Study reveals new link between brain and fat-burning circuit

February 11, 2016, The Scripps Research Institute
Scripps Research Institute Assistant Professor Supriya Srinivasan (right) authored the new study with Research Associate Emily Witham and colleagues. Credit: The Scripps Research Institute.

A new study in animal models, led by scientists at The Scripps Research Institute (TSRI), is the first to show that oxygen sensing in the brain has a role in metabolism and sensing an organism's internal state.

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 implications for this are interesting," said TSRI Assistant Professor Supriya Srinivasan, who was senior author of the new study. "If oxygen-sensing neurons change their activity based on how much fat there is in an animal, what other neuronal functions can fat modulate?"

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 study was published February 11, 2016 by the journal Cell Reports.

A Metabolic Mystery

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.

"That implies that our metabolism is not a simple consequence of ," said Srinivasan.

But if food intake isn't the only player controlling metabolism, what else is?

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 . Interestingly, one of the genes was only expressed in a handful of neurons previously shown to sense in a worm's environment.

"A lightbulb went off in my head—there could be a connection between sensing oxygen and burning fat," said Srinivasan.

Using genetically encoded fluorescent sensors, the researchers found that the amount of fat reserves could affect neuronal activity in response to oxygen.

"This is an interesting, previously unknown role for these neurons," said TSRI Research Associate Emily Witham, who was first author of the new study.

Got Oxygen? Burn Fat

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 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.

"We think that this is a self-preservation system, which prevents a deleterious fat-burning signal from the neurons in conditions of depleted reserves," said Witham.

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

"We think a hormone-like factor is secreted," said Srinivasan. "We're chasing down that signal."

Explore further: Researchers uncover how common white fat can be turned into energy-burning brown fat in humans

More information: "C. elegans Body Cavity Neurons are Homeostatic Sensors That Integrate Fluctuations In Oxygen Availability And Internal Nutrient Reserves," Cell Reports, 2016.

Related Stories

Researchers uncover how common white fat can be turned into energy-burning brown fat in humans

August 4, 2015
Researchers from The University of Texas Medical Branch at Galveston have discovered, for the first time in humans, that the widely reviled energy storing white fat can be turned into an energy burning brown fat that uses ...

Could our brain instruct our bodies to burn more fat?

January 15, 2015
By uncovering the action of two naturally occurring hormones, scientists may have discovered a way to assist in the shedding of excess fat.

Fish oil helps transform fat cells from storage to burning

December 17, 2015
Researchers have found that fish oil transforms fat-storage cells into fat-burning cells, which may reduce weight gain in middle age.

Taste buds lining up as the first line of defence against obesity

January 14, 2016
Training our taste buds to be more sensitive to the taste of fat could be key in the battle to curb the world's growing obesity problem.

From brain, to fat, to weight loss

September 24, 2015
Weight is controlled by the hormone leptin, which acts in the brain to regulate food intake and metabolism. However, it was largely unknown until now, how the brain signals back to the fat tissue to induce fat breakdown. ...

Researchers discover how body's good fat tissue communicates with brain

March 27, 2015
Brown fat tissue, the body's "good fat," communicates with the brain through sensory nerves, possibly sharing information that is important for fighting human obesity, such as how much fat we have and how much fat we've lost, ...

Recommended for you

Advanced sensor to unlock the secrets of the brain

April 24, 2018
Researchers have announced the development of a state-of-the-art sensor that can for the first time detect signalling molecules, called cytokines, which operate in the living brain. Cytokines in the brain are secreted by ...

New cell therapy aids heart recovery—without implanting cells

April 23, 2018
Heart disease is a major global health problem—myocardial infarction annually affects more than one million people in the U.S. alone, and there is still no effective treatment. The adult human heart cannot regenerate itself ...

DOR protein deficiency favors the development of obesity

April 20, 2018
Obesity is a world health problem. Excessive accumulation of fat tissue (adipose tissue) increases the risk of cardiovascular disease, hypertension, diabetes and some types of cancer. However, some obese individuals are less ...

Researchers identify blood biomarkers that may help diagnose, confirm concussions

April 20, 2018
Researchers from the University of California, Irvine, Georgetown University and the University of Rochester have found that specific small molecules in blood plasma may be useful in determining whether someone has sustained ...

Stem-cell technology aids 3-D printed cartilage repair

April 20, 2018
Novel stem-cell technology developed at Swinburne will be used to grow the massive number of stem cells required for a new hand-held 3-D printer that will enable surgeons to create patient-specific bone and cartilage.

Enduring cold temperatures alters fat cell epigenetics

April 19, 2018
A new study in fat cells has revealed a molecular mechanism that controls how lifestyle choices and the external environment affect gene expression. This mechanism includes potential targets for next-generation drug discovery ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.