Scientists have discovered a specific group of brain cells that create memories of meals, encoding not just what food was eaten but when it was eaten. The findings, published today in Nature Communications, could explain why people with memory problems often overeat and why forgetting about a recent meal can trigger excessive hunger and lead to disordered eating.

During eating, neurons in the ventral hippocampus region of the brain become active and form what the team of researchers call "meal engrams" -- specialized memory traces that store information about the experience of food consumption. While scientists have long studied engrams for their role in storing memories and other experiences in the brain, the new study identified engrams dedicated to meal experiences.

"An engram is the physical trace that a memory leaves behind in the brain," said Scott Kanoski, professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences and corresponding author of the study. "Meal engrams function like sophisticated biological databases that store multiple types of information such as where you were eating, as well as the time that you ate."

Distracted eating implications

The discovery has immediate relevance for understanding human eating disorders. Patients with memory impairments, such as those with dementia or brain injuries that affect memory formation, may often consume multiple meals in quick succession because they cannot remember eating.

Furthermore, distracted eating -- such as mindlessly snacking while watching television or scrolling on a phone -- may impair meal memories and contribute to overconsumption.

Based on the experiment's findings, meal engrams are formed during brief pauses between bites when the brain of laboratory rats naturally survey the eating environment. These moments of awareness allow specialized hippocampal neurons to integrate multiple streams of information.

Kanoski said it can be assumed a human's brain would undergo a similar phenomenon. When someone's attention is focused elsewhere -- on phone or television screens -- these critical encoding moments are compromised. "The brain fails to properly catalog the meal experience," said Lea Decarie-Spain, postdoctoral scholar at USC Dornsife and the study's first author, "leading to weak or incomplete meal engrams."

Mechanism of 'meal memories'

The research team used advanced neuroscience techniques to observe the brain activity of laboratory rats as they ate, providing the first real-time view of how meal memories form.

The meal memory neurons are distinct from brain cells involved in other types of memory formation. When researchers selectively destroyed these neurons, lab rats showed impaired memory for food locations but retained normal spatial memory for non-food-related tasks, indicating a specialized system dedicated to meal-related information processing. The study revealed that meal memory neurons communicate with the lateral hypothalamus, a brain region long known to control hunger and eating behavior. When this hippocampus-hypothalamus connection was blocked, the lab rats overate and could not remember where meals were consumed.

Eating management implications

Kanoski said the findings could eventually inform new clinical approaches for treating obesity and weight management. Current weight management strategies often focus on restricting food intake or increasing exercise, but the new research suggests that enhancing meal memory formation could be equally important.

"We're finally beginning to understand that remembering what and when you ate is just as crucial for healthy eating as the food choices themselves," Kanoski said.

In addition to Kanoski, other study authors include Lea Decarie-Spain, Cindy Gu, Logan Tierno Lauer, Alicia E. Kao, Iris Deng, Molly E. Klug, Alice I. Waldow, Ashyah Hewage Galbokke, Olivia Moody, Kristen N. Donohue, Keshav S. Subramanian, Serena X. Gao, Alexander G. Bashaw and Jessica J. Rea of USC; and Samar N. Chehimi, Richard C. Crist, Benjamin C. Reiner and Matthew R. Hayes from the University of Pennsylvania's Perelman School of Medicine; and Mingxin Yang and Guillaume de Lartigue from the Monell Chemical Senses Center; and Kevin P. Myers from the Department of Psychology at Bucknell University.

The study was supported by a Quebec Research Funds Postdoctoral Fellowship (315201), an Alzheimer's Association Research Fellowship (AARFD-22-972811), a National Science Foundation Graduate Research Fellowship (DK105155), and a National Institute of Diabetes and Digestive and Kidney Diseases grant (K104897).

The study found that oleic acid, a monounsaturated fat associated with obesity, causes the body to make more fat cells. By boosting a signaling protein called AKT2 and reducing the activity of a regulating protein called LXR, high levels of oleic acid resulted in faster growth of the precursor cells that form new fat cells.

"We know that the types of fat that people eat have changed during the obesity epidemic. We wanted to know whether simply overeating a diet rich in fat causes obesity, or whether the composition of these fatty acids that make up the oils in the diet is important. Do specific fat molecules trigger responses in the cells?" said Michael Rudolph, Ph.D., assistant professor of biochemistry and physiology at the University of Oklahoma College of Medicine and member of OU Health Harold Hamm Diabetes Center.

Rudolph and his team, including Matthew Rodeheffer, Ph.D., of Yale University School of Medicine and other collaborators at Yale and New York University School of Medicine, fed mice a variety of specialized diets enriched in specific individual fatty acids, including those found in coconut oil, peanut oil, milk, lard and soybean oil. Oleic acid was the only one that caused the precursor cells that give rise to fat cells to proliferate more than other fatty acids.

"You can think of the fat cells as an army," Rudolph said. "When you give oleic acid, it initially increases the number of 'fat cell soldiers' in the army, which creates a larger capacity to store excess dietary nutrients. Over time, if the excess nutrients overtake the number of fat cells, obesity can occur, which can then lead to cardiovascular disease or diabetes if not controlled."

Unfortunately, it's not quite so easy to isolate different fatty acids in a human diet. People generally consume a complex mixture if they have cream in their coffee, a salad for lunch and meat and pasta for dinner. However, Rudolph said, there are increasing levels of oleic acid in the food supply, particularly when access to food variety is limited and fast food is an affordable option.

"I think the take-home message is moderation and to consume fats from a variety of different sources," he said. "Relatively balanced levels of oleic acid seem to be beneficial, but higher and prolonged levels may be detrimental. If someone is at risk for heart disease, high levels of oleic acid may not be a good idea."

A sugar compound found in sea cucumbers can effectively block Sulf-2, an enzyme that plays a major role in cancer growth, according to a University of Mississippi-led study published in Glycobiology.

"Marine life produces compounds with unique structures that are often rare or not found in terrestrial vertebrates," said Marwa Farrag, a fourth-year doctoral candidate in the UM Department of BioMolecular Sciences.

"And so, the sugar compounds in sea cucumbers are unique. They aren't commonly seen in other organisms. That's why they're worth studying."

Farrag, a native of Assiut, Egypt, and the study's lead author, worked with a team of researchers from Ole Miss and Georgetown University on the project.

Human cells, and those of most mammals, are covered in tiny, hairlike structures called glycans that help with cell communication, immune responses and the recognition of threats such as pathogens. Cancer cells alter the expression of certain enzymes, including Sulf-2, which in turn modifies the structure of glycans. This modification helps cancer spread.

"The cells in our body are essentially covered in 'forests' of glycans," said Vitor Pomin, associate professor of pharmacognosy. "And enzymes change the function of this forest - essentially prunes the leaves of that forest.

"If we can inhibit that enzyme, theoretically, we are fighting against the spread of cancer."

Using both computer modeling and laboratory testing, the research team found that the sugar - fucosylated chondroitin sulfate - from the sea cucumber Holothuria floridana can effectively inhibit Sulf-2.

"We were able to compare what we generated experimentally with what the simulation predicted, and they were consistent," said Robert Doerksen, professor of medicinal chemistry. "That gives us more confidence in the results."

Unlike other Sulf-2 regulating medications, the sea cucumber compound does not interfere with blood clotting, said Joshua Sharp, UM associate professor of pharmacology.

"As you can imagine, if you are treating a patient with a molecule that inhibits blood coagulation, then one of the adverse effects that can be pretty devastating is uncontrolled bleeding," he said. "So, it's very promising that this particular molecule that we're working with doesn't have that effect."

As a marine-based cancer therapy, the sea cucumber compound may be easier to create and safer to use.

"Some of these drugs we have been using for 100 years, but we're still isolating them from pigs because chemically synthesizing it would be very, very difficult and very expensive," Sharp said. "That's why a natural source is really a preferred way to get at these carbohydrate-based drugs."

Unlike extracting carbohydrate-based drugs from pigs or other land mammals, extracting the compound from sea cucumbers does not carry a risk of transferring viruses and other harmful agents, Pomin said.

"It's a more beneficial and cleaner resource," he said. "The marine environment has many advantages compared to more traditional sources."

But sea cucumbers - some variants of which are a culinary delicacy in the Pacific Rim - aren't so readily abundant that scientists could go out and harvest enough to create a line of medication. The next step in the research is to find a way to synthesize the sugar compound for future testing.

"One of the problems in developing this as a drug would be the low yield, because you can't get tons and tons of sea cucumbers," Pomin said. "So, we have to have a chemical route, and when we've developed that, we can begin applying this to animal models."

The interdisciplinary nature of the scientific study, which featured researchers from chemistry, pharmacognosy and computational biology, underscored the importance of cross-disciplinary collaboration in tackling complex diseases like cancer, Pomin said.

"This research took multiple expertise - mass spectrometry, biochemistry, enzyme inhibition, computation," Pomin said. "It's the effort of the whole team."

This work is based on material supported by the National Institutes of Health grant nos. 1P20GM130460-01A1-7936, R01CA238455, P30CA51008 and S10OD028623.