New link between brain and fat-burning circuit

New link between brain and fat-burning circuit

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's 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 a roundworm called C. elegans, cues picked up from the environment--specifically, the sensing of oxygen by the brain--determined how quickly the intestine burns fat. Surprisingly, this communication worked both ways, and fat reserves in the intestine could also influence the strength of the fat-burning signal from the nervous system.

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.

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.

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. It was as if these worms switched to emergency mode and broke open the reserve rations.

When oxygen levels were slightly lower--indicating nearby food--the worms didn't 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 wasn't enough fat available to be burned.

While it's too soon to say if the insights on fat burning translate to humans, Srinivasan said the findings open new doors to research on metabolism and the mysteries of cross-tissue communication. 

http://www.scripps.edu/news/press/2016/20160211srinivasan.html

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