Fluorescence helps show relationship between the brain and metabolism

Using genetically encoded fluorescent sensors in a C. elegans model could determine how quickly the intestine burns fat.

Content Dam Bow Online Articles 2016 02 Witham Srinivasan Web

Seeking to determine that oxygen-sensing neurons have a role in metabolism, scientists at The Scripps Research Institute (TSRI; La Jolla, CA) used genetically encoded fluorescent sensors in a C. elegans model to determine how quickly the intestine burns fat. They found that fat reserves in the intestine could also influence the strength of the fat-burning signal from the nervous system.

Supriya Srinivasan, a TSRI assistant professor and senior author of the study, wondered what other neuronal functions fat can modulate based on whether or not oxygen-sensing neurons change their activity based on how much fat there is in an animal. The findings raise the possibility of a similar mechanism in humans that may be dysregulated in diseases such as Bardet-Biedl Syndrome, in which patients with extreme obesity appear to have dysfunctional sensory perception. However, the oxygen sensors in humans are not yet known.

Content Dam Bow Online Articles 2016 02 Witham Srinivasan Web
Scripps Research Institute assistant professor Supriya Srinivasan (right) authored the new study with research associate Emily Witham and colleagues. (Photo courtesy of The Scripps Research Institute)

Food intake is known as an important regulator of metabolism. For example, if consumption of food is low, the body burns fat and makes up for missing nutrients. But there is growing evidence that fat burning is more complicated than previously thought. Recent research has shown that the nervous system circuits involved in regulating metabolism are distinct from those regulated by feeding behavior.

In the new study, the researchers screened a family of genes known to be important in sensory perception. By deleting these genes one at a time in C. elegans, the researchers found that two of these genes were connected to fat metabolism. Interestingly, one of the genes was only expressed in a handful of neurons previously shown to sense oxygen levels in a worm’s environment. Using genetically encoded fluorescent sensors, the researchers found that the amount of fat reserves could affect neuronal activity in response to oxygen.

The researchers believe this connection in C. elegans might exist as a way of sensing food availability. The worms eat bacteria that consume oxygen, so slightly lower levels of oxygen, compared with normal atmospheric oxygen, signal that a meal is nearby. In a follow-up experiment, the researchers found that when oxygen levels were high—indicating no nearby food—the worms would ramp up fat burning. When oxygen levels were slightly lower—indicating nearby food—the worms did not burn fat as quickly. The worms seemed to sense a meal was coming, so there was no need to switch to emergency fat-burning mode yet.

To their surprise, the researchers found the intestine can also communicate back to the neurons. When fat reserves dipped too low, the neuronal signal to burn fat was dampened. This led the researchers to predict that the intestine was signaling the neurons to lower their activity when there was not enough fat available to be burned.

While it is too soon to say if the insights on fat burning translate to humans, Srinivasan says the findings open new doors to research on metabolism and the mysteries of cross-tissue communication. She says the next step in this research is to identify the molecule that delivers the messages between the intestines and the neurons at play in this study.

Full details of the work appear in the journal Cell Reports; for more information, please visit http://dx.doi.org/10.1016/j.celrep.2016.01.052.

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