Scientists find brain mechanism that naturally combats overeating

March 28, 2019

Science Daily/Rockefeller University

Studying a brain region involved in memory, researchers discovered a set of neurons that help mice control their appetite.

Food is, generally speaking, a good thing. In addition to being quite tasty, it is also necessary for survival. That's why animals have evolved robust physiological systems that attract them to food and keep them coming back for more.

Now, research in mice reveals the existence of brain cells that have the opposite effect, curbing an animal's impulse to eat. Published in Neuron, the study shows that these cells also play a role in regulating memory, and are part of a larger brain circuit that promotes balanced eating.

The belly and the brain

Historically, researchers have thought of feeding as a visceral, instinctive process: An animal smells or sees an appealing snack and, without hesitation, proceeds to eat said snack. However, an increasingly detailed picture is now emerging in which mental processes inform animals' decision to either consume or refuse a meal.

A human, for example, may consider, "I'm supposed to be at brunch in 20 minutes, so I better save my appetite." Though other mammals may not have the equivalent internal monologue, there is reason to suspect that their eating habits do involve complex cognition. For example, research has shown that defects in the hippocampus -- a brain area involved in memory -- can alter feeding behavior, suggesting that past experiences influence an animal's attraction to food.

Building on this research, Estefania Azevedo, a postdoctoral associate in the lab of Jeffrey M. Friedman, recently identified a group of hippocampal cells, known as hD2R neurons, that become active whenever a mouse is fed. Collaborating with Paul Greengard, the Vincent Astor Professor, and Jia Cheng, a postdoctoral associate in his lab, the researchers also found that when these neurons were stimulated, mice ate less; and when they were silenced, they ate more. In short, hD2R neurons respond to the presence of food by deterring animals from eating that food.

Interpreting these findings, Azevedo says that, though animals usually benefit from eating the snacks in front of them, in some instances it is useful to exercise restraint. For example, if an animal has recently eaten, then searching for another meal is both unnecessary and risky, as foraging exposes animals to predators. The newly discovered neurons, it seems, help animals stop feeding when it no longer behooves them.

"These cells keep an animal from overeating," says Azevedo. "They appear to make eating less rewarding and, in that sense, are tuning the animal's relationship to food."

Everything in moderation

In the wild, you can't eat unless you know where to find food. Fortunately, brains are quite good at remembering the location of past meals: When an animal encounters sustenance in a particular locale, it makes a mental connection between the place and the food. To test how hD2R cells might affect these connections, Friedman and Azevedo stimulated the neurons as mice wandered around a food-filled environment. This intervention, they found, made mice less likely to return to the area in which food was previously located -- suggesting that hDR2 activation somehow diminishes meal-related memories.

"Mental connections between food and location are important for survival, and the strength of these connections is regulated by how rewarding an experience is," says Azevedo. "Because hD2R neurons affect an animal's relationship with food, it also ends up affecting these connections."

Further experiments showed that hD2R neurons receive input from the entorhinal cortex, which processes sensory information, and send output to the septum, which is involved in feeding. The first to identify this brain circuit, the researchers conclude that the neurons serve as a regulatory checkpoint between sensing food and eating food.

Together with analyses of other neural circuits, this research suggests that the brain has elaborate mechanisms for fine-tuning appetite: While some systems help an animal remember and find food, others restrain food intake.

"Our study shows that brain areas involved in cognitive processing and memory formation affect feeding behavior," says Azevedo. "So it is possible that, with training, people may be able to learn to change their relationship to food."

https://www.sciencedaily.com/releases/2019/03/190328150732.htm

In a nutshell: Walnuts activate brain region involved in appetite control

First-of-its-kind study reveals mechanism of walnuts' documented ability to decrease hunger

August 16, 2017

Science Daily/Beth Israel Deaconess Medical Center

Double-blind test bolsters observational data that walnuts promote feelings of fullness. Results provide a quantitative measure for testing other compounds' ability to control appetite, including potential medications for the treatment of obesity.

Packed with nutrients linked to better health, walnuts are also thought to discourage overeating by promoting feelings of fullness. Now, in a new brain imaging study, researchers at Beth Israel Deaconess Medical Center (BIDMC) have demonstrated that consuming walnuts activates an area in the brain associated with regulating hunger and cravings. The findings, published online in the journal Diabetes, Obesity and Metabolism, reveal for the first time the neurocognitive impact these nuts have on the brain.

"We don't often think about how what we eat impacts the activity in our brain," said the study's first author Olivia M Farr, PhD, an instructor in medicine in the Division of Endocrinology, Diabetes and Metabolism at BIDMC. "We know people report feeling fuller after eating walnuts, but it was pretty surprising to see evidence of activity changing in the brain related to food cues, and by extension what people were eating and how hungry they feel."

To determine exactly how walnuts quell cravings, Farr and colleagues, in a study led by Christos Mantzoros, MD, DSc, PhD hc mult, director of the Human Nutrition Unit at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School, used functional magnetic resonance imaging (fMRI) to observe how consuming walnuts changes activity in the brain.

The scientists recruited 10 volunteers with obesity to live in BIDMC's Clinical Research Center (CRC) for two five-day sessions. The controlled environment of the CRC allowed the researchers to keep tabs on the volunteers' exact nutritional intake, rather than depend on volunteers' often unreliable food records -- a drawback to many observational nutrition studies.

During one five-day session, volunteers consumed daily smoothies containing 48 grams of walnuts -- the serving recommended by the American Diabetes Association (ADA) dietary guidelines. During their other stay in the CRC, they received a walnut-free but nutritionally comparable placebo smoothie, flavored to taste exactly the same as the walnut-containing smoothie. The order of the two sessions was random, meaning some participants would consume the walnuts first and others would consume the placebo first. Neither the volunteers nor the researchers knew during which session they consumed the nutty smoothie.

As in previous observational studies, participants reported feeling less hungry during the week they consumed walnut-containing smoothies than during the week they were given the placebo smoothies. fMRI tests administered on the fifth day of the experiment gave Farr, Mantzoros and the team a clear picture as to why.

While in the machine, study participants were shown images of desirable foods like hamburgers and desserts, neutral objects like flowers and rocks, and less desirable foods like vegetables.

When participants were shown pictures of highly desirable foods, fMRI imaging revealed increased activity in a part of the brain called the right insula after participants had consumed the five-day walnut-rich diet compared to when they had not.

"This is a powerful measure," said Mantzoros. "We know there's no ambiguity in terms of study results. When participants eat walnuts, this part of their brain lights up, and we know that's connected with what they are telling us about feeling less hungry or more full."

This area of the insula is likely involved in cognitive control and salience, meaning that participants were paying more attention to food choices and selecting the less desirable or healthier options over the highly desirable or less healthy options. Farr and Mantzoros next plan to test different amounts, or dosages, of walnuts to see whether more nuts will lead to more brain activation or if the effect plateaus after a certain amount. This experiment will also allow researchers to test other compounds for their effect on this system.

Similar studies could reveal how other foods and compounds, such as naturally-occurring hormones, impact the appetite-control centers in the brain. Future research could eventually lead to new treatments for obesity.

"From a strategic point of view, we now have a good tool to look into people's brains -- and we have a biological read out." said Mantzoros. "We plan to use it to understand why people respond differently to food in the environment and, ultimately, to develop new medications to make it easier for people to keep their weight down."

https://www.sciencedaily.com/releases/2017/08/170816181259.htm