Researchers find a brain circuit in mice that plays a role in overindulging in high-calorie foods.
There is a large bag of chips in our lap; we are not hungry, but we manage to eat every last one of them.
Many of us will be familiar with this scenario, but humans are not the only mammal with a drive to overeat high-calorie foods.
In evolutionary terms, if an animal finds a food source high in nutrients, it makes sense to eat as much as possible; in the wild, starvation is an ever-present danger.
Today, we have access to energy-dense foods wherever we look; in fact, it can be challenging to find foods that are not packed with sugar and fat.
We have evolved to find these types of food delicious — and food companies know it.
Homeostatic vs. hedonic feeding
So-called homeostatic feeding occurs when an animal eats until it has satiated its hunger and restored its energy levels.
Hedonic feeding, on the other hand, describes an animal’s drive to eat more than it needs if the food source is particularly nutrient-dense and delicious.
Although our highly evolved brains can usually wield enough self-control to override these primal urges, we are not always successful.
This life-saving mechanism might now play a part in the rise of obesity and associated conditions.
As new study co-author Prof. Thomas Kash, Ph.D., points out, “There’s just so much calorically dense food available all the time now, and we haven’t yet lost this wiring that influences us to eat as much food as possible.”
Recently, researchers from the University of North Carolina Health Care in Chapel Hill took a detailed look at this phenomenon in rodents’ brains. They recently published their findings in the journal Neuron.
In recent years, researchers looking for ways to reduce obesity have investigated the mechanisms involved in homeostatic feeding. To date, this approach has not led to successful interventions.
More recently, however, scientists — including those involved in the new study — have looked to hedonic feeding for answers.
Nociceptin and overeating
Previous studies have shown that nociceptin, a peptide consisting of 17 amino acids that functions as a neurotransmitter, might play a part in hedonic feeding.
Other research has demonstrated that nociceptin receptors make little difference to homeostatic feeding, but that they appear to play a role in hedonic feeding. Drug companies are of course interested in creating “anti-binging drugs,” but scientists are a long way from achieving that.
However, Prof. Kash and team have moved one step closer by pinning down the neural circuit that seems to be most heavily involved in hedonic eating in mice.
To drill down to a specific circuit, they engineered mice that produce a fluorescent marker-tagged nociceptin. This made it easier to visualize the cells involved in nociceptin circuits.
Many circuits in the brain utilize nociceptin, but the researchers identified one particular circuit that lit up when the mice binged on energy-dense foods. This circuit has projections to other parts of the brain that help regulate feeding, so it seems to be a strong candidate.
This particular circuit originates in the central nucleus of the amygdala, a part of the brain that plays a vital role in an animal’s response to emotional stimuli.
The authors believe that “this is the first study to ascribe specific hedonic feeding actions to a subpopulation of [central amygdala] neurons.”
Removing the overeating circuit
In follow-up experiments, the scientists deleted around half of the neurons that produce nociceptin in the circuit. They found that this reduced levels of binge eating.
They gave the mice access to standard chow and high-calorie food, alternatively. With these neurons silenced, the mice significantly reduced their intake of high-calorie food and resisted diet-induced obesity. Their consumption of standard chow remained consistent.
“Scientists have studied the amygdala for a long time, and they’ve linked it to pain and anxiety and fear, but our findings here highlight that it does other things too, like regulate pathological eating.”
Prof. Thomas Kash, Ph.D.
This is an intriguing discovery, but it is just the beginning of a long process; scientists will need to carry out much more research to fully understand how this new mechanism fits into the bigger picture.
“Our study is one of the first to describe how the brain’s emotional center contributes to eating for pleasure,” explains first study author J. Andrew Hardaway, Ph.D.
“It adds support to the idea that everything mammals eat is being dynamically categorized along a spectrum of good/tasty to bad/disgusting, and this may be physically represented in subsets of neurons in the amygdala.”
“The next major step and challenge,” he adds, “is to tap into these subsets to derive new therapeutics for obesity and binge eating.”
The complex story of nociceptin
Since its discovery in 1995, nociceptin has received a great deal of attention from researchers.
Aside from its potential to moderate hedonic eating, scientists are investigating it for the treatment of depression and alcohol abuse and testing its potential use as a pain reliever.
Although this molecule has great potential to moderate a range of behaviors and states, this variety also produces difficulties: Nociceptin is prevalent in the central nervous system, so how does one make a treatment specific enough to alter only the behavior of interest?
It is also worth mentioning the drawbacks of using a mouse model to study binge eating. Although the rodent model has provided a wealth of information relevant to the control of feeding in humans, binge eating is a different case.
For instance, a review titled ‘Food addiction and binge eating: Lessons learned from animal models’ states that “[rodent] models cannot reproduce all social context that influence human eating behavior; neither some psychological aspects, such as sense of lack of self-control, blame, or guilt.”
The author of another review on the topic writes that “there is currently not a general consensus in terms of which criteria a rodent model should fulfill to be considered accurate for the study of neurobiological aspects of binge eating episodes.”
As ever, scientists will continue delving into the world of brain circuit-induced overeating until they reach an answer or the trail runs cold. For now, watch this space.
