2026-02-24
When the hippocampus drives our cravings
Endocrinology and Metabolism
By Ana Espino | Published on February 24, 2026 | 3 min read
Obesity is a major public health challenge, largely promoted by a food environment rich in energy-dense products. The regulation of food intake no longer relies solely on classical homeostatic hunger and satiety circuits. It also involves complex cognitive mechanisms integrating memory, context, and environmental cues. Past experiences associated with foods shape dietary choices and can promote excessive consumption, independently of actual metabolic needs.
Traditionally, the hippocampus (HPC) is recognized for its central role in spatial and contextual memory. However, emerging evidence suggests that it also contributes to the control of feeding behavior. Previous studies have primarily highlighted an inhibitory role of the hippocampus in food intake, particularly in regulating meal size. Nevertheless, the precise neuronal mechanisms linking contextual memory to specific macronutrient preference remained insufficiently defined.
Published in January 2025 in Nature Metabolism, this study aimed to identify and characterize distinct neuronal ensembles within the dorsal hippocampus (dHPC) that are specifically activated by fat or sugar ingestion, and to determine their causal role in shaping dietary choice and modulating food intake.
The authors used murine models (C57BL/6J mice, 6–20 weeks old) combined with activity-dependent genetic tagging to identify dHPC neurons activated following ingestion of specific nutrients. Targeted stimulation and ablation approaches were employed to assess the causal role of these neuronal ensembles.
The results reveal the existence of spatially distinct neuronal populations within the dHPC activated either by fats or by sugars. Sugar-responsive neurons primarily encode the spatial memory of sugar location, forming a genuine sugar-specific appetitive engram. Their activation increases food intake, whereas their suppression impairs context-driven consumption.
In contrast, fat-responsive neurons enhance motivation and preference for fatty foods, modulating meal size and attraction to high-fat diets. Stimulation of these neurons specifically increases fat consumption, while their ablation reduces hypercaloric food intake and limits weight gain induced by an obesogenic diet.
The authors also demonstrate a causal role for the vagus nerve in transmitting post-ingestive signals to the hippocampus, suggesting the existence of a macronutrient-specific gut–brain circuit. These findings highlight an unexpected degree of hippocampal specialization in the control of food consumption.
Memory at the core of dietary choice
Obesity partly results from the interaction between metabolic signals and contextual food memory. This study sought to identify hippocampal circuits responsible for macronutrient-specific consumption.
The findings show that the dorsal hippocampus integrates sensory, mnemonic, and motivational information through distinct neuronal ensembles for sugars and fats. Sugar-sensitive neurons encode the contextual location of sweet foods, whereas fat-sensitive neurons amplify the motivation to consume them. This functional dissociation reveals the existence of specialized orexigenic circuits that may promote overconsumption in environments rich in food-related cues.
By identifying macronutrient-specific hippocampal circuits, this study opens new avenues for developing strategies targeting food memory and motivation in order to limit the consumption of obesogenic foods in modern environments. However, the results rely exclusively on animal models. Translation to humans requires further investigation, particularly through functional imaging and translational neuroscience approaches.
Read next: Liver, sugar, and pills: who's in control?
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
Obesity is a major public health challenge, largely promoted by a food environment rich in energy-dense products. The regulation of food intake no longer relies solely on classical homeostatic hunger and satiety circuits. It also involves complex cognitive mechanisms integrating memory, context, and environmental cues. Past experiences associated with foods shape dietary choices and can promote excessive consumption, independently of actual metabolic needs.
Traditionally, the hippocampus (HPC) is recognized for its central role in spatial and contextual memory. However, emerging evidence suggests that it also contributes to the control of feeding behavior. Previous studies have primarily highlighted an inhibitory role of the hippocampus in food intake, particularly in regulating meal size. Nevertheless, the precise neuronal mechanisms linking contextual memory to specific macronutrient preference remained insufficiently defined.
Published in January 2025 in Nature Metabolism, this study aimed to identify and characterize distinct neuronal ensembles within the dorsal hippocampus (dHPC) that are specifically activated by fat or sugar ingestion, and to determine their causal role in shaping dietary choice and modulating food intake.
Different neurons for sugar and fat ?
The authors used murine models (C57BL/6J mice, 6–20 weeks old) combined with activity-dependent genetic tagging to identify dHPC neurons activated following ingestion of specific nutrients. Targeted stimulation and ablation approaches were employed to assess the causal role of these neuronal ensembles.
The results reveal the existence of spatially distinct neuronal populations within the dHPC activated either by fats or by sugars. Sugar-responsive neurons primarily encode the spatial memory of sugar location, forming a genuine sugar-specific appetitive engram. Their activation increases food intake, whereas their suppression impairs context-driven consumption.
In contrast, fat-responsive neurons enhance motivation and preference for fatty foods, modulating meal size and attraction to high-fat diets. Stimulation of these neurons specifically increases fat consumption, while their ablation reduces hypercaloric food intake and limits weight gain induced by an obesogenic diet.
The authors also demonstrate a causal role for the vagus nerve in transmitting post-ingestive signals to the hippocampus, suggesting the existence of a macronutrient-specific gut–brain circuit. These findings highlight an unexpected degree of hippocampal specialization in the control of food consumption.
Memory at the core of dietary choice
Obesity partly results from the interaction between metabolic signals and contextual food memory. This study sought to identify hippocampal circuits responsible for macronutrient-specific consumption.
The findings show that the dorsal hippocampus integrates sensory, mnemonic, and motivational information through distinct neuronal ensembles for sugars and fats. Sugar-sensitive neurons encode the contextual location of sweet foods, whereas fat-sensitive neurons amplify the motivation to consume them. This functional dissociation reveals the existence of specialized orexigenic circuits that may promote overconsumption in environments rich in food-related cues.
By identifying macronutrient-specific hippocampal circuits, this study opens new avenues for developing strategies targeting food memory and motivation in order to limit the consumption of obesogenic foods in modern environments. However, the results rely exclusively on animal models. Translation to humans requires further investigation, particularly through functional imaging and translational neuroscience approaches.
Read next: Liver, sugar, and pills: who's in control?
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
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