Ghrelin Receptor on Dopamine Neurons Drives Binge Eating of Fatty Food Without Hunger | Research

The takeaway

The ghrelin receptor on dopamine neurons is sufficient to drive binge-like high-fat eating and food anticipation in well-fed mice, but cannot explain ghrelin's general appetite-stimulating effects.

Binge eating restored, hunger response absent
Mice with ghrelin receptors only on dopamine neurons showed full binge-like high-fat eating but no general appetite increase from ghrelin

What the researchers found

DAT-GHSR mice (ghrelin receptor expression limited to dopamine neurons) showed: (1) c-Fos activation in dopamine-containing brain areas after ghrelin treatment, similar to wild-type mice; (2) normal anticipatory activity to scheduled high-fat diet exposure; (3) full binge-like high-fat intake comparable to wild-type mice. However, they did NOT show: increased food intake or locomotor activity in response to systemic or central ghrelin administration. GHSR-deficient mice showed impaired anticipatory activity and binge eating. Conclusion: GHSR in dopamine neurons is sufficient for hedonic high-fat eating but insufficient for ghrelin's homeostatic orexigenic effects.

Why it matters

Understanding that ghrelin acts on dopamine neurons specifically to drive pleasure-based eating of fatty food — independent of actual hunger — has profound implications for obesity and eating disorders. It suggests that blocking ghrelin's action on the reward system could reduce binge eating and cravings for unhealthy food without necessarily affecting normal hunger signaling.

How the study worked

Genetic approach using crossed reactivable GHSR-deficient mice with DAT-Cre mice to generate mice with ghrelin receptor expression exclusively on dopamine neurons (DAT-GHSR). Tested ghrelin-induced food intake, locomotor activity, c-Fos brain mapping, anticipatory activity to scheduled high-fat diet, and binge-like eating protocols. Compared DAT-GHSR, wild-type, and GHSR-deficient mice.

What this study cannot tell us

This is a mouse study using genetic manipulations that create an artificial situation (receptor expression only in one neuron type). The binge-eating protocols are standardized models that simplify complex human eating behaviors. The study used only male mice; sex differences in ghrelin signaling are well-documented. Translation to human eating disorders requires caution.

How to read the evidence

This is a sophisticated preclinical study using genetic tools to dissect specific neuronal contributions. The genetic specificity is a strength, but the artificial nature of selective receptor restoration and use of only male mice are limitations.

When this study was published

Published in 2020, this study contributes to the growing mechanistic understanding of how ghrelin drives reward-based eating, a field relevant to current GLP-1 drug research on appetite and addiction.

The bigger picture

The obesity epidemic is driven partly by hedonic eating — consuming palatable food for pleasure rather than caloric need. This study identifies a specific molecular mechanism: ghrelin receptor signaling in dopamine neurons. This dissection of ghrelin's dual role (homeostatic hunger vs hedonic reward) could guide the development of anti-obesity drugs that target reward-driven overeating without disrupting normal appetite regulation.

Questions still open

Could drugs that specifically block ghrelin signaling on dopamine neurons reduce binge eating without affecting normal appetite?
Does this ghrelin-dopamine mechanism explain why some people preferentially overeat high-fat foods?
Is the ghrelin receptor on dopamine neurons involved in the reward-based craving that drives substance use disorders as well?

Common questions

What's the difference between eating because you're hungry and eating because food tastes good?

Hunger-driven eating (homeostatic) is controlled by energy-sensing circuits in the brain. Pleasure-driven eating (hedonic) is controlled by reward circuits involving dopamine. This study shows ghrelin uses different brain pathways for each: dopamine neurons handle the pleasure/reward eating of fatty food, while other circuits handle actual hunger responses.

Could this explain why people binge eat even when they're not hungry?

Partially, yes. This study shows that ghrelin signaling on dopamine reward neurons is sufficient to drive binge-like eating of palatable food in well-fed mice. This suggests that ghrelin can trigger overconsumption purely through reward circuits, independent of caloric need — which mirrors the experience of people who binge eat despite not being physically hungry.

Read the original research

Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice.

Psychoneuroendocrinology, 119, 104718

View on PubMed ↗Publisher’s paper ↗

Citation

Cornejo, María Paula; Barrile, Franco; Cassano, Daniela; Aguggia, Julieta Paola; García Romero, Guadalupe; Reynaldo, Mirta; Andreoli, María Florencia; De Francesco, Pablo Nicolás; Perello, Mario. (2020). Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice.. Psychoneuroendocrinology, 119, 104718. https://doi.org/10.1016/j.psyneuen.2020.104718