated that destroying sensory input from fat tissue to the brain in mice results in elevated body temperatures and the generation of “beige fat,” a type of fat tissue that breaks down other fat molecules to produce heat. These results suggest that the two types of nerve cells extending into fat tissue, cells in the fight-or-flight network and sensory cells, have opposing functions: the former act as a “gas pedal” for burning fat, and the latter act as the “brake”. When the brake was removed, a response reminiscent of fight-or-flight was activated (fat-burning, body temperature increase).

These findings fill an important knowledge gap on how the brain regulates different fat tissue functions, highlighting the importance of this newly discovered avenue of brain-body communication. Future research could lead to new therapeutic strategies to treat obesity and other metabolic diseases.

Wang Y, Leung VH, Zhang Y, …Ye L. The role of somatosensory innervation of adipose tissues. Nature 609: 569-574, 2022.

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