Biology

The Hunger Pains: Mice genetically engineered to not feel them

Scientists have found the remaining piece of the neurochemistry puzzle that causes hunger, and created mice who don't feel it (Photo: Shutterstock)
Scientists have found the remaining piece of the neurochemistry puzzle that causes hunger, and created mice who don't feel it (Photo: Shutterstock)

Hunger pains are the bane of any dieter's existence, kicking in even when skipping a single meal and goading the sufferer to indulge their desire for food. Controlling hunger is now better understood as neuroscientists tease apart why we (well, our model mouse cousins) feel hunger. Mind-bendingly, the same researchers have used genetic therapies to create feelings of satiety where none would otherwise exist.

A collaboration of scientists at Beth Israel Deaconess Medical Center at Harvard, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Health located the unknown factor in the neurochemical pathway that drives hunger and eating. To test their theories, mice were genetically engineered to respond to artificial cues to turn off and on an instinct that is one of the most primal known to man or beast.

Referring to this pathway as a wiring diagram is not far from the truth, with chemical cues setting up electrical exchanges that feed the activity of other cells downstream. If you are hungry while reading this, it's also an alphabet soup of acronymns for proteins, genes, and laboratory techniques.

Switches (hunger neurons) in the brain detect low energy and release signals (AgRP peptides), which block a switch that lets you feel full. Teasing out the final switch from chemical clues allowed researchers to locate the small group of neurons in the hypothalamus (the PVH MC4R neurons) that are responsible for the release of chemicals that create the feeling of satiety.

However, this is where the research starts feeling a little eye-wideningly bizarre, or promising, all in the same bite. To confirm the PVH MC4R hypothesis, scientists constructed genetically modified mice with newly engineered artificial switches, a technique that lets researchers use otherwise inert molecules to turn the PVH MC4R neurons on and off at will.

When these modified mice had their PVH MC4R neurons turned off, they could no longer feel full and frantically consumed food even if they had met their caloric needs for the day. Conversely, when the neurons were artificially turned on, otherwise hungry mice would not eat food, suggesting that they could not feel hunger.

To further tease out what portion of the brain is involved in receiving the satiety signals, mice were genetically engineered with a new trigger. This involved a technology called optigenetics, which saw blue laser light being delivered to the brain activate the specific neural connection scientists wanted to explore.

The mice could now "choose" whether to feel full or not, simply by activating the blue light. Hungry mice had the option to move into one room where a computer would activate the light fed via an optical fiber into their brains. Instant gratification! No more feelings of hunger. Similarly, moving into the opposite room would deactivate the connection, the pathways would be blocked from releasing the right molecules, and hunger would return.

As expected, unmodified mice had no preference which room to spend time in, but the modified mice greatly preferred to stay in the room with the laser.

And yes, if you read this entire article only wanting to know if this could work to help with dieting, the researchers anticipate that this discovery could lead to therapies to reduce food consumption in humans while avoiding any punitive hunger pangs.

"Turning on the PVH-MC4R satiety neurons had the same effect as dieting but because it directly reduced hunger drive it did not cause the gnawing feelings of discomfort that often come with dieting," explains Bradford Lowell, one of the co-senior authors of the paper.

The team's findings were originally published in Nature Neuroscience.

Source: Beth Israel Deaconess Medical Center

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2 comments
Tricksterinator
Hunger pangs, as opposed to "pains", is probably more appropriate in the title. While normal hunger certainly causes a sensation, it is not pain.
pmshah
Lookout America ! Find alternative use for corn and corn syrup.