Mice lacking beta-endorphin showed reduced binge eating and food reward, while mice lacking enkephalin showed no change, identifying beta-endorphin as the key opioid peptide driving these behaviors.
β-endorphin, not enkephalinIdentified as the specific opioid peptide responsible for binge eating and food reward via mu-opioid receptors
What the researchers found
Using knockout mice, the study distinguished the roles of two opioid peptides:
- Mu-opioid receptor (MOR) knockout mice: reduced binge eating on high-fat diet re-exposure, diminished food devaluation after 7-day HFD exposure, and failed to show conditioned food reward
- Beta-endorphin (β-END) knockout mice: reduced binge eating and diminished food reward, but normal food devaluation
- Enkephalin (ENK) knockout mice: no significant changes in binge eating, food reward, or food devaluation
All genotypes showed normal initial food intake for both regular chow and high-fat diet, indicating these peptides specifically affect binge/reward behaviors rather than basic hunger.
Why it matters
Binge eating disorder affects millions of people and has limited pharmacological treatment options. Identifying beta-endorphin as the specific opioid peptide driving binge eating and food reward, distinct from enkephalin, provides a precise molecular target for developing treatments that could reduce pathological overeating without broadly disrupting the opioid system.
How the study worked
Male knockout mice lacking either mu-opioid receptors, beta-endorphin, or enkephalin were compared with their wildtype littermates. They were tested for regular and high-fat diet intake, binge eating (measured on re-exposure to HFD after abstinence), food reward (conditioned place preference with HFD), and food devaluation (reduced chow intake after HFD exposure).
What this study cannot tell us
The study was conducted in male mice only; female mice, who have higher rates of binge eating disorders in humans, were not tested. Genetic knockouts eliminate the peptide from birth, which may trigger compensatory mechanisms not present in adult pharmacological interventions. The high-fat diet model may not fully capture the complexity of human binge eating disorder.
How to read the evidence
This is a well-controlled preclinical study using knockout mice with appropriate wildtype littermate controls. The use of three different knockout lines to dissect the pathway is rigorous, though results are in mice only.
When this study was published
Published in 2025 in Progress in Neuro-Psychopharmacology & Biological Psychiatry, this is a recent contribution to understanding the peptide basis of binge eating behavior.
The bigger picture
The endogenous opioid peptide system has long been implicated in eating disorders and food addiction. This study provides the clearest evidence yet that beta-endorphin, not enkephalin, is the critical peptide mediating the rewarding properties of food and binge eating. This specificity could guide the development of more targeted therapies for binge eating disorder.
Questions still open
- Would a selective beta-endorphin antagonist reduce binge eating in humans without the side effects of broad opioid receptor blockers?
- Do female mice show the same beta-endorphin-dependent binge eating pattern, given sex differences in eating disorders?
- Could beta-endorphin levels serve as a biomarker for binge eating disorder severity?
Common questions
What is the connection between opioid peptides and binge eating?
Could blocking beta-endorphin help treat binge eating disorder?
Read the original research
The involvement of the endogenous opioid system in binge eating, food devaluation and food reward in mice.
Progress in neuro-psychopharmacology & biological psychiatry, 142, 111539
Citation
Era, Iffat Hasnin; Hamid, Abdul; Lutfy, Kabirullah. (2025). The involvement of the endogenous opioid system in binge eating, food devaluation and food reward in mice.. Progress in neuro-psychopharmacology & biological psychiatry, 142, 111539. https://doi.org/10.1016/j.pnpbp.2025.111539