GHSR Signaling Controls High-Fat Binge Eating Independent of Ghrelin and LEAP2
Background
The growth hormone secretagogue receptor (GHSR) is a key player in regulating appetite and energy balance, primarily known for its interaction with ghrelin, a potent hunger-stimulating hormone. Another peptide, LEAP2, acts as an endogenous antagonist, inhibiting ghrelin's effects at GHSR. While the ghrelin-GHSR axis is well-established in appetite regulation, the precise role of GHSR signaling in binge eating, particularly high-fat food consumption, and whether its effects are always mediated through circulating ghrelin and LEAP2 levels, remains unclear.
Results
Treatment with the GHSR antagonist, GHSR-X, significantly reduced high-fat food intake in the binge eating model. This reduction was specific to high-fat intake, as total caloric intake from standard chow remained unchanged. Importantly, plasma levels of both ghrelin and LEAP2 showed no significant alterations in response to GHSR-X treatment (p>0.05 for both), indicating an independent mechanism. Body weight gain was also attenuated by 15% in the treated group (p<0.05).
Why It Matters
This study highlights that GHSR signaling can directly influence high-fat food intake in a binge eating context, independent of circulating ghrelin and LEAP2 levels. This suggests a novel, direct role for GHSR in the brain's reward pathways or other central mechanisms governing food choice and consumption. Targeting GHSR with specific antagonists could represent a promising therapeutic strategy for treating binge eating disorder and related forms of obesity, potentially offering an alternative to therapies that modulate ghrelin directly. Future research should focus on identifying the specific neural circuits involved and progressing to Phase II human trials.