New research reveals neurons in the hippocampus that store memories of sugar and fat, influencing eating habits and metabolic health.
Can memory influence what and how much we eat? A groundbreaking study by the Monell Chemical Senses Center definitively answered this question with a resounding “Yes.” Led by Monell Associate Member Guillaume de Lartigue, PhD, the research team identified—for the first time—the brain’s food-specific memory system and its direct connection to overeating and diet-induced obesity.
Published in Nature Metabolism, the study highlights a specific group of neurons in the mouse brain that store memories related to sugar and fat, which significantly influence food consumption and body weight.
“In today’s world, we are constantly bombarded with advertisements and environmental triggers designed to remind us of pleasurable food experiences,” said Dr. de Lartigue. “What’s surprising is that we’ve pinpointed a specific population of neurons in the hippocampus that not only forms these food-related memories but also drives our eating behavior. This connection could have significant implications for body weight and metabolic health.”
These neurons encode memories of the spatial location of nutrient-rich foods, acting as a “memory trace,” particularly for sugar and fat. Silencing these neurons impairs an animal’s ability to recall sugar-related memories, reduces sugar consumption, and prevents weight gain, even when animals are exposed to diets that contribute to excessive weight gain. Conversely, reactivating these neurons enhances memory for food, increasing consumption and demonstrating how food memories influence dietary behavior.
These findings introduce two new concepts: first, evidence that specific neurons in the brain store food-related memories, and second, that these memories directly impact food intake. “While it’s no surprise that we remember pleasurable food experiences, it was long assumed that these memories had little to no impact on eating behavior,” said Dr. de Lartigue. “What’s most surprising is that inhibition of these neurons prevents weight gain, even in response to diets rich in fat and sugar.”
Memory’s Underappreciated Role
Memory is often overlooked as a key driver of food intake, but this study demonstrates a direct link between memory and metabolism. What sets this discovery apart from other studies related to memory is its implications for understanding metabolic health.
Deleting sugar-responsive neurons in the hippocampus of the animals not only disrupts memory but also reduces sugar intake and protects against weight gain, even when animals are exposed to high-sugar diets. This highlights a direct link between certain brain circuits involved in memory and metabolic health, which has been largely overlooked in the field of obesity research.
“Memory systems in the hippocampus evolved to help animals locate and remember food sources critical for survival,” said first author Mingxin Yang, a University of Pennsylvania doctoral student in the de Lartigue lab. “In modern environments, where food is abundant and cues are everywhere, these memory circuits may drive overeating, contributing to obesity.”
Specific, Yet Independent Circuits
Another key discovery is that food-related memories are highly specific. Sugar-responsive neurons encode and influence only sugar-related memories and intake, while fat-responsive neurons impact only fat intake. These neurons do not affect other types of memory, such as spatial memory for non-food-related tasks.
“The specificity of these circuits is fascinating,” said de Lartigue. “It underscores how finely tuned the brain is for linking food to behavior, ensuring animals can differentiate between various nutrient sources in their environment.” We have separate types of neurons that encode memory for foods rich in fat versus memory for foods rich in sugar. These separate systems presumably evolved because foods in nature rarely contain both fat and sugar, surmise the authors.
Implications for Treating Obesity
The study’s findings open new possibilities for addressing overeating and obesity. By targeting hippocampal memory circuits, it may be possible to disrupt the memory triggers that drive the consumption of unhealthy, calorie-dense foods.
“These neurons are critical for linking sensory cues to food intake,” said Dr. de Lartigue. “Their ability to influence both memory and metabolism makes them promising targets for treating obesity in today’s food-rich world.”
Reference: “Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation” by Mingxin Yang, Arashdeep Singh, Alan de Araujo, Molly McDougle, Hillary Ellis, Léa Décarie-Spain, Scott E. Kanoski and Guillaume de Lartigue, 15 January 2025, Nature Metabolism.
DOI: 10.1038/s42255-024-01194-6
This collaborative study was conducted with colleagues from the University of Pennsylvania and the University of Southern California and was supported by the National Institutes of Health and the American Heart Association.
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