Hunger alters the behavior of worms, and perhaps humans too •
We are probably all familiar with the way that hunger can change our behavior – make us grumpy, angry or less able to cope

Hunger alters the behavior of worms, and perhaps humans too

We are probably all familiar with the way that hunger can change our behavior – make us grumpy, angry or less able to cope. But the way in which signals from the gut are communicated to the brain and end up causing changes in behavior are not well understood. 

Now, scientists from the Salk Institute have investigated this topic, using lowly worms as a model to examine the molecular origins of behavioral changes in hungry individuals. They created a barrier of copper sulfate, a known worm repellent, and allowed tiny worms (Caenorhabditis elegans) the option of crossing it to access food on the other side.

“Animals, whether it’s a humble worm or a complex human, all make choices to feed themselves to survive. The sub-cellular movement of molecules could be driving these decisions and is maybe fundamental to all animal species,” said senior author Sreekanth Chalasani, associate professor in Salk’s Molecular Neurobiology Laboratory.

Chalasani and the team found that if worms were deprived of food for two to three hours, they were more willing to cross the toxic barrier to access the food than were well-fed worms. The researchers then used genetic tools and imaging techniques to establish whether molecules in the gut were signaling to the brain in ways that would explain this more risky behavior. 

The results, published today in PLOS Genetics, suggest that specific transcription factors, proteins that turn genes “on” and “off,” changed location in hungry animals.  Normally, transcription factors are found in a cell’s cytoplasm but move into the nucleus when activated, but the Salk scientists found that these transcription factors, known as MML-1 and HLH-30, move back to the cytoplasm in cells of the gut when a worm is hungry. 

When the scientists deleted these transcription factors, hungry worms stopped trying to cross the toxic barrier, indicating a central role for MML-1 and HLH-30 in controlling how hunger changes worm behavior.

In a subsequent experiment, the researchers also discovered that a protein called insulin-like peptide (INS-31) is secreted from the gut when MML-1 and HLH-30 are on the move. Neurons in the brain, in turn, make a receptor that might detect the INS-31secretions.

The authors summarize their findings as follows: in a worm deprived of food, the transcription factors MML-1 and HLH-30 move back to the cytoplasm of cells in the gut, which could promote the secretion of the protein called INS-31 from the gut cells. These INS-31 proteins then travel to, and bind to, receptors on neurons in the brain and this relays the information that food is needed. Worms then respond to the huger information by choosing appropriate behavior to access food, even if this involves taking risks.   

C. elegans are more sophisticated than we give them credit for,” said co-first author Molly Matty, a postdoctoral fellow in Chalasani’s lab. “Their intestines sense a lack of food and report this to the brain. We believe these transcription factor movements are what guide the animal into making a risk-reward decision, like traversing an unpleasant barrier to get to food.”

The researchers propose that such molecular mechanisms may also exist in humans and may change our behavior when we are hungry. They plan to undertake further research on the dynamic nature of these transcription factors and establish whether similar mechanisms operate in other animals, such as humans, to prioritize basic needs over comfort.

By Alison Bosman, Staff Writer

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